Resumo em Inglês:
Abstract Ayahuasca (AYA) is a psychedelic beverage with therapeutic potential for many mood and anxiety disorders. Although there are some preclinical studies, no published reports have tested the behavioral effects of AYA gavage in animal models. This investigation aimed to characterize the behavior of Wistar rats after acute ingestion of AYA for 40 min in the open field test (OFT). The sample consisted of three experimental groups treated with different dosages of AYA (125, 250, or 500 mg kg-1) and a control group. Each group consisted of 10 participants. After gavage, the number of crossings of the OFT grid lines, latency to enter the central area of the device, grooming frequency, and time spent in the central perimeter of the device were immediately evaluated. Analyses were based on one-way ANOVA and a linear-regression mixture model for longitudinal data. AYA intake did not interfere with habituation. The 500 mg kg-1 group showed a decrease in the time spent in the center of the device and in the number of crossings compared to the control group in the last 10 min. These results suggest that gavage with AYA did not interfere with the results, and the behavioral effects were perceived only between 30 and 40 min after gavage. Taken together, the results indicate that three aspects should be considered in OFT studies of AYA acute effects: the moment when the observation starts, the observation period, and the AYA dosage.Resumo em Inglês:
Abstract Poloxamer is a biocompatible polymer that has already been approved by the US FDA for multiple applications. Poloxamer itself has many grades and functional categories that enable the improvement of both physicochemical and biological properties of drugs. In this minireview, the functional properties of poloxamer for physicochemical modification, such as solubility and stability, and biological response modification, such as neuroprotection, cell apoptosis, efflux pump modification, membrane cell modification, and cellular uptake, are discussed to provide a broader understanding to assist the development of poloxamer-based formulations.Resumo em Inglês:
Abstract Because it promotes the lightening of pigment spots, tyrosinase inhibition is one of the mechanisms of depigmenting cosmetic products. Considering the adverse effects produced by synthetic depigmenting actives, the search for new therapeutic options is desirable, and plant extracts are possible candidates for hyperpigmentation treatment. Glycolic extracts of Cecropia pachystachya Trécul are, therefore, the focus of this study. Its chemical characterization, antioxidant activity, tyrosinase inhibition, and cell viability were evaluated. Glycolic extracts were obtained by macerating the leaves of C. pachystachya in grain alcohol and glycerin or propylene glycol. Both had a similar chemical constitution, the glycerin being more efficient in concentrating phenolic compounds and flavonoids. Analyses by UHPLC-MS detected quinic acid, chlorogenic acid isomers, proanthocyanidin dimers type B and C, catechin/epicatechin, orientin/isoorientin, isoorientin 2”-O-xyloside, vitexin/isovitexin, and rutin. 5-O-caffeoylquinic acid was then quantified was then quantified, with predominance in the extract produced with propylene glycol. These extracts showed a high antioxidant capacity by the method of DPPH, β-carotene, and nitric oxide. As for depigmenting activity, both extracts were able to inhibit tyrosinase. Cell viability assay also revealed that the extracts could safely be used in concentrations of ≤ 125 µg/mL. Thus, this study demonstrated for the first time that the glycolic extracts of C. pachystachya have promising chemical and biological characteristics for the development of a multifunctional cosmetic with antioxidant and tyrosinase-inhibition activities.Resumo em Inglês:
Abstract The aim of the present study is to investigate the cardioprotective effects of 18β-glycyrrhetinic acid (18β -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18β-GA, and (4) 18β -GA+I/R. Ischemia was not applied to the sham and 18β-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18β-GA group, the mice were given 18β-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18β-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18β-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18β-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18β-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment.Resumo em Inglês:
Abstract The family Amaranthaceae contains a large number of halophytic species. The aim of this paper is to present a review of biologically significant halophytes in the flora of Serbia belonging to this family. This review includes a description of the following 18 species: Atriplex littoralis L., A. rosea L., A. halimus L., Bassia sedoides Pall., B. scoparia (L.) A.J.Scott., B. prostrata (L.) Beck., Beta trigyna W. et K., Camphorosma annua Pall., C. monspeliaca L., Chenopodium ambrosioides L., Ch. polyspermum L., Ch. vulvaria L., Ch. hybridum L., Ch. album L., Ch. rubrum L., Salicornia europaea L., Suaeda maritima (L.) Dum., Salsola soda L. These species are sources of biologically active substances and have a good potential for multi-purpose applications. Most extracts of these species have been found to exhibit biological activities such as antioxidant, anticancer, antibacterial, antifungal, antiinflammatory and others. The aim of this review is to describe these species including their morphology, distribution, phytochemistry, as well as their use for medicinal and food purposes.Resumo em Inglês:
Abstract The aim was to scrutinize the in vivo and in vitro activities against Leishmania tropica with compounds of Oxyresveratrol, Quercetin O-Hexoside, and Quercetin 3-Glucoside. The in vitro outcomes against Leishmania were analyzed for 24-48 hours on L. tropica KWH23 promastigotes with compounds materials having 50 - 200 µg/mL concentration with negative control and standard drug Amphotericin B. The compounds were analyzed in L. tropica infected BALB/c mice against Leishmania tropica. The Quercetin 3-Glucoside shows mean inhibition of extracellular promastigotes after 48 hours at 50, 100, 150, 200 µg/mL were 91.02 ± 0.12, 94.50 ± 0.07, 96.15 ± 0.17 and 97.01 ± 0.08 % respectively. In BALB/c mice, the intracellular amastigotes were 91% cured at 200 µg/mL and mean lesion size decreased to 0.41 ± 0.21 mm (p < 0.01). The result shows that Quercetin 3-Glucoside possesses significant anti-leishmanial activity.Resumo em Inglês:
Abstract In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.Resumo em Inglês:
Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4’-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.Resumo em Inglês:
Abstract Cashmirins A (1) and B (2), new prenylated coumarins, have been isolated from the EtOAc- soluble fraction of the whole plant of Sorbus cashmiriana Hedlung, Monog. along with seselin (3), scopoletin (4), 3-hydroxyxanthyletin (5) and luteolin (6), reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS, 1D and 2D NMR spectroscopy. Both new compounds 1 and 2 were investigated for biological activities and showed significant antifungal and urease inhibitory activities. Compounds 1 and 2 exhibited significant activity against Aspergillus flavus, Macrophomina phaseolina, Trichophyton simii, Trichophyton schoenleinii, and Pseudallescheria boydri. Both compounds also exhibited significant inhibitory activity against Jack bean urease with IC50 values of 28.2±0.12 µM and 30.3±0.18 µM, respectively compared to thiourea used as positive control.Resumo em Inglês:
Abstract Therapeutically, piracetam has been used for decades as a cognitive enhancer for memory- related neuronal disorders. The present study aimed to investigate the neuroprotective potential of piracetam on lipopolysaccharides (LPS)-induced neuronal deficit using both in-vitro and in-vivo experimental models. For the in-vitro analysis, EOC-20 murine microglial cells were induced with a neuronal toxicity of 100 µg/ml of LPS, and the formation of intracellular reactive oxygen species (ROS) and nitric oxide (NO) productions were determined. For in-vivo neuroprotective analysis, groups of mice were treated orally with two doses of piracetam (200 and 400 mg/kg) for 30 days. Neuronal toxicity was induced by four intraperitoneal injections of LPS (250 µg/kg/day). The malondialdehyde (MDA) level was measured for oxidative stress, and catalase reduced glutathione (GSH), glutathione reductase (GRD), and superoxide dismutase (SOD) levels were determined as the antioxidant parameters. The result of the cell viability study was that pre-treatment with piracetam significantly protected the LPS-induced cell loss, and attenuated the ROS generation and NO production in LPS-induced EOC-20 cells. Moreover, the treatment of piracetam significantly reduced the MDA levels and improved catalase, GSH, GRD, and SOD activities in LPS-induced mice brains. The overall results from this study supported the neuroprotective effects of piracetam against LPS-induced neuronal toxicity.Resumo em Inglês:
Abstract Evaluation of montmorillonite for paraquat by in vitro and in vivo test. In vitro test were evaluated by a batch test, taking the paraquat concentration, adsorbents, reaction environment and time as indices, the absorption rate was screened by orthogonal design. In vivo test was executed with rabbits. Group 1: 4 rabbits dosed with montmorillonite. Group 2: 8 rabbits dosed with 200 mg/kg paraquat. Group 3: 6 rabbits dosed with 200 mg/kg paraquat then gavage with montmorillonite 5 min later. Group 4: 6 rabbits dosed with 200 mg/kg paraquat then gavage with montmorillonite 30 min later. Blood paraquat concentration, serum cytokines, blood gas analysis and histopathology of lung were implemented. In vitro test found that all the four factors influence the absorption rate of paraquat (P < 0.05). In vitro test found that oral montmorillonite could change toxicokinetics parameters of paraquat (P < 0.05); decrease raised serum TGF-β1 and HMGB1 (P < 0.05) and alleviate the histopathology damage of lung. Montmorillonite might exert its protective effects on paraquat induced damage.Resumo em Inglês:
Abstract The potential of the biome caatinga (exclusive from northeastern Brazil) has been evaluated in recent research for application in the pharmaceutical industry. Among the species of medicinal plants from caatinga, one can highlight the Commiphora leptophloeos (umburana), which has been used as infusions and syrups by the regional population for inflammatory and infectious diseases. Essential oils from umburana leaves and barks were obtained in a Clevenger apparatus and analyzed by gas chromatography/mass spectrometry, and total phenolic and flavonoids were determined by spectrophotometric analysis. It was observed that a large part of the major compounds present in the essential oil is described as having antitumor activity, enabling research in investigational oncology with umburana (C. leptophloeos). In addition, some little explored components have been identified, such as cadinene, alpha-selinene, and elemenone. Despite being easily found in several plants, there are no clinical trials involving their biological activity in a well-defined isolated form, which could make exploring new studies possible. Furthermore, the presence of phenolic compounds and flavonoids allows future studies about the potential antimicrobial and antioxidant activity.Resumo em Inglês:
Abstract The effects of Rheum ribes on lead acetate levels and hepatic biochemical factors due to lead acetate toxicity were investigated. Forty male Wistar rats were designated into four groups: Control; lead acetate (receiving in drinking water at 0.6 g/L, daily); hydroalcoholic extract groups (200 and 400 mg/kg doses, gavage, once daily). Treatments were conducted for 10 days. On the 11th day, blood samples were collected to measure lead acetate levels and biochemical factors. Liver tissue samples were examined for histopathological changes. Lead serum levels were increased in lead acetate-treated rats (p<0.001). Lead acetate treatment was associated with a significant increase in liver tissue damage (p<0.001), while R. ribes extract prevented liver tissue damage (p<0.05). The levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the groups lead acetate + extract (two doses) than in the lead acetate group (p<0.001 and P<0.01, respectively), but alkaline phosphatase level, prothrombin time, partial thromboplastin time and international normalized ratio were not different between the lead acetate + extract groups and the lead acetate group. The results showed the inhibitory role of R. ribes on lead-induced hepato-toxicity. The results make Rhubarb a good candidate to protect against the deleterious effect of chronic lead intoxication after complementary studies.Resumo em Inglês:
Abstract In this paper, the chemical constituents, larvicidal and antimicrobial activities of hydrodistilled essential oils from Zingiber castaneum Škorničk. & Q.B. Nguyễn and Zingiber nitens M.F. Newman were reported. The main constituents of Z. castaneum leaf were bicyclogermacrene (24.8%), germacrene D (12.9%), cis-β-elemene (11.2%) and β-pinene (10.3%), while sabinene (22.9%) and camphene (21.2%) were the significant compounds in the rhizome. However, the dominant compounds in the leaf of Z. nitens includes β-pinene (45.8%) and α-pinene (10.7%). Terpinen-4-ol (77.9%) was the most abundant compound of the rhizome. Z. castaneum rhizome oil displayed larvicidal activity against Aedes aegypti and Culex quinquefasciatus with LC50 values of 121.43 and 88.86 µg/mL, respectively, at 24 h. The leaf oil exhibited activity with LC50 values of 39.30 µg/mL and 84.97 µg/mL, respectively. Also, the leaf and rhizome oils of Z. nitens displayed greater larvicidal action towards Ae. aegypti with LC50 values of 17.58 µg/mL and 29.60 µg/mL, respectively. Only the rhizome oil displayed toxicity against Cx. quinquefasciatus with LC50 value of 64.18 µg/mL. All the studied essential oils inhibited the growth of Pseudomonas aeruginosa ATCC25923 with minimum inhibitory concentration (MIC) value of 50.0 µg/mL. This paper provides information on the larvicidal and antimicrobial potentials of Z. castaneum and Z. nitens essential oils.Resumo em Inglês:
Abstract This study aimed to develop a simple and fast capillary electrophoresis (CE) method for the simultaneous determination of adenosine triphosphate (ATP) and its metabolites in dietary energy supplements. Reverse polarity separation mode for faster separation of the three strong negatively charged analytes and capillaries with a 25 µm inner diameter was employed. At -433 V/cm field strength at background electrolyte (BGE) consist with 0.1 M tris-HCl, 0.5 mM tetradecyltrimethylammonium chloride (TTAC) as positively charged surfactant and 0.3 mg/mL hydroxypropylmethylcellulose (HPMC) to reduce the electroosmotic flow (EOF), a complete separation of the three species were achieved in less than 15 minutes. The data acquisition was conducted at a wavelength of 254 nm. Three different commercialised dietary energy supplements were analysed.Resumo em Inglês:
Abstract The histological structure and biochemistry of the skin is affected by solar radiation having adverse effects ranging from sunburns, premature aging that includes wrinkles, spots, dryness, and loss of collagen to cancer development. The skin has defense mechanisms to prevent damage caused by radiation, but when radiation exposure is excessive these mechanisms are not strong enough to protect the skin. The use of sunscreen is the most common practice of photo- protection. The active ingredients of these cosmetic protective formulations are generally from synthetic origin and have presented several drawbacks at the level of photo-stability, systemic absorption and can generate contact and photo-contact dermatitis. This review illustrates skin solar radiation problems, common sunscreen ingredients limitation and mentions how algae can be an alternative according to studies that have evaluated the photo-protective potential of extracts and compounds isolated by different techniques.Resumo em Inglês:
Abstract Pregabalin, a GABA analogue is used to treat epilepsy and neuropathic pain. The drug poses problems in analytical quantification when estimated at a shorter UV wavelength. The expensive and non-repetitive reported analytical methods necessitate the utility and development of an accurate, precise, repetitive, simple and highly sensitive colorimetric method for pregabalin in solution as well as sustained release mini matrices. Pregabalin (having primary amino group) was derivatized at alkaline pH of mixture with optimized ninhydrin solution at ambient temperature (25oC). The ninhydrin-pregabalin derivatized complex (Ruhemann’s Purple) was analyzed for drug concentration at absorption maximum (λmax) of 570nm. The linearity was observed in the concentration range of 5-150 µg/mL with coefficient of correlation, 0.998. The developed analytical method was validated according to ICH guidelines and proved to be highly sensitive (LOD 0.917µg/mL, LOQ 3.055µg/mL), with good inter-day as well as intra-day accuracy and precision as 4.65% and 3.75%, respectively. The proposed method was proved to be a simple, sensitive, precise and accurate for the estimation of the minute concentrations of pregabalin in pure form and the developed formulations. Results verified that the proposed method could determine pregabalin at the ambient temperature without requiring high temperatures used in the existing methods. It was concluded that developed method was easier and more suitable for analysis of pregabalin in quality control of commercial preparations.Resumo em Inglês:
Abstract Fridericia caudigera and Cuspidaria convoluta (Bignoniaceae) species, which grow in the northwest of Argentina, have shown antibacterial effect against strains isolated from skin infections, and each one displayed synergism with commercial antibiotics. The aims of this work were to evaluate the antibacterial activity and toxicity of the combination of these two plant species, and to design a stable gel for topical use including the blend of extracts. The combination of extracts was evaluated for synergistic effects (chequerboard assay), genotoxicity (Ames test) and cytotoxicity (Artemia salina test). A gel was subsequently formulated with the combination of extracts using carboxymethylcellulose as a polymer. The following physico- chemical characteristics of the gel formulation: pH, viscosity, spreadability and total phenol content, as well as resistance to severe temperature changes, biological activity (diffusion in agar), in vitro permeation (Franz cells) and primary dermal irritation (Draize test) were analyzed. The combination of extracts showed a synergistic effect on pathogenic bacteria and was not toxic in the in vitro tests. The gel was stable and retained the antimicrobial activity of the original extracts. The formulation proposed in this work could constitute an alternative for primary skin infections since it proved to be safe for topical administration.Resumo em Inglês:
Abstract Cerebrovascular disease is the second most serious disease in the world. It has the features of high morbidity, high mortality and recurrence rate. Numerous research on the compatibility of Chinese medicine with effective ingredients of cerebral ischemia has been made during the past decades. The purpose of this study is to quantitatively analyze the combined pharmacological effect of effective ingredients in Danshen and Honghua (Dan Hong) on rat microvascular endothelial cells after gradually oxygen-glucose deprivation. The experimental concentration range for the compatibility of two effective ingredients were determined in the preliminary experiments by Cell Counting kit-8 (CCK-8) method. Drugs were added to rat brain microvascular endothelial cells at a non-toxic dose level. After that, the cells were cultured for 12 h, and placed in a hypoxic environment. Finally, the cell survival rate was used as a measure of drug effect. In order to determine synergism or antagonism, the combination index (CI)-isobologram method was performed to analyze the data from the experiments. Based on this theory, the potencies of each drug and the shapes of their does-effect curves are both taken into account. The results show that the synergism or the antagonism between two effective ingredients compatibility change with different proportion and dosage. Furthermore, it can be seen from the results of these experiments that when these drugs are used in combination, the dosage required to achieve the same therapeutic effects is greatly reduced compared with the case of single one. It is worth mentioning that our experiments also prove that the median-effect equation and the CI method can be applied in the field of traditional Chinese medicine.Resumo em Inglês:
Abstract As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have been attracting increasing attention in recent years. Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure, and possesses many biological activities. However, its clinical application is significantly limited mainly due to its low oral bioavailability caused by poor hydrophilicity. To address this, ISL nanocrystals were developed in this study to improve its oral bioavailability. Three types of nanocrystals with differing particle size; R1, R2, and R3, were prepared by anti- solvent precipitation or anti-solvent precipitation combined with sonication, which was optimized by single-factor experiments. These nanocrystals were characterized based on their physical properties, in vitro release, and in vivo absorption performance. The mean particle size of R1, R2, and R3 was 555.7, 271.0, and 46.2, respectively. The dissolution ratio of ISL in the nanocrystals was significantly improved, with the quickest rate recorded in R2. Peak concentration and area under the concentration-time curve of R2 after oral administration in rats was 5.83- and 2.72-fold higher than that of the ISL solution, respectively. These findings indicate that the dissolution and absorption of ISL can be significantly enhanced by nanocrystals, and the dissolution behavior and pharmacokinetic properties of nanocrystals is significantly influenced by particle size.Resumo em Inglês:
Abstract Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short- or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.Resumo em Inglês:
Abstract This study aimed to evaluate the incidence of medication errors over a period of one year in King Fahad Hospital Madina Saudi Arabia. This retrospective, cross-sectional study was conducted over a period of one year from 2018 January to 2018 December using patient’s records. King Fahad Hospital in Madina was selected for the study center. Data collected include the number and types of errors, severity, location of errors, errors by profession, and errors occurred in the medical wards. Statistical analysis was carried out using statistical package for social science version22. A total of twenty- six hundred and fifty-eight medication errors were reported during the study period. Among the reports 2567(96.5%) of the errors were due to near misses, followed by transcribing errors 1597(60%), ordering errors 928(34.9%), duplicative therapy 765(28.7%), wrong dose 454(%). The most common procedures involve medication errors were wrong documentation 442(16.6%), duration 168(6.3%) wrong quantity 162(6.4%). Majority of the medication errors were contributed by physicians (99.2%) and 0.7% of them were due to the pharmacist. In conclusion study findings reported that yet some kind of medication errors has been under reported and it was common in most hospital, further studies with intervention programs needed to control the incidence of medication errors in a Saudi hospital.Resumo em Inglês:
Abstract The present study describes chemical composition, phytochemicals, antifungal activities, antioxidant assays and total phenolic content of essential oil and varied polarity solvent extract from flowers of Alpinia malaccensis (Burm.f.). Total 27 components were identified in essential oil by GC-MS with terpinen-4-ol (28.6%) and α- terpineol (12.8%) as the main constituent. The essential oil was found to have maximal levels of phenolic content (64.60 μg/mL) as compared to the other extracts. The antioxidant assay evaluated in extracts and essential oil by different methods revealed good-to-moderate antioxidant potential with different IC50 values viz. (188.02 -250.25 μg/mL) in Fe3+ reducing power, (153.15-201.59 μg/mL) in Fe2+ metal-chelating ability, (130.39-181.12 μg/mL) in DPPH, (88.29-187.32 μg/mL) in OH radical, (79.04-156.79 μg/mL), in NO radical and (138.72-233.00 μg/mL) in superoxide anion scavenging activities, respectively. The methanolic extract display remarkable fungicidal activity against the tested pathogens followed by dichloromethane extract, essential oil, hexane extract and petroleum ether extract respectively, with MIC values ranging from 31.25 to 500 μg/mL. Based on results, it can be inferred that the flower of A. malaccensis if explored further for its medicinal properties, might be a good source to develop a safe and sustainable natural food preservative.Resumo em Inglês:
Abstract Fenofibrate is a peroxisome-proliferator-activator α agonist and it is a widely used drug for hyperlipidemia since its approval in 2004. So, in this review we are focusing on the effect of fenofibric acid’s mechanism to alleviate type 1 diabetic micro vascular complications like diabetic retinopathy, diabetic cardiomyopathy in animal models, since the drug is safe, efficacious and more economical when compared with the currently available treatment strategies for juvenile diabetic complications and also a profound observation is needed due to the rarity of research in these therapeutic areas. Important preclinical animal studies published from January 2001 to June 2020 were recognised from databases like PubMed and Cochrane central register of controlled trials. Reviewers screened the articles based on the selection criteria and risk of bias was determined using Systematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies. Our literature search yielded a total of 5 studies and after pooling up the data from the 5 preclinical studies, we found that Fenofibrate have the efficacy to prevent type 1 diabetic complications, chiefly diabetic retinopathy and those mechanisms are dependent on peroxisome-proliferator-activator and fibroblast growth factor-21 pathways. Fenofibrate is a well safe and moreover, cost effective medication in preventing type 1 diabetic micro vascular complications especially diabetic retinopathy and also in maintaining the glucose homeostasis in apart from its anti-dyslipidemic effect.Resumo em Inglês:
Abstract The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice.Resumo em Inglês:
Abstract Development and validation of a simple and fast method of high-performance liquid chromatography with diode array detection (HPLC-DAD) for the simultaneously analysis of rutin, avobenzone, and octyl p-methoxycinnamate is presented. These substances were separated using a Kromasil C18 (250×4.6 mm, 5 μm) column, methanol: water (88:12 v/v) as the mobile phase, and a flow rate of 0.8 mL min−1. The experiment was performed at room temperature and elution was under isocratic conditions. Quantification was performed by external calibration at the wavelength of 325 nm. The validated parameters included linearity, selectivity, precision (repeatability), intermediate precision, accuracy, limit of detection, limit of quantification and robustness. The results of validation were statistically treated using the Action Stat version 3.5.152.34. The selectivity was also evaluated in the presence of two cyclodextrins (2-hydroxypropyl-β-cyclodextrin and β-cyclodextrin sulfobutyl ether sodium). The absence of parallelism between the curves of octyl p-methoxycinnamate in the absence and presence of the β-cyclodextrin sulfobutyl ether sodium in the mobile phase revealed interference from this matrix, thereby indicating the necessity of validating the method in the presence of this, and other matrices. The proposed method was selective, linear, precise, accurate, and robust for the simultaneous determination of rutin, avobenzone, and octyl p-methoxycinnamate.Resumo em Inglês:
Abstract Malaria is a disease caused by Plasmodium spp. protozoa. The ability of Plasmodium to develop resistance to current antimalarial drugs makes the study of chemotherapeutic alternatives extremely important. This study aimed to evaluate the antimalarial activity of compound 3286938 (1-(3-benzyloxy-4-methoxy-phenyl)-3-(3,4,5-trimethoxy-phenyl)-propan-1-one), which presents in its structure a 3,4,5-trimethoxyphenyl group, in vitro, using the W2 strain of P. falciparum and against circulating strains of P. vivax and P. falciparum from the state of Rondônia. The compound 3286938 obtained an IC50 of 24.4 µM against the W2 strain of P. falciparum, and against the circulating strains, it presented a median (MD)=38.7 µM for P. vivax and MD=6.7 µM for P. falciparum. As for toxicity, 3286938 showed CC50 > 500 µM for VERO and HepG2 strains with a selectivity index greater than 12.9, a ratio calculated for P. falciparum and P. vivax regarding Vero and HepG2 cells. The compound was not considered hemolytic in in vitro assays, thus indicating the specificity of its antiplasmodial action. Based on the results presented, and considering the unprecedented character of the compound, it can be concluded that 3286938 was shown to be promising for complementary in vitro and in vivo studies aiming to produce effective antiplasmodial action.Resumo em Inglês:
Abstract Sunset yellow (SY), allura red (AR) and fast green (FG) are frequently used in commercial food products, although they are considered to be hazardous to public health due to their toxic efficacy and high exposure risk potency. In this study, a new, rapid, and reliable method based on a magnetic solid-phase extraction (MSPE) was developed for the simultaneous determination of SY, AR, and FG. Fe3O4 modified with Elaeagnus angustifolia was used for the first time as an adsorbent (Fe3O4-EA) in MSPE. It was characterized with scanning electron microscopy, Brunauer Emmet Teller surface area analysis and X-ray diffraction. MSPE parameters were optimized in terms of pH, adsorption, and elution time and elution volume. High-performance liquid chromatography was used for dye quantitation. Analytical separation was performed by applying ammonium acetate buffer, acetonitrile, and methanol as the mobile phase to a C18 reverse-phase analytical column. Intraday and inter-day repeatability of the method performed at the concentration of 0.2, 1.0 and 2.0 µg/mL exhibited <8.1% RSD (n=3). The limit of detection values was between 0.05-0.1 µg/mL. The adsorption data of SY, AR and FG on Fe3O4-EA were fitted with the Langmuir model with qmax values of 45.0, 70.4 and 73.0 mg/g, respectively.Resumo em Inglês:
Abstract Plants from genus Ephedra are commonly used by the Chinese people as folk medicine for treatment of various diseases. The current study was designed to explore the ethno-pharmacological based pharmacological potentials of Ephedra intermedia Schrenk & C.A. Mey. (E. intermedia). Plant aerial parts were extracted using ten solvent systems with increasing order of polarity. Samples were analyzed for total phenolic and flavonoid contents, HPLC-DAD analysis, antibacterial, antifungal, HepG2 cell line cytotoxicity, hemolysis and antioxidant potentials following standard procedures. Highest percent extract recovery was observed in Eth+WT (25.55 % w/w) solvent system. Flavonoid and phenolic contents were higher in chloroform and Met+WT fractions respectively. Considerable antibacterial activity was shown by Eth+Met extract against B. subtilis and K. pneumonia (MIC of 11.1μg/mL for each). Eth extract exhibited high antifungal activity against A. fumigates (15±0.31 mm DIZ). Met+WT extract showed significant cytotoxicity against HepG2 cell lines with IC50 of 13.51+0.69 μg/mL. Substantial free radical scavenging activity (74.9%) was observed for Met+Eth extract. In the current study, several solvent systems were used for more effective extraction of fractions and can be useful in the isolation of phytochemicals. Various fractions exhibited considerable antimicrobial, antioxidant and cytotoxic potentials. Biological potentials of E. intermedia signify its potential uses in microbial, cancer and degenerative disorders and thus warrant further detailed studies.Resumo em Inglês:
Abstract Huge plethora of studies pointed out the importance of several Artemisia herb molecules as treatment for many diseases. Among these natural substances, some molecules are known to counteract fever, inflammation, blood clotting and oxidative stress. Furthermore, they are dotted with activities against different strains of viruses including the SARS-coronaviruses. For these beneficial properties, these medicinal herbs are deemed as a potential candidate for covid-19 pandemic.Resumo em Inglês:
Abstract The objective of this study was to assess how different modes of steroid therapy affect hearing preservation in Partial Deafness Treatment group of patients. In this study, the group consisted of 46 (24 women, 22 men; aged 18-78 years) cochlear implant patients divided into 3 subgroups. In the first subgroup (N = 13), patients underwent standard intravenous (IV) steroid therapy following implantation. In the second (N = 16), patients underwent prolonged treatment with a combination of oral and IV corticosteroids. Third subgroup (N = 17) was a control group who received no steroids therapy. The mean hearing preservation rate was 52.1% (SD = 36.7) in patients receiving standard steroid therapy, 71.4% (SD = 22.7) in patients with prolonged steroid therapy, and 22.1% (SD = 33.9) in control patients. The smallest variation of hearing preservation rate was observed in patients with prolonged steroid therapy and was 9.9 dB. In comparison, the mean change in patients with standard steroid therapy was 11.7 dB and for control patients the figure was 18.0 dB. A combination of intravenous and oral steroid therapy seems to be optimal and stabilizes hearing thresholds and preserves hearing.Resumo em Inglês:
Abstract Damage resulting from the incidence of ultraviolet (UV) radiation on the skin is common nowadays, with UVB (290-320 nm) and UVA (320-400 nm) radiation responsible for photoaging, sunburn and carcinogenesis. For this reason, sunscreens represent products of growing interest to prevent such damage. However, there are few organic filters marketed worldwide with photostability and effectiveness at wavelengths greater than 340 nm (long UVA), which justifies the exploration for new compounds. In this work, we determined the photostability and sun protection factor (SPF) of three 2-(2’-hydroxyphenyl)benzoxazole derivative dyes in order to develop new organic UV filters. UV-vis spectrophotometry has high level of reproducibility when compared with in vivo human clinical methods. Solubility determinations were performed in different solvents. The compounds absorbed UVA and UVB radiation, with maximum absorption wavelengths ranging from 336 to 374 nm. Photostability was evaluated using a solar simulator (3 J.m2.s-1 UVA radiation) for a maximum of 3 h. The 2-(amino-2’-hydroxyphenyl) benzoxazoles showed higher photostability than the acetylated derivative under the evaluated conditions. The three benzoxazoles presented SPF values of around 40 and preliminary results indicate that they show suitable properties to act as good chemical filters in photoprotective formulations.Resumo em Inglês:
Abstract Polyelectrolyte complexes (PECs) as drug delivery systems are widely explored since they are easily obtained by coacervation and biopolymers can be associated. However, particle distribution is a challenging critical parameter that has been infrequently focused. This work evaluated the effect of NaCl concentration on the physicochemical properties of PECs based on chitosan and hypromellose loaded with methotrexate. The particle size, zeta potential and polydispersity index (PdI) were determined by DLS, besides of drug entrapment efficiency (EE) and in vitro drug release profile determination. Particle size decreased while NaCl concentration rised, achieving a narrower size distribution of (345±79 nm) and PdI (0.285±0.067) with 200 mmol/L NaCl. The higher the NaCl concentration, the lower the zeta potential at acid pH. The EE was kept similar ((28.2±4.5) %) from 0 to 300 mmol/L NaCl, while 400 mmol/L NaCl impaired the drug entrapment. The addition of (200 and 300) mmol/L NaCl did not affect the drug release profile, but it was faster with (100 or 400) mmol/L. In conclusion, the addition of 200 mmol/L NaCl reduced particle size and PdI with no changes in the EE and drug release. Therefore, the ionic strength plays an important role on PECs development.Resumo em Inglês:
Abstract The objective of the present study is to develop and validate a simple, selective and accurate hydrophilic interaction liquid chromatography - a high performance liquid chromatography incorporating an evaporative light scattering detector (HILIC-HPLC-ELSD) method for simultaneously determining glucosamine hydrochloride and chondroitin sulfate in dietary supplements. The chromatographic separation was carried out on a ZIC-HILIC column (150 mm x 4.6 mm x 5µm) in isocratic system mode with a mobile phase of acetonitrile, 30 mM ammonium formate and water (77:20:3, v/v/v) at pH 4.5, a column temperature of 35°C, a flow rate of 1 mL.min-1, and an injection volume of 5 µL. An evaporative light scattering (ELS) detector was used. Effective separation was achieved by means of analyte resolution of more than 1.5 with an analysis run time of approximately 20 minutes. The linearity of glucosamine hydrochloride and chondroitin sulfate ranged from 0.4 to 2.5 mg.mL-1. The limits of the detection and quantification of glucosamine hydrochloride were 20 and 80 mg.mL-1 respectively, while for chondroitin sulfate they were 80 and 400 mg.mL-1. All validation parameters satisfied the acceptance criteria in accordance with International Conference on Harmonisation (ICH) guidelines. The method was successfully applied to the assay of commercial dietary supplement samples.Resumo em Inglês:
Abstract This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications.Resumo em Inglês:
Abstract The present study has been carried out with the seed extracts of Nyctanthes arbor-tristis L. (Parijat) and evaluates its antioxidant potential and profiling the phytochemical constituents by Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The antioxidant potential of the seed extracts was measured by four different in vitro assay like 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, superoxide anion free radical scavenging activity, ferric reducing antioxidant power (FRAP) and lipid peroxidation inhibition potential (LPIP) assay. The total phenol content (TPC) and total flavonoid content (TFC) were estimated. The ethyl acetate extract (EAE) of seeds showed potential DPPH free radical scavenging activity (EC50 129.49±3.55µg/ml), superoxide anion radical (EC50 969.94±8.03µg/ml) and LPIP (EC50 452.43±5.07 µg/ml) activities. The total phenol content was maximum in aqueous extract (AQE) which was 201.00±0.20 µg/mg gallic acid equivalent. The EAE was rich with total flavonoid and it was found to be 34.50±0.40 µg/mg rutin equivalent. The EAE was subjected for phytochemical-profiling using GC-MS system. The presence of different phytoconstituents supports the medicinal value of the seeds. The results suggest that EAE constitutes a promising new source of novel compounds. Further, it can be used for isolation and purification of specific compounds which have good antioxidant activities and possess useful biological activities.Resumo em Inglês:
Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future.Resumo em Inglês:
Abstract Quality of groundwater is threatened due to pollution by industrial, domestic and agricultural waste. A large number of populations are residing in rural areas which are unable to afford high cost water purifiers due to their low income as well as limited awareness. However, limited availability of fresh water has become a critical issue in developing countries. Around 1.2 billion population is deprived of affordable and safe water for their domestic need. Additionally, chemical coagulants which are nowadays being used for water purification pose severe and numerous health hazards to human. Thus utilization of easily accessible natural coagulant for water purification might offer a sustainable, practical and cost effective solution to the current alarming situation in developing countries. Several experimental findings have shown strong efficiency of Moringa oleifera plant extracts obtained from different solvents in the improvement of water quality parameters including physicochemical (such as pH, hardness, turbidity, metallic impurities, total dissolved solid) and biological (E.coli count) parameter. We have also highlighted the limitations and advantages of chemical coagulation in water purification. Altogether, this review summarizes one such miracle tree which has shown significant potential as a natural coagulant and its associated underlying mechanism in water purification process.Resumo em Inglês:
Abstract Degenerative diseases diabetes and oxidative stress constitute a major health concern worldwide. Medicinal plants are expected to provide effective and affordable remedies. The present research explored antidiabetic and antioxidant potential of extracts of Carissa opaca roots. Methanolic extract (ME) was prepared through maceration. Its fractions were obtained, sequentially, in hexane, chloroform, ethyl acetate and n-butanol. An aqueous decoction (AD) of the finely ground roots was obtained by boiling in distilled water. The leftover biomass with methanol was boiled in water to obtain biomass aqueous decoction (BAD). The extracts and fractions showed considerable porcine pancreatic α-amylase inhibitory activity with IC50 in the range of 5.38-7.12 mg/mL while acarbose had 0.31 mg/mL. The iron chelating activity in terms of EC50 was 0.2939, 0.3429, 0.1876, and 0.1099 mg/mL for AD, BAD, ME, and EDTA, respectively. The EC50 of beta-carotene bleaching activity for AD, BAD, ME, and standard BHA were 4.10, 4.71, 3.48, and 2.79 mg/mL, respectively. The total phenolic content (TPC) and total flavonoid content (TFC) of AD and BAD were also considerable. In general, ethyl acetate fraction proved to be the most potent. Thus, the C. opaca roots had excellent antioxidant activity while having moderate α-amylase inhibitory potential.Resumo em Inglês:
Abstract The therapeutic drugs to treat Herpes simplex virus (HSV) infections have toxic side effects and there has been an emergence of drug-resistant strains. Therefore, the search for new treatments for HSV infections is mounting. In the present study, semi-solid formulations containing a crude hydroethanolic extract (CHE) from Schinus terebinthifolia were developed. Skin irritation, cutaneous permeation, and in vivo therapeutic efficacy of the formulations were investigated. Treatment with the ointment formulations did not result in any signs of skin irritation while the emulsions increased the thickness of the epidermis in Swiss mice. The cutaneous permeation test indicated that the CHE incorporated in the formulations permeated through the skin layers and was present in the epidermis and dermis even 3 h after topical application. In vivo antiviral activity in BALB/c mice treated with the CHE ointments was better than those treated with the CHE emulsions and did not significantly differ from an acyclovir-treated group. Taken together, this suggests that the incorporation of CHE in the ointment may be a potential candidate for the alternative topical treatment of herpetic lesions.Resumo em Inglês:
Abstract Pharmaceutical education should enable the development of competences for community pharmacy practice, which is an important field for the pharmacist workforce. The aim of this study was to evaluate the competences perceived by pharmacy interns from a Brazilian pharmacy school for community pharmacy practice. This study adopted a combined quantitative and qualitative approach. The study cohort included undergraduate students who undertook internships in community pharmacy in the final year of the pharmacy course. Students responded to an 11-item structured questionnaire according to a five-point Likert scale that included perceptions of their competences for community pharmacy practice. Among the 693 possible answers, 605 (87.3%) agreed that the course promoted the development of competences for professional practice in community pharmacy. Less than 70% of students perceived themselves as prepared to respond to symptoms and provide non-prescription medicines. Qualitative analysis of the comments revealed three themes: the need to improve patient information skills, improve practice as a member of a health care team, and improve dispensing according to legal requirements. These findings may support improvements in undergraduate pharmacy programs, such as the inclusion of experiential learning, active learning methods, interprofessional education, and development of clinical skills.Resumo em Inglês:
Abstract We were carried out to investigate the efficacy of Rape (Rapeseed, Brassica napus L.) flower on BPH (benign prostatic hyperplasia) in rats. We found that the extract from Rape flower prevented hyperplasia in testosterone-induced BPH model, the relevant animal model of human BPH. Extract reduced the weight of prostate and induced significantly cell apoptosis in prostate in BPH model. In addition, the extract controlled expression of TGF-β1 in prostate gland and promoted urinary output in dose-dependence in BPH model. Our data provide that Rape flower may be useful for treatment of BPH.Resumo em Inglês:
Abstract The reasons for the recently observed increase in the incidence of breast cancer in the Indian population are not clearly understood, but thought to be largely explained by westernization of lifestyles and changes in reproductive behavior, which characterize exposure to hormones. Our aim is to review the reproductive risk factors and comorbidities and evaluate the association between molecular subtypes of breast cancer. A hospital-based analytical case-control study was conducted among the breast cancer cases with controls in a multispecialty teaching hospital for a period of one year. Totally, 130 subjects were recruited and an interview was conducted using a structured questionnaire to obtain demographic and risk factor data, including tissue marker status (ER, PR and HER-2) obtained from case files. Data were analyzed with SPSS-20 version. Results: The highest age group reported in this study was 51- 60 years which has a 3.8 times increased risk compared to other age and the age group of 31- 40 have a decrease risk of 0.33. In this study, the percentage of post menopause (68%) and mothers not breastfeeding (10%) was higher in cases compared to controls and a noted increase in the risk of breast cancer with odds ratio (OR) of 2.745 (p= <0.0001) and 9.08 (p=0.01) respectively. Duration of breastfeeding showed significantly (p=<0.0001)) moderate positive correlation (r=0.549, 0.457, 0.418 and 0.636) for luminal A, luminal B, HER+, and triple negative respectively. This study found that all the reproductive risk factors do not have correlation with a molecular subtype of breast cancer except breastfeeding. Post menopause and breastfeeding were common factors associated with all people and could be modifiable to prevent the occurrence of breast cancer through lifestyle changes.Resumo em Inglês:
Abstract On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.Resumo em Inglês:
Abstract The use of plants in disease treatment is cost effective and relatively safe. This study was designed to investigate anti-hyperlipidemic and anti-diabetic activity of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy in hyperlipidemic & diabetic mice. Eight groups comprising five mice each were used. Group A was hyperlipidemic control, group B, C, D received atorvastatin (20 mg/kg), leaf extract (200 mg/kg) and leaf extract in combination with atorvastatin (200 mg/kg and 20 mg/kg) orally for 15 days. Group E was diabetic control. Group F, G, H received sitagliptin (40 mg/kg), leaf extract (200 mg/kg) and extract in combination with sitagliptin (200 mg/kg and 40 mg/kg) orally for 7 days. Blood cholesterol levels were measured at 1st, 5th, 10th and 15th day and fasting blood sugar levels were measured at 2, 12, 24, 72 and 168 hours during treatment. One-way ANOVA with tukey- kramer multiple comparison test was used. The chemical characterization of ethanolic extract of Catharanthus roseus leaves showed presence of alkaloids, saponins, tannins and flavonoids. Ethanolic extract of Catharanthus roseus has significant anti-hyperlipidemic & anti-diabetic effects (p<0.05, p<0.01) when compared with control but had not cause significantly increase in anti-hyperlipidemic effects of atorvastatin. While significantly increased the antidiabetic effect of sitagliptin (p<0.05).Resumo em Inglês:
Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.Resumo em Inglês:
Abstract To assess the performance indicators for pharmaceutical services (PS) in primary health care (PHC), the level of satisfaction with pharmacy services among users and managers / pharmacists’ impressions in relation to the findings were evaluated. The study used mixed methods, including a retrospective and descriptive study of the performance indicators for PS in PHC, an observational study on the level of satisfaction and a qualitative study of users’ perception of pharmacy services at Health Units. Managers and pharmacists’ impressions of the study results were also collected. Only 44.4% of pharmacies had a full-time pharmacist. From the establishments visited, 5.3% did not have an air-conditioned environment, and only 33.3% of the items essential to the Good Practices of Storage of Medicines and Supplies criteria were fulfilled. Although 77.9% of the prescribed medicines were dispensed, it did not reach the 80% standard. The satisfaction level of users was 3.2±0.6, indicating dissatisfaction with pharmacies’ services. By means of an evaluation of each item within the questionnaire, it was possible to observe that variables related to pharmaceutical care presented low scores in relation to other domains, thus evidencing the fragility of the pharmaceutical- patient relationship in users’ perception. Managers and pharmacists suggested that these results were related to the inadequate physical infrastructure of pharmacies, work overload, lack of recognition and undervaluation of pharmacists, lack of interaction within the PHC team, high turnover of pharmacists, and lack of PS prioritization by the administration. PS in PHC has structural and organizational weaknesses that require changes. In general, users are dissatisfied with pharmacies’ services, especially with pharmaceutical care.Resumo em Inglês:
Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.Resumo em Inglês:
Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.Resumo em Inglês:
Abstract Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.Resumo em Inglês:
Abstract The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.Resumo em Inglês:
Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.Resumo em Inglês:
Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.Resumo em Inglês:
Abstract The aim of this study was to determine antimicrobial activities of Alchemilla mollis, Alchemilla persica as well as ellagic acid and miquelianin against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans by using microbroth dilution method and anti-inflammatory activity by using human red blood cell (HRBC) membrane stabilization method. Microbroth dilution method was used to determine the antimicrobial activities. Extracts possessed activity having MIC values of 2.5-5-10mg/ mL, compounds possessed activity having MIC values of 1.25-2.5-4-5mg/mL. A.mollis aerial parts displayed the highest anti-inflammatory activity (IC50=1.22±0.07mg/mL). Ellagic acid and miquelianin were also determined as anti-inflammatory agents with 0.57±0.01mg/mL and 1.23±0.02mg/mL IC50 values, respectively. Total phenolic content and tannin content of the A.mollis and A.persica were determined as 357.00±75.80mg, 282.50±28.70mg PGE/g plant material and 18.02%, 18.63% respectively according to the method described by European Pharmacopoeia. Ellagic acid, miquelianin and catechin were analyzed by HPLC. The highest catechin content was detected in A.persica roots (6.69±0.05g/100g plant material). A.mollis aerial parts contain higher miquelianin (0.39±0.02g/plant material) and ellagic acid (1.56±0.01g/ plant material) than A.persica.Resumo em Inglês:
Abstract Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-β-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-β-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali.Resumo em Inglês:
Abstract Traditionally dates is consumed as a rich source of iron supplement and the current research discuss the synthesis of silver nanoparticles (AgNPs) using methanolic seed extract of Rothan date and its application over in vitro anti-arthritic, anti-inflammatory and antiproliferative activity against lung cancer cell line (A549). FTIR result of synthesised AgNPs reveals the presence of functional group OH as capping agent. XRD pattern confirms the crystalline nature of the AgNPs with peaks at 38º, 44º, 64º and 81º, indexed by (111), (200), (220) and (222) in the 2θ range of 10-90, indicating the face centered cubic (fcc) structure of metallic Ag. HR- TEM results confirm the morphology of AgNPs as almost spherical with high surface areas and average size of 42 ± 9nm. EDX spectra confirmed that Ag is only the major element present and the Dynamic light scattering (DLS) assisted that the Z-average size was 203nm and 1.0 of PdI value. Zeta potential showed − 26.5mv with a single peak. The results of the biological activities of AgNPs exhibited dose dependent activity with 68.44% for arthritic, antiinflammatory with 63.32% inhibition and anti-proliferative activity illustrated IC50 value of 59.66 μg/mL expressing the potential of AgNPs to combat cancer.Resumo em Inglês:
Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.Resumo em Inglês:
Abstract Periodontitis is an oral disease associated with inflammation and pain with swollen and bleeding gums. In the present study, dental pastes containing NSAIDs, namely, diclofenac sodium and nimesulide (1 % w/w) were prepared to treat periodontitis. Dental pastes of diclofenac sodium and nimesulide (1 % w/w) were prepared with/without mucoadhesive hydrocolloid polymers such as sodium carboxy methyl cellulose (NaCMC), hydroxyl ethyl cellulose (HEC) and methyl cellulose (MC) by conventional trituration method. The pH, drug content, viscosity, tube spreadability and tube extrudability of these prepared dental pastes were measured. These dental pastes of diclofenac sodium and nimesulide (1 % w/w) were characterized by FTIR analyses for drug-excipient compatibility. The in vitro drug releases from these dental pastes in 6.4 pH phosphate buffer solution displayed sustained release over longer period and the drug release rate was found to be decreased when the concentration of mucoadhesive polymer was increased. These dental pastes displayed good adhesion to the oral mucosa revealing more retention time in mouth when tested for ex vivo mucoadhesion using bovine cheek pouch. The stability study results reveal that the DC3 and NC3 dental paste formulations were found stable enough over a longer period in different storage conditions. The present study revealed that the prepared mucoadhesive dental pastes of diclofenac sodium and nimesulide (1 % w/w) had good adhesion with the oral mucosa to maintain consistent release of drugs over prolonged time.Resumo em Inglês:
Abstract Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.Resumo em Inglês:
Abstract The aim of present study was calculate the Minimum inhibitory concentrations (MICs) of silver nanoparticles and clotrimazole for Candida species and their interaction by the adaptation of standarized methods. The MICs values of clotrimazole were 9 E-04-3 E-03 ug/ml, 0.1-0.6 ug/ml, 3 E-03- 0.1 ug/ml and 3 E-03-0.3 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. The MICs values of silver nanoparticles were 26.50- 53 ug/ml; 26.50-106 ug/ml; 106-212 ug/ ml and 26.50- 53 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. Synergism between clotrimazole and silver nanoparticles was measured by checkerboard BMD (broth microdilution) test and shown only for C. albicans susceptible to fluconazole because the fractional inhibitory concentrations (FICs) values were 0.07 - 0.15 ug/ml. Indifference was shown for the other species tested because the FICs values were between 0.5 - 2- 3.06 ug/ml. The results suggest synergistic activity depending on the fungus species analysed, however we recommend the incorporation of others measurement methodologies to confirm our results. As for measurement methodologies of MICs of silver nanoparticles and clotrimazole international normative were respected to guarantee reproducible and comparable results.Resumo em Inglês:
Abstract There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.Resumo em Inglês:
Abstract The hepatoprotective potential of alcesefoliside (AF) from Astragalus monspessulanus was investigated. Iron sulphate/ascorbic acid (Fe2+/AA) lipid peroxidation was induced in rat liver microsomes and pre-incubated with AF and silybin (100, 10 and 1 µmol). Pronounced effects were observed in 100 µmol. In vivo experiments were carried out on rats, challenged orally with carbon tetrachloride (CCl4) alone and after pre-treatment and followed by curative treatment with AF (10 mg/kg). The activity of the serum and antioxidant enzymes, together with reduced glutathione (GSH) levels and malonedialdehyde (MDA) quantity were measured. Microsomal incubation with Fe2+/AA increased MDA production. The pre-incubation with AF reduced the formation of MDA, comparable to silybin. These findings were supported by the in vivo study where CCl4-induced liver damage was discerned by significant increase in serum enzymes and in MDA production as well as by GSH depletion and reduced antioxidant enzymes activity. The AF pre-treatment and consecutive curative treatment normalizes the activity of the serum and antioxidant enzymes alike, as well as the levels of GSH and MDA. Histological examination of AF-treated livers showed a decrease in the abnormal accumulation of lipids in hepatocytes as well as reduced alterative changes in their structure in a model of CCl4-induced toxicity.Resumo em Inglês:
Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.Resumo em Inglês:
Abstract The objective of this study was to evaluate drug interactions based on medical records of patients hospitalized in University Hospital Lauro Wanderley (UHLW) in João Pessoa-PB, Brazil. This was a quantitative, descriptive study with a cross-sectional design. This research was conducted in the medical clinic of the above hospital by analyzing pharmaceutical intervention in medical records. The investigated samples consisted of all medical profiles with drug interaction information of patients hospitalized from June 2016 to June 2017. Most of these drug interactions were determined and classified by Micromedex® Solutions database. This research was approved by the Ethics Committee in Institutional Human Research, protocol number 2.460.206. In total, 331 drug interactions were found in 131 medical profiles. Dipyrone, enoxaparin, sertraline, ondansetron, quetiapine, tramadol, bromopride, amitriptyline, and simvastatin were medications that showed highest interactions. According to Anatomical Therapy Classification (ATC), drugs that act on the central nervous system result in more interactions. The most prevalent interaction was between dipyrone and enoxaparin. Some limitations of this study are the lack of notifications and data on drug interactions.Resumo em Inglês:
Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.Resumo em Inglês:
Abstract Interferon-β-1a (INF-β-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-β-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-β- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-β-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-β-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- β-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO.Resumo em Inglês:
Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.Resumo em Inglês:
Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia.Resumo em Inglês:
Abstract Some plants of the genus Pulicaria have been used in traditional medicines for treating back pain and inflammation. They possess various bioactivities such as antipyretic, analgesic, and hepatoprotective. This study aimed to investigate the potential analgesic, antipyretic, anti- inflammatory, and hepatoprotective activities of Pulicaria crispa (P. crispa) extract (PCE). Analgesic activity was evaluated using the hot plate and acetic acid-induced writhing tests. Antipyretic and anti-inflammatory activities were evaluated using rectal temperature and carrageenan-induced hind paw edema methods, respectively. CCl4-intoxication was used for hepatoprotective activity. Also, liver histopathology was assessed. PCE, at 500 mg/kg, exhibited significant analgesic, antipyretic, and anti-inflammatory effects. The increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin of CCl4-exposed rats reflects their liver injury. PCE significantly decreased the elevated liver markers. The hepatoprotective effect of PCE was confirmed, as it successfully reversed the altered levels of total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) in the liver tissues of CCl4-exposed rats. Histopathological studies confirmed the hepatoprotective nature of PCE. Pretreatment of rats with PCE reduced the severity of CCl4-induced liver damage. These findings concluded that PCE possesses analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities.Resumo em Inglês:
Abstract The present study proposes and evaluates the test-retest reliability of indicators of the correct use of sodium alendronate in elderly patients. This is a test-retest reliability study for use of sodium alendronate. Six questions to evaluate the correct use of this medicine were elaborated after analysis of information in the literature. Data collection was performed through questionnaires in face-to-face in-home interviews by previously trained interviewers. The participants were initially interviewed (test) when they agreed to participate in the study, and secondly (retest), after a period of 7 to 14 days from the first interview. The reliability of the questions was evaluated by means of the agreement percentage and the Kappa coefficient. Fifty-seven pairs (test-retest) were obtained. The mean age was 69.3 (SD = 6.9) years, the majority (92.5%) completed elementary education, and declared themselves white (50.9%). All the questions presented high concordance ranging from 79.0% to 98.3%. The Kappa values ranged from 0.1 (low) to 0.83 (very good). The agreement percentage and the Kappa values suggest adequate reliability of the proposed questions. We suggest that they can be used as a simple and quick way to evaluate the quality of sodium alendronate use among the elderly.Resumo em Inglês:
Abstract The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor.Resumo em Inglês:
Abstract Persea americana Mill., belonging to the family Lauraceae, is noteworthy for the large amount of ethnopharmacological information in its regard, attributing to it many and varied medicinal properties. The tea and alcoholic extracts made from its leaves are used in folk medicine to treat various ailments. This study was designed to analyze the cytogenotoxicity and underlying chemistry of aqueous and hydroalcoholic extracts of avocado leaves, using the Allium cepa and micronucleus tests. The results obtained by applying the experimental models demonstrate that the extracts did not have a genotoxic effect at any of the concentrations analyzed, and even demonstrated a certain protective effect, possibly due to the presence of flavonoids and phenols, both of which are antioxidant substances. However, the extracts did present a cytotoxic effect. There were numerous karyorrhectic cells and those with nuclear alterations related to cell death. At the highest concentrations, it was possible to observe cytoplasmic alterations and binucleated cells. The extracts also caused a significant reduction in the number of cells undergoing division. These effects can be a response to the phytochemical agents present in the extracts. The results suggest that the extracts contain bioactive components that deserve further studies related to cancer therapies.Resumo em Inglês:
Abstract Stomach cancer is the second leading cause of death by cancer worldwide and is even more pronounced in South America. In Brazil, it is estimated that an increase in the number of cases due to this cancer occurred in the biennium 2018-2019. In this study, we investigated the expenditures of the State Health Department of Goiás on hospitalizations and treatment of gastric cancer for the Unified Health System (SUS) from 2008-2016. This is a cross-sectional, descriptive, and analytical study based on secondary data from the Unified Health System computing department (DATASUS) and the System of Management of the Table of Procedures, Medications, Orthosis, Prosthesis, and Special Materials of SUS through CONECTA-SUS related to International Classification of Diseases-10/C16 (ICD-10/C16) procedures for gastric neoplasms. A total of I$ 5,697,958.20 was spent on gastric tumor in the last nine years in Goiás, I$ 4,492,916.67 (0.3%) on hospitalizations, and I$ 1,997,120.91 on treatment. This study presents a current and relevant estimate of the costs of gastric cancer patients in Goiás. Moreover, we provide information on the extent of the cancer issue to public health. Our analysis offers components for service management and studies that reduce resource allocation in more rational ways.Resumo em Inglês:
Abstract Essential oils from four Ocotea species collected in southern Brazil were evaluated for chemical composition using gas chromatography coupled with mass spectrometry. The primary compound identified in O. acutifolia essential oil was an unsaturated tetracyclic diterpene, phyllocladene (67.7%), followed by a sesquiterpene hydrocarbon, β-selinene (18.0%). The sesquiterpene fraction was predominant in oils from two collections of O. puberula; β-caryophyllene (25.2%) and globulol (22.6%) were the major compounds identified in collections 1 and 2, respectively. O. silvestris essential oil contained predominantly germacrene D and bicyclogermacrene. These compounds were also predominant in essential oil from O. indecora leaves collected from shady habitats. By contrast, essential oil extracted from O. indecora grown under direct sunlight contained mainly oxygenated sesquiterpenes, such as guaiol (30.2%), α-eudesmol (27.6%), and β-eudesmol (12.7%). Chemotaxis assays showed that Ocotea essential oils had no significant inhibitory activity on leukocyte migration compared with a chemotactic stimulant (lipopolysaccharide from Escherichia coli). However, the oils exhibited antifungal activity against Candida parapsilosis, with a minimum inhibitory concentration of 500 µg/mL. To our knowledge, this is the first study to investigate the in vitro antifungal and antichemotactic activities of essential oils from Ocotea species native to southern Brazil.Resumo em Inglês:
Abstract The aim of this study was to investigate the effect of TiO2/N-succinyl-chitosan composite (TiO2/ NSCS) photodynamic therapy (PDT), while considering the effects of various light sources on the activation of photosensitizer. The methyl thiazolyl tetrazolium assay was used to examine the cell survival rate of the cells. The results showed that glioma cell strain (U251) was the most sensitive cancer cell strain to TiO2/NSCS. When the concentration of TiO2/NSCS was between 0 and 800 μg·mL-1, there was no obvious cytotoxicity to normal liver cells (HL-7702) and U251 cells. During the PDT process, the photokilling effect of TiO2/NSCS on U251 cells under ultraviolet-A (UVA) light irradiation was stronger than that of pure TiO2, and its killing effects were positively correlated with concentration and irradiation time. In addition, both UVA and visible light could excite TiO2/ NSCS, which had significant killing effect on U251 cells. The results of acridine orange/ethidium bromide fluorescent double staining and Annexin V/propidium iodide double staining indicated that TiO2/NSCS under UVA and visible light irradiation could kill U251 cells by inducing apoptosis, and the apoptosis rate of TiO2/NSCS treatment groups was higher than that of TiO2 treatment groups. Therefore, TiO2/NSCS might be used as a potential photosensitizer in PDT.Resumo em Inglês:
Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion.Resumo em Inglês:
Abstract The present study aimed to compare the crude, modified and hydrolyzed gums of Dalbergia sissoo and Acacia modesta as a biodegradable binder for drug delivery system using acetaminophen as a model drug. The physiochemical properties such as pH, fluorescence analysis and swelling index were determined. The gums were hydrolyzed and modified. Acetaminophen tablets were prepared using wet granulation technique and the gum solutions were used as a binder. Hydroxypropyl methylcellulose was used as a synthetic binder. Different properties of granules and tablets were evaluated. Results showed that both gums were acidic in nature, while D. sissoo and A. modesta showed light brown and creamy color in fluorescence analysis. The swelling ratio was the highest in water followed by 0.1N HCl and least in phosphate buffer. The prepared tablets showed faster and slower dissolution profiles in the same dissolution system. The crude gums have the highest dissolution rate, and this rate was decreased in the case of modified and hydrolyzed gums samples. The crude gums showing slower release can be useful in sustained-release tablets, while the modified gums having faster release rate are helpful in conventional tablet formulation. Taken together, the selected gums could be a good model for evaluation as a binder or hydrophilic polymer in tablet formulation.Resumo em Inglês:
Abstract In antimalarial research there are no standard procedures to determine the toxicity of a drug candidate. Among the alternatives available, in vitro cytotoxicity assays are the most widely used to predict toxic effects of future therapeutic products. They have the advantage over the in vivo assays, in that they offer the possibility to restrain the number of experimental variables. The objective of the present study was to compare in vitro cytotoxic methods by testing various compounds currently used to treat malaria against different cell lines. Neutral red (NR) uptake and methylthiazoletetrazolium (MTT) colorimetric in vitro assays were used to determine preliminary toxicity of commercially available antimalarial drugs against tumor and non-tumor cells lines. Toxicity through brine shrimp lethality bioassay and hemolytic activity were also evaluated. Significant differences were observed in the tests measured by NR uptake. The tumor cell lines TOV-21G and HepG2 and non-tumor WI-26VA4 cells showed relatively uniform toxicity results, with TOV-21G being the most sensitive cell tested, presenting the lowest concentration to cause death to 50% of viable cells (CC50) values. The results of this study support the use of TOV-21G, HepG2 and WI-26VA4 cells lines as the choice for cytotoxicity tests to evaluate potential bioactive compounds.Resumo em Inglês:
Abstract Fluoride anions are indispensable trace elements required for sustaining life. To investigate the homeostasis and action of fluoride in the body, a new highly sensitive and selective fluorescence detection method was designed for fluoride in aqueous solutions. A fluorescent probe for fluoride (FP-F) was synthesized for imaging F- in living cells. The design strategy for the probe was based on the specific reaction between fluoride and silica to mediate deprotection of this probe to fluorescein. Upon treatment with F-, FP-F, a closed and weakly fluorescent lactone, was transformed into an open and strongly fluorescent product. Under the optimum conditions, the detection limit for fluoride was 0.526 nM. FP-F could detect micromolar changes in F- concentrations in living cells by confocal microscopy.Resumo em Inglês:
Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 μm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction.Resumo em Inglês:
Abstract This study aimed to describe potentially inappropriate medication (PIM) use according to the Beers criteria among older adults followed in a comprehensive medication management (CMM) service, the pharmacists´ interventions, and the clinical outcomes of PIM use. All older adults in a CMM service delivered in the Brazilian public primary care system were included in the study (n = 389). Two methodological approaches were developed: (I) cross-sectional - prevalence of PIM use and associated factors were identified (univariate analysis - Pearson’s chi-square; multivariate - logistic regression); (II) documental analysis of the negative clinical outcomes potentially associated with PIM use and pharmacists’ interventions. The prevalence of PIM use was 48.3%, and it was independently and positively associated with the use of ≥ 5 drugs. For 21.3% of PIMs, a potential negative clinical outcome was identified. The most common negative clinical outcome was hypotension (35.1% of the negative outcomes), fractures or diagnosis of osteoporosis (21.1%), and hypoglycemia (14.0%). For most of them (78.9%), an intervention was performed to mitigate harm or discontinue use. A high prevalence of PIM was detected and was associated with polypharmacy. A significant proportion of PIM showed potential negative clinical outcomes that were identified by clinical pharmacists, and the majority of pharmacists’ interventions aimed at its mitigation or deprescription. Overall, our findings reinforce the potential of CMM services for reducing PIM use and the occurrence of negative outcomes.Resumo em Inglês:
Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.Resumo em Inglês:
Abstract This study examined the effects of pharmacist interventions for patients with advanced prostate cancer. A pre-post study was conducted between October 2014 and August 2017 in a community pharmacy in Brazil for outpatients with advanced prostate cancer, aged ≥ 18 years, using cyproterone acetate and/or goserelin. The patients had face-to-face meetings with a pharmacist who dispensed antiandrogenic drugs and performed interventions aimed at solving and/or preventing drug-therapy problems. Primary outcomes regarding prostate-specific antigen (PSA) and testosterone levels were compared at 0, 6, and 12 months, whereas secondary outcomes-medication adherence and quality of life-were compared at baseline and at the 12-month follow-up. Medication adherence was assessed using the Morisky-Green test, and quality of life was measured by the Medical Outcomes Study 36-item Short Form (SF-36) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The analysis included 20 patients; 311 drug-therapy problems were identified and most of them were related to adverse reactions (78.5%). The most common adverse reactions were reduced libido, erectile dysfunction, hyperglycemia, fatigue, and gynecomastia. Testosterone levels significantly decreased at 6 months, and PSA levels at 6 and 12 months. No significant changes in adherence were noted at the end of the study. A significant increase in the “pain” domain and an improvement trend in the “physical aspects” and “vitality” domains were observed based on the SF-36 instrument. The findings show that pharmacist interventions were able to improve PSA and testosterone levels, and some domains of quality of life of patients.Resumo em Inglês:
Abstract Medication errors (ME) are frequent in the admission of patients to the ICU and can be identified and prevented through medication reconciliation (MR). Our aim was to evaluate the incidence, type and severity of MEs and associated factors, identified during MR in the ICU. This is a prospective, analytical approach, performed in the ICU of a private hospital, where the MRs were evaluated from April to June 2016. The SPSS and Stata programs were used to analyse the data. Logistic regression was performed to determine the factors associated with MEs. MR was performed with 136 patients, of whom 126 (92.6%) used drugs regularly. The incidence of MEs was 16.3% (95% CI 11.5-21.2). The main classes of drugs involved were those acting on the nervous and cardiovascular systems. There were 128 pharmaceutical interventions (acceptance: 71.1%). Regarding severity, 65.5% (n=80) of the errors reached the patient, but there was no harm. The risk factors for MEs identified were: age ≥60 years, number of comorbidities >1 and previous use of drugs ≥9. The incidence of MEs found and the significant association with age, comorbidities and polymedication alert to the need for specific attention to prevent admission errors in the most susceptible patient groups.Resumo em Inglês:
Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.Resumo em Inglês:
Abstract Suitability of developing Spirulina incorporated cereal based low cost nutritious extrudates was analysed against extrusion processing parameters. Most significant extrusion processing parameters considered for present study were feed moisture (20-25%), die temperature (100-120 °C) and screw speed (50-100 rpm). Different extrusion conditions were used to obtain most acceptable rice: Spirulina blend extrudates. In present study before extrusion processing different additives (citric acid and sodium bicarbonate) were added in rice: Spirulina blend and checked its effect on colour degradation kinetics at varied packaging and storage conditions. Higher screw speed (100 rpm) indicating less residence time of feed material inside the barrel resulted in higher colour retention of rice: Spirulina (97:03) blend extrudates. Kinetics for rice: Spirulina (97:03) blend extrudates indicates faster rate of colour degradation in terms of lightness (half-life of 4 days) when packed in metalized polyethylene at 50°C with 65% relative humidity. Increased concentration of Spirulina (1-3%) in raw formulations resulted in increase in concentration of all amino acids. Impact of extrusion processing has shown non-significant (p ≤ 0.05) effect on amino acid concentrations of rice: Spirulina blend extrudates. Also, all the spirulina added samples showed good consumer acceptability with the score of 6.7.Resumo em Inglês:
Abstract Gout is a form of metabolic arthritis originated on grounds of increased accumulation of monosodium urate (MSU) crystals in joints. Current study focuses on anti-arthritic activities of β-carotene on MSU crystal-induced gouty arthritis rats in comparison with the non-steroidal anti-inflammatory drug, indomethacin. The evaluation was done by taking into account paw oedema, lysosomal enzymes, anti-oxidant enzymes, lipid peroxidation, serum biochemical parameters (uric acid, creatinine), serum cytokines (TNF-α, IL-1β) and histopathological studies. After the induction of MSU crystals, the lysosomal enzymes were increased, antioxidant enzymes were reduced, lipid peroxidation increased and paw volume increased. β-carotene treated at a dose of 10 mg/kg of body weight stabilizes lysosomal enzymes, increases anti-oxidant enzymes, regulates lipid peroxidation and decreased paw volume. The drug β-carotene potentially influences anti-inflammatory effects in arthritic group which is evident from the reduction in the elevated levels of inflammatory cytokines, TNF-α and IL-1β. Current study is an evidence of anti-inflammatory and anti-oxidant effects of β-carotene against MSU-crystal induced gouty arthritis rats.Resumo em Inglês:
Abstract The objective of this work is to reflect on the objects and approaches usually employed in the evaluation of pharmaceutical care and their potential applicability in primary care settings. We conducted the review of the literature, and, to exemplify the advantages of expanding these objects and approaches, a real-world problem situation was selected: morbidity and mortality related to lack of treatment adherence by hypertensive patients in Brazilian primary health care services. Our reflections highlight the need to evaluate the effects of interventions, understood within Donabedian’s normative model as ‘outcomes,’ which can be clinical, humanistic, or economic. Our findings show that most published studies, even those that set out to report outcomes, actually evaluate processes, such as number of visits, number of problems identified, types of problems, or acts of the practice performed by pharmacists. On the other hand, we also identify a need for study designs and indicators to enable ‘finer’ normative assessment. We also discuss the importance of shifting research toward an evaluative paradigm to allow strategic, logic, effects, production, efficiency, and implementation analyses. Finally, we suggest some possible indicators to evaluate pharmaceutical care interventions in the selected problem situation, through an extension of the objects and approaches proposed.Resumo em Inglês:
Abstract Most chronic kidney disease inevitably progress to renal fibrosis. Tubular epithelial- to-mesenchymal transition (EMT) is recognized to play major roles in renal fibrosis. Oxymatrine (OM) is a major alkaloid component found in a Chinese herb Sophora roots and has many effects. The aim is to investigate the effect of OM on renal tubular EMT and elucidate its mechanism. Mice underwent unilateral ureteral obstruction (UUO) followed by intraperitoneal injection of OM (120 mg/kg) or control vehicle. Human kidney proximal tubular cell line (HK-2) was used and EMT was induced with 5 ng/mL of transforming growth factor-β1 (TGF-β1). In vivo, renal tubulointerstitial fibrosis was induced and E-cadherin was down-regulated, while the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), TGF-β1 and its type I receptor (TGF-βRI) were up-regulated in UUO mice. In contrast, OM significantly ameliorated renal fibrotic lesions and attenuated the expressions of FN, α-SMA, TGF-β1 and TGF-βRI, but increased E-cadherin in the obstructed kidneys. In vitro, OM abolished TGF-β1-mediated E-cadherin suppression and FN, α-SMA and TGF-βRI induction in HK-2 cells in a dose-dependent manner. These observations strongly suggest that the renal protective effects of OM could be mediated by prevention of EMT and manifested as suppression of TGF-β1 and TGF-βRI expressions.Resumo em Inglês:
Abstract The continuous prolonged exposures of sun light especially the ultra violet (UV) radiation present in it, cause not only the risk of skin cancer but also it may cause premature skin aging, photodermatoses and actinic keratoses. Flavonoids (including Flavane, Flavanone, Flavone, Flavonol, Isoflavone, Neoflavone etc.) having potent antioxidant activity, used as topical applications for protection against UV induced skin damages as well as for skin care. Most commonly used flavonoid is quercetin (Flavonol), which is present in fruits, vegetables, and herbs. We aim to review the research focused on development of different novel formulations to treat UV radiations induced skin diseases. In this review, several formulations of flavonoid quercetin were discussed and their outcomes were compiled and compared in context to solubility, stability and efficiency of application. On the basis this comparative analysis we have concluded that three formulations, namely glycerosomes, nanostructured lipid carriers and deformable liposomes hold good applications for future aspects for topical delivery of quercetin. These formulations showed enhanced stability, increased quercetin accumulation in different skin layers, facilitated drug permeation in skin and long-lasting drug release.Resumo em Inglês:
Abstract Phenolic compounds are widely distributed in the plant kingdom and in the microorganisms. Cinnamic acid and its hydroxylated derivative-ferulic acid, are phenolic compounds. Ferulic acid possesses antioxidant potential, as well as anti-cancer, anti-inflammatory, and antimicrobial properties. It prevents the harmful effects of radiation both as an ultraviolet absorber and as a free radical scavenger; it is not cytotoxic. Although ferulic acid has beneficial properties, it is hardly used in cosmetic preparations and has been rarely studied in the literature. Herein, we review the literature on ferulic acid, to provide information which can contribute to further research on the compound.Resumo em Inglês:
Abstract Phoenix dactylifera L. has traditionally been used as a medicine in many cultures. The aim of this study was to evaluate the nutritional properties, aromatic compounds, total phenolic content and the antioxidant activity of ten ripe date fruit varieties grown in Tunisia. Sugar profiles were analyzed by high performance liquid chromatography, while fatty acid compounds were detected by gas chromatography and aromatic compounds were analyzed by GC-Electron Impact Mass Spectroscopy. Total phenolic contents were measured using colorimetric methods, whereas antioxidant capacities were evaluated in vitro using DPPH and ABTS radicals. It has been found that total sugars are the predominant component in all date varieties, followed by moisture, along with moderate amounts of proteins, ash, and fats. Multivariate tests based on the volatile compounds profile showed significant differences among varieties. Between the sixty-two volatile compounds detected, alcohols, aldehydes and unsaturated hydrocarbons constituted the main chemical classes. The date varieties exhibited strong antioxidant potential that correlated with phenolic content. In conclusion date varieties can play a major role in human nutrition and health because of their wide range of valuable nutritional components and natural antioxidants that could potentially be considered as a functional food ingredient.Resumo em Inglês:
Abstract Hypoxia-inducible factors (HIFs) and cancer stem cells (CSCs) are two challenging causes of radiotherapy and chemotherapy resistance, leading to most cases of failure and recurrence in breast cancer therapy. This study was conducted to investigated the inhibitory effect of combination therapy with doxorubicin (an anthracycline) and FM19G11 (an HIF inhibitor) on MCF-7 cells and their CSC-like cells (CSC-LCs). MCF-7 CSC-LCs with a CD44+/CD24- phenotype were sorted and characterized by flow cytometry. A combination of doxorubicin and FM19G11 caused more cytotoxic effects on MCF-7 and CSC-LCs compared to doxorubicin monotherapy. The largest synergistic effect was observed in CSC-LCs under hypoxic conditions; however, MCF-7 cells showed no synergism in normoxic conditions. The administration of doxorubicin and FM19G11 induced late apoptotic and necrotic cell death in MCF-7 and CSC-LCs. Additionally, G2 phase arrest was observed in both cells. Our results demonstrated that co-administration of FM19G11 and doxorubicin had a synergistic effect in hypoxia and improved drug resistance in breast cancer stem cells.Resumo em Inglês:
Abstract It remains unclear whether increased inflammatory and cardiovascular risk biomarkers differ depending on the class of antiretroviral that is used. This study evaluated the plasma levels of inflammatory and cardiovascular risk biomarkers, such as MPO, hs-CRP, glucose, lipid profile, ALT (GPT), AST (GOT), urea and creatinine, as well as the blood count, of all the 164 participants in the study, either infected or un-infected with HIV. Thirty of the 104 HIV-infected individuals did not receive any antiretroviral; twenty-four of them were treated with non-nucleoside reverse transcriptase inhibitor class; and fifty took protease inhibitors. The control group consisted of sixty non-HIV infected individuals. In the case of the HIV-infected volunteers, the CD4+ T lymphocyte counts and viral load were also analyzed. Regardless of the hematological and biochemical changes resulting from the antiretroviral therapy (ART), the MPO and hs-CRP values significantly increased for the HIV-infected individuals (treated or untreated), irrespective of the class of ART that was used. This is important because these biomarkers are designed to be predictors of the risk of cardiovascular disease. The results of this study provide supporting evidence for the hypothesis that HIV-infected individuals are at increased risk of developing cardiovascular disease related to chronic inflammations, despite virological control with ART, and regardless of the class of ART that is used.Resumo em Inglês:
Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.Resumo em Inglês:
Abstract Recently, the acetate wheat starch (AWS) has been prepared by acetylation with an acetyl content of 2.42%, containing of rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS) with 25.0%; 22.9% and 34.5%, respectively. In this study, this kind of starch was continuously evaluated with the postprandial blood glucose response and determined short-chain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. The result showed that the mice fed with AWS exhibited a very limited increase in blood glucose level and remained stable for 2 hours after meals efficiently comparing with the control group fed with natural wheat starch (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed with AWS was significantly higher than mice fed with NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Thus, AWS has shown to limit the postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs providing a part of energy for the body’s activities, avoiding rotten fermentation causing digestive disorders which are inherent restrictions of normal high cellulose and fiber food.Resumo em Inglês:
Abstract The extract of Belamcanda chinensis leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of diabetes-related hyperlipidemia in Hainan province, South China. In this study, the lipid-decreasing effects of BCLE on obese diabetes were investigated on KK-Ay mice. The component F2 ameliorated lipid disorder, as indicated by decreased levels of body weight, liver index, levels of TC, TG and LDL-c in the serum and liver. The enhancement effect of F2 on liver SOD and the inhibitory effect of F2 on MDA demonstrated that F2 exhibited significant antioxidant activity on liver injury. F2 also prevented vacuolar degeneration and reduced pathological tissue injury in liver. In addition, the component F1 decreased the levels of TG, LDL-c and MDA in the liver. These findings suggest that F2 may have therapeutic potential in the prevention and therapy of hyperlipemia and liver disease associated with obesity-related diabetes.Resumo em Inglês:
Abstract Dialysis has been widely used in the treatment of patients with chronic kidney diseases and is considered a global public health issue. This treatment, which has changed the prognosis and quality of life in patients with chronic renal failure, can lead to complications that are often fatal. For this reason, there is a need for validation of alternative tests that favor the monitoring of treated water for dialysis in real-time to promote and prevent injuries to patients submitted to this procedure.Resumo em Inglês:
Abstract The present study was designed to examine the effects of atorvastatin on vascular inflammatory responses in human coronary artery endothelial cells(HCAECs), when challenged by lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) ligand. HCAECs were pretreated with atorvastatin and induced by LPS. The expression of TLR4, interleukin -6(IL-6), monocyte chemoattractant protein 1(MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecular-1(ICAM-1), nuclear factor-κB (NF-κB) and p38 mitogen activated protein kinase(p38 MAPK) were evaluated using Real-time polymerase chain reaction, cytokine ELISA assay and Western blotting. The results showed that pretreatment with atorvastatin down-regulated the expression of TLR4 in LPS-activated HCAECs. Atorvastatin also attenuated the LPS-induced expression of interleukin IL-6 and MCP-1, at both the transcription and translation level in HCAECs. LPS-induced endothelial cell adhesion molecules, ICAM-1 and VCAM-1 expression were also reduced by pretreatment with atorvastatin. Furthermore, atorvastatin efficiently suppressed LPS-induced phosphorylation of NF-κB and p38 MAPK in HCAECs. These findings show that atorvastatin suppresses endothelial cell inflammation, suggesting that atorvastatin may be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.Resumo em Inglês:
Abstract We aimed to determine the effects of boric acid and quercetin on contrast media-induced nephropathy in rats. Thirty-two rats were divided into four equal groups with eight rats in each group: the control (C) group, contrast media (CM) group, contrast media plus boric acid (CMB) group, and contrast media plus quercetin (CMQ) group. Boric acid (H3(BO)3, 4% solution) at a dose of 200 mg/kg was administered by oral gavage to rats in the group CMB once daily for 4 consecutive days (days 1 to 4). Quercetin at a dose of 50 mg/kg was administered by oral gavage to rats in the CMQ group once daily for 4 consecutive days (days 1 to 4). A significant decrease was found in the serum urea and creatinine levels in the CMQ group compared with the CM group (P <0.01). The serum nitrite and nitrate levels were higher in the CM group than in the C group and were lower in the CMQ group than in the CM group (P <0.01). A significant decrease in the severity of tubular necrosis was found in the CMQ group compared to the CM group (P <0.05). Quercetin had protective effects against contrast nephropathy, but no beneficial effect of boric acid was found.Resumo em Inglês:
Abstract Alzheimer’s disease (AD) is a neurological disorder in which the neuronal degeneration is associated with inflammatory processes and oxidative stress. Since alpha-terpineol was shown to possess antioxidant and anti-inflammatory effects, the administration of this compound was studied on a rat model of AD. To create this model, Aβ1-42 was injected into the hippocampus of male Wistar rats. Generated AD models were divided into simple AD models and AD models in which short-term immobilization stress was added. Preventive and therapeutic (post-AD induction) effects of alpha-terpineol consumption (100 mg/Kg) were subsequently investigated in AD models, which were compared with control groups. Biochemical factors (superoxide dismutase and malondialdehyde), histological manifestations (amyloid plaques and neuron counts) and possible memory impairment (shuttle-box experiment) were investigated in all groups. For the in vitro experiment, alpha-terpineol effect was checked on Aβ1-42 fibril formation. In preventive and therapeutic modes, alpha-terpineol consumption could improve neurogenesis and long-term memory while reducing amyloid plaque counts and ameliorating biochemical factors (higher levels of superoxide dismutase and malondialdehyde and reduced levels of MDA). In vitro, shorter fibrillar structures were formed in the presence of alpha-terpineol, which indicates an anti-amyloid effect for this compound. In conclusion, alpha-terpineol significantly counteracted AD consequences.Resumo em Inglês:
Abstract Piper sarmentosum is a herbaceous shrub with numerous pharmacological benefits. However, the presence of two toxic phenylpropanoids (α- and β-asarone) limits the medicinal usage of the plant. In this study, the extraction of three asarone isomers, namely α-, β-, and -asarone was optimised using supercritical carbon dioxide extraction (SC-CO2) combined with Box-Behnken experimental design. Comparison of asarone contents in different conventional solvent extracts of P. sarmentosum leaves prior to and after SC-CO2 extraction was performed. The SC-CO2 method successfully maximised the extraction of α-, β-, and ɣ-asarone at P = 81.16 bar, T = 50.11°C, and t = 80.90 min, yielding 13.91% α-asarone, 3.43% β-asarone, and 14.95% ɣ-asarone. The SC-CO2 residue of the leaves re-extracted with conventional solvents showed a significant decrease of asarone ranging from 45% to 100% (p<0.001) compared to their counterparts without SC-CO2 treatment. α-, β-, and ɣ-asarone were completely removed in the ethanol extract of the residue. These findings suggested that the optimised SC-CO2 extraction parameters may serve as a quick treatment step for the selective removal of asarone from P. sarmentosum to develop safer extracts for the food and nutraceutical industries applications.Resumo em Inglês:
Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff’s apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.Resumo em Inglês:
Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.Resumo em Inglês:
Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.Resumo em Inglês:
Abstract Thiazolidinedione, often shortened to TZD or glitazone, helps lower insulin resistance, which is the underlying problem for many people with type 2 diabetes. The two most known glitazones are pioglitazone (PGZ), with the brand name medicine Actos®, and rosiglitazone (RSG), which is Avandia®. This study presented a multivariate optimization in the microextraction procedure employing Fractional Factorial Design (FFD) combined with Desirability Function (DF) to determine TZD and metabolites in biological samples. Microextraction requires several parameters to be optimized; however, most of them still use univariate optimization. Finding optimum conditions by simple response is relatively simple, but the problems, in case of microextractions, are often more complex when it has more responses. For example, changing one factor that promotes one response may suppress the effect of the others. Thus, this multivariate optimization was applied for two bioanalytical methods for determination of TZD and metabolites, one by HPLC and other by CE, both using Hollow Fiber Liquid-Phase Microextraction (HF-LPME). The results establish the optimal values and elucidate how the factors that affect HF-LPME procedure perform in extraction efficiency for TZDs. Additionally, this study demonstrates that DF can be an important tool to optimize microextraction procedures.Resumo em Inglês:
Abstract In this work, polystyrene-b-poly (acrylic acid) (PS-b-PAA) nanovesicles were coated by modified chitosans aiming at studying its physicochemical parameters. The chitosan (CS) was chemically modified to add hydrophilic and/or hydrophobic groups, obtaining three modified chitosans. The PS-b-PAA nanovesicles were obtained by organic (1,4-dioxane) cosolvent method in water, resulting in nanovesicles with less than 150 nm of diameter (polydispersibility index - PDI at 90° = 0.106), measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and negative zeta potential (-37.5 ± 3.2 mV), allowing the coating of its surface with oppositely charged polysaccharides, such as the CS and the modified chitosans. The coating process was made by mixing the colloidal suspensions with the CS and the modified chitosans at specific ENT#091;CS-xENT#093;/ENT#091;PS-b-PAAENT#093; ratios (0.001 to 1.0 wt %) and measuring the change in size and surface charge by DLS and zeta potential. Upon reaching maximum adsorption, the zeta potential parameter was positively stabilized (+26.7 ± 4.1 mV) with a hydrodynamic diameter slightly longer (< 200 nm of diameter). The encapsulation efficiency (EE) of minoxidil, quantified by capillary electrophoresis, was 50.7%, confirming their potential as drug delivery carriers and the coating process showed the possibility of controlling the surface charge nature of these nanovesicles.Resumo em Inglês:
Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.Resumo em Inglês:
Abstract The chemically complex essential oils of Baccharis species are associated with several biological activities, such as antimicrobial and antiulcerous properties. However, few studies have investigated Baccharis erioclada DC. Therefore, in this study, we aimed to characterize the essential oil of B. erioclada and evaluate its antioxidant, antimicrobial, and hemolytic potential. The essential oil was extracted by hydrodistillation using a Clevenger apparatus and analyzed via gas chromatography-mass spectrometry (GC-MS). Phosphomolybdenum complex formation, reducing antioxidant power, and thiobarbituric acid reactive substances (TBARS) methods were used to determine antioxidant potential. To evaluate the essential oil’s antimicrobial activity, minimum inhibitory concentrations (MIC) in Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were calculated. Hemolytic activity was determined in sheep red blood cells. Thirty-one compounds were identified via GC-MS analysis, representing 81.60% of the total essential oil. These compounds included: turmerone (27.97%), fokienol (13.47%), ledol (9.78%), and santalol (5.35%). The class of compounds identified was the oxygenated sesquiterpenes (62.52%). Antioxidant activity was confirmed via phosphomolybdenum complex formation and TBARS methods. Moderate antimicrobial activity and low hemolysis rates were displayed at concentrations of 250 and 500 μg/mL.Resumo em Inglês:
Abstract Nanotechnology has been used in the field of medicine and pharmacology for its greater efficacy of drug delivery than crude molecules of drugs. In the present study medicinal mushroom Ganoderma applanatum extract mediated silver nanoparticles (AgNPs) were synthesized, characterized by Ultraviolet-visible (UV-Vis.) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction, Dynamic light scattering (DLS) and Furior transform-infrared (FTIR) spectroscopy. Maximum absorbance was recorded at 435nm by UV-Vis. The synthesized nanoparticles of 13.54nm-255nm in size with an average particle size of 58.77nm were analyzed by DLS. FTIR-Spectroscopy provided high transmission at 3606cm-1 corresponds for phenolic capping biochemical. Thus G. applanatum extract can be used for synthesis of silver nanoparticles and the synthesized nanoparticles may be used for development of future therapeutic agent for treatment of diseases.Resumo em Inglês:
Abstract The aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation.Resumo em Inglês:
Abstract In the present study, the metabolite profiling of methanolic extract from aerial parts of Satureja khuzistanica Jamzad, as an endemic medicinal plant from Iran, was evaluated using HPLC-PDA-ESI. Then, the main compound from the extract was isolated and purified by using extensive chromatographic techniques. In addition, the structure of the isolated compounds was elucidated using 1D, 2D NMR, and MS spectrometry, upon which 22 compounds were identified. The antibacterial activity of diosmetin 7-rutinoside (6) and linarin (13) in combination with carvacrol as a major compound of the essential oil was tested against Pseudomonas aeruginosa and Staphylococcus aureus through disc diffusion and minimum inhibitory concentration methods. The results indicated that the linarin, when mixed with carvacrol as the main compounds in the essential oil of the plant, has a satisfactory activity against both Pseudomonas aeruginosa and Staphylococcus aureus with MIC values of 0.16 and 0.18 µg/mL, respectively. Further, the fractional inhibitory concentration (FIC) index indicated that this compound had synergism with carvacrol.Resumo em Inglês:
Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.Resumo em Inglês:
Abstract This study investigates the toxic effects of ethanol (Eth) on the reproductive system of male rats and the possible protective role of Silybum marianum seeds-infused solution (SMI) over six consecutive weeks of administration. Animals were divided into the following groups: control, SMI positive control (200 mg/kg/day), Eth1 (1 g/kg/day), Eth2 (2 g/kg/day), Eth1+SMI, and Eth2+SMI. Plasma testosterone concentration, epididymal spermatozoa biology, and testicular and epididymal MDA, GSH and GPx levels were evaluated. The results indicated a significant decrease in testis and epididymis weight, testosterone level, sperm concentration, sperm vitality and sperm motility (total motility, progressive motility, curvilinear velocity, straight-line velocity, velocity average path, beat cross frequency, and lateral head displacement) in both Eth1 and Eth2 compared to the control groups and the combined-treatment groups (Eth1+SMI and Eth2+SMI). Furthermore, results showed a significant elevation in MDA concentration with a significant decrease of testicular and epididymal GSH concentration and GPx activity in theEth1 and Eth2 groups compared to the combined-treatment groups. The administration of SMI succeeded in improving the parameters cited above in the combined-treatment groups compared to the Eth1 and Eth2 groups, and bring them to the levels seen in the control groups. To conclude, SMI has clearly protected reproductive indices against ethanol-induced reprotoxicity in male ratsResumo em Inglês:
Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.Resumo em Inglês:
Abstract To analyze microbiological effectiveness of vancomycin in children from a pediatric hospital through population pharmacokinetic modelling, as well as to propose dose adjustment, a cross- sectional study was performed in children under vancomycin treatment from the John Paul II Children’s Hospital, MG. In order to establish a model, concentrations versus time curves were analyzed using a population pharmacokinetic approach with Pmetrics®. Seventeen blood samples of 10 patients were collected. The best model to describe vancomycin population pharmacokinetic (PK) consisted of a two-compartment linear intravenous absorption model. The R² value and bias for population and individuals in observed versus predicted plot was 0.642 vs. 0.992 and the bias of 0.41 mg/L and 0.0778 mg/L, respectively. The covariables creatinine clearance, age, and body mass index were related to vancomycin PK. A relevant PK variability for vancomycin in pediatric patients was verified, which was significantly influenced by creatinine clearance, age, and body mass index. This result justifies the formulation of dosing recommendations for vancomycin in pediatric patients to achieve adequate pharmacodynamics targets.Resumo em Inglês:
Abstract Oral delivery of antipsychotic drugs like Ziprasidone HCl has a disadvantage of gastric disturbance and lack of adherence to the treatment. In the present study, Ziprasidone HCl loaded ethosomal gel was formulated to avoid the disadvantages of oral delivery. The ethosomes were prepared using Lipoid S 75 with Isopropyl alcohol and Propylene glycol as the solvents. The formulated ethosomes were evaluated for different parameters like particle size, poly dispersibility index and entrapment efficiency. Based on diffusion studies, optimized ethosomal formulation was incorporated in carbopol 934 gel base. The final dosage form of ethosomal gel was evaluated for physical characteristics, drug content and proceeded with ex- vivo skin permeation studies. The maximum percentage of drug permeated after 24 hours was found to be 93.30±0.168. The flux was found to be 52.05± 0.564µg/hr/cm2. From the kinetic model fitting results, it was concluded that the ethosomal gel followed the first order kinetics and the higher “R2” values of the Korsmeyer Peppas model (R2=0.934, n=0.54) indicate that the encapsulating polymer is the responsible factor in controlling the release of the drug. The ethosomal gel loaded with ziprasidone HCl improves the bioavailability of ziprasidone HCl as well as surpassing drawbacks with oral delivery.Resumo em Inglês:
Abstract For the first time, five known metabolites - 1 and 5 are reported from the ethyl acetate extract from seaweed Chara baltica (EAE). Both the metabolites and EAE were screened against free- radicals, α-glucosidase enzyme and glycaemia in albino rats. 4, 5 and EAE depicted significant antiradical and α-glucosidase inhibitory profile. Particularly, compound 5 showed equivalent inhibition of superoxide free radical as that of the standard drug with IC50 value of 32.0 µg/mL. In addition, the EAE (200 mg/kg b.w) revealed significant reduction in plasma glucose, body weight, total cholesterol, total glycerides and LDL levels in Streptozotocin-induced diabetic rats. The HDL levels were markedly augmented in EAE treated diabetic rats, when compared with control group. EAE abolished the increased lipid peroxidation content in both liver and kidneys. The histopathological examination of pancreas of EAE protected the Langerhans islets with the number of islet cells were found statistically significant, when compared to diabetic control pancreas. This is the first in vitro and in vivo antidiabetic report on C. baltica.Resumo em Inglês:
Abstract Lagopsis supina (Steph) IK. Gal. was a traditional Chinese medicinal plant for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuresis with little scientific validation. The aims of this study were first to evaluate the PBCRBS and anti-inflammatory effects of L. supina in a rat model of traumatic blood stasis (TBS). We demonstrated that an ethanolic extract of L. supina (LS, 460 mg/kg/d) possessed significant PBCRBS and remarkable inhibitory effect on inflammation cytokines, which were associated with renovated amount of the injured muscle fibers, alleviate the degree of the damaged tissue edema, decreased the number of inflammatory cells, increased the number of the capillary hyperplasia by hematoxylin and eosin (HE), as well as remarkably down-regulated ( p < 0.05 or p < 0.01) the levels of inflammation cytokines, including TNF-α, IL-6, IL-8, and IL-10 by ELISA. This finding provide a pharmacological basis and partial interpretation for the clinical application of L. supina, which has therapeutic properties for blood stasis syndrome (BSS) and inflammation-related diseases.Resumo em Inglês:
Abstract It has been shown that an increase in cAMP leads to pain sensitization and gabapentin is shown to decrease cAMP levels. However, the impact of drugs modulating cAMP levels on analgesic actions of gabapentin is not studied. The present study investigates the effect of milrinone on pain attenuating effects of gabapentin in chronic constriction injury (CCI). Neuropathic pain was induced by putting four loose ligatures around the sciatic nerve. The pain assessment was done by noting the paw withdrawal threshold in the pinprick test, paw withdrawal latency in hot plate test and paw withdrawal duration in acetone drop test before surgery and on 14th- day post-surgery. There was a significant development of cold allodynia, mechanical and heat hyperalgesia on 14th day in CCI rats. Gabapentin (100 mg/kg) treatment for 14 days significantly attenuated pain, while milrinone (50 mg/kg) treatment for 14 days significantly exacerbated neuropathic pain in CCI-subjected rats. Milrinone (30 and 50 mg/kg) also attenuated analgesic actions of gabapentin in CCI-subjected rats, suggests that gabapentin may abolish neuropathic pain by increasing the intracellular levels of cAMP in CCI-subjected rats.Resumo em Inglês:
Abstract Here we examined whether serum from obese patients could create a growth-enhancing microenvironment that alters gene expression in BRAF- and NRAS-mutated melanoma cell lines. SK-Mel-28 (BRAF-mutated) and Sk-Mel-147 (NRAS-mutated) cells were treated with pooled serum from 10 severely obese patients (BMI > 40 kg/m2), pooled serum from 6 healthy lean individuals (BMI = 18.5-24.9 kg/m2), or recombinant TNF-α. We found that obese patient serum enhanced migration capacity and increased NRAS expression levels in both BRAF- and NRAS-mutated melanoma cells. Although TNF-α is the major obesity-related cytokine and TNF-α levels were found to be increased in the serum of obese individuals, this cytokine made only a modest contribution to the migration capacity of melanoma cells. These results indicate that other components present in the serum of severely obese patients may be responsible for enhancing the migration capacity of melanoma cells. As TNF-α alone did not seem to significantly affect tumor cell behavior, anti-tumor strategies aimed at blocking TNF-α should be considered with caution in future studies, particularly when in vitro models are used as screening platforms for antitumor activity.Resumo em Inglês:
Abstract The objective of this study was to trace the profile of patients with Ankylosing Spondylitis treated at the Pharmacy of the 9th Regional Health Department of Paraná and evaluate the relationship between pharmacological treatment, quality of life and disease activity index of these patients. Data collection was performed through interviews, application of BASDAI index and the ASQoL questionnaire. Male patients presented better rates (ASQoL 7.78 ± 6.04, BASDAI 4.26 ± 2.40) than female patients (ASQoL 12.08 ± 4.74, BASDAI 6.25 ± 2.43; p <0.05). Retired patients had higher disease activity and lower quality of life (BASDAI 6.59 ± 1.53, ASQoL 14 ± 2.89) than those who still worked (BASDAI 4.59 ± 2.87, ASQoL 7.68 ± 5.74); p <0.05), and the quality of life of patients with comorbidity (ASQoL 11.60 ± 5.47) was lower when compared to those without comorbidity (ASQoL 6.83 ± 4.90, p <0.05). Patients who used immunobiological drugs had better results (ASQoL 9.07 ± 5.86, BASDAI 4.73 ± 2.55) than those who used other drugs (ASQoL 13.08 ± 3.7, BASDAI 6.88 ± 2.15, p <0.05), and patients who used adalimumab showed better rates (ASQoL 7.42 ± 4.81, BASDAI 4.26 ± 2.47; p <0.05) when compared to other pharmacological treatments. Male patients showed a better response when compared to the female counterparts. Patients using adalimumab had a better quality of life and disease activity index than patients using other pharmacological treatments.Resumo em Inglês:
Abstract Chronic Lymphocytic Leukemia (CLL) has shown great biological heterogeneity, with a variable prognosis, and a short survival in some patients. In this light, the present study focused on the prognostic utility of circulating microparticles (MPs) and a Thrombin Generation (TG) Profile for thrombotic risk and disease progression in CLL patients. Circulating microparticles and TG were evaluated in 35 patients with CLL and 35 healthy individuals. For circulating microparticles, significant differences were observed among the following groups: MPs derived from endothelial cells (p = 0.002), B lymphocytes (p < 0.001), platelets (p = 0.003), and Tissue Factor MPs in monocytes (p < 0.001). In all cases, MP values were higher for the CLL group. When compared to the controls, CLL patients presented a decrease in TG, characterized by a reduced endogen thrombin potential (ETP) (p = 0.031). When the results were analyzed according to the Binet stage, as compared to the controls, the Binet B+C group also presented lower ETP values (p = 0.009). No significant differences were observed between the control and the Binet A groups or between the Binet A and the Binet B + C groups. Although hemostatic alterations may occur in patients with CLL, these parameters do not seem to be useful to indicate disease progression.Resumo em Inglês:
Abstract Osteoporosis is a chronic disease of bone that increases risk of low-trauma fracture. Chronic treatment may lead to lower adherence with medication. The current study aims are to determine adherence rate of antiosteoporotic medication by Medication Possession Ratio. Data has been collected from outpatient settings registering cases of postmenopausal osteoporotic women taking medications for an average duration of one year in Karachi. These patients were classified in lower, middle, and affluent socioeconomic classes. Collected data were analyzed by the standardized formula of Medication Possession Ratio and SPSS. Average Medication Possession Ratio ≥80% achieved by Risedronate Brands in the middle class (80.28%±4.41), the affluent class (82.50%±5.09), Raloxifen Brands in affluent class (93.62%±1.57), Gonadotropics in the middle class (81.36%±6.02), affluent class (91.09%±2.05), Alendronate Brands in affluent class (85.42%±5.46). Average Medication Possession Ratio is <80% with all antiosteoporotic medication in the lower class, while the average Medication Possession Ratio of Calcium and Vitamin D is ≥80% in all groups except lower class. Adherence rate was significantly higher among Alendronate group compare to Risedronate (p=0.044). Medication Possession Ratio is greater than 80% among all classes of low-cost antiosteoporotic medications. In addition, patients on once weekly oral medications are more adherent and compliant compare to oral daily or intranasal medications.Resumo em Inglês:
Abstract Various pharmacological effects including anti-inflammatory and anti-oxidant properties were shown for woody endocarpium of walnut alcoholic extract (WEW). In the study, the effect of the WEW extract in acetic acid induced ulcerative colitis in rats was evaluated. Thiol, glutathione peroxidase (GPX), malondialdehyde (MDA), superoxide dismutase (SOD) and gastric acid levels and pathological changes in the colon were investigated in the control group (C), ulcerative colitis group (UC), UC groups treated with WEW extract (10, 20, and 50 mg/kg) and sulfasalazine. Levels of gastric acid, MDA and pathological scores in colon were increased but SOD, GPX and thiol levels were decreased in UC animals compared to those of the control group (p<0.001). Treatment with the highest concentration of extract significantly improved level of thiol and pathological scores compared to the UC group (p<0.05 to p<0.001). Treatment with the two higher concentrations of extract also significantly decreased acid level compared to the UC group (p<0.01 to p<0.001). There was significant improvement in MDA due to treatment with the all concentrations of the extract (p<0.001). Sulfasalazine treatment also significantly improved most parameters compared to the UC group but did not changed pathological scores (p<0.05 to p<0.001). These results indicated a possible preventive therapeutic effect for the WEW extract on UC.Resumo em Inglês:
Abstract In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound.Resumo em Inglês:
Abstract The first report about antimicrobial resistance was published in the 1940s. And today, the antimicrobial resistance has become a worldwide problem. Because of this problem, there is a need to develop new drugs. That’s why we synthesized some novel thiazolidine-4-one derivatives and evaluated their antimicrobial activity. The final compounds were obtained by reacting 2-[(4,5-diphenylthiazol-2-yl)imino]thiazolidin-4-one with some aryl aldehydes. The synthesized compounds were investigated for their antimicrobial activity against four Candida species, five gram-negative and four gram-positive bacterial species. The lead compounds (4a- h) were obtained with a yield of at least 70%. All compounds showed antimicrobial activity. Compound 4f (MIC: 31.25 µg/ml) exhibited more efficacy than the other compounds against C. glabrata (ATCC 24433). Compound 4b (MIC: 62.5 µg/ml) was the most active compound against all bacterial species, particularly K. pneumoniae (NCTC 9633). Whereas, compound 4c (MIC: <31.25 µg/ml) was observed as the most active compound against E. coli (ATCC 25922). In general, all compounds (4a-4h) showed antimicrobial activity against all fungi and bacterial species. Compounds 4b (2,6-dichlorobenzylidene), 4c (2,6-dihydroxybenzylidene), 4f (1H-pyrrol-2- yl)methylene), 4g (4-triflouromethylbenzylidene) and 4h (2,3,4-trimethoxybenzylidene) were determined as the most active compounds.Resumo em Inglês:
Abstract Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.Resumo em Inglês:
Abstract The main purposes of the current study were to formulate o/w nanoemulsions as a carrier for Tamarindus indica (tamarind) fruit pulp extract and to study the antioxidant and antibacterial potentials of nanoemulsions containing tamarind extract, focusing on cosmetic/hygiene applications. The o/w nanoemulsions using a mixture of Tween 80 and Span 80 as an emulsifier (5%w/w) were prepared by a high pressure homogenization process. Two concentrations of sweet tamarind extract, 3.3 and 6.6%w/w, based on the bioactivity study, were incorporated into the blank nanoemulsions to produce loaded nanoemulsions, F1-3.3TE (3.3%) and F1- 6.6TE (6.6%). As compared with the unloaded nanoemulsion, both tamarind extract loaded nanoemulsions showed reduced pH and significantly increased viscosity. Overall, the loaded nanoemulsions had droplet sizes of approximately 130 nm, zeta potential around -38 mV and polydispersity index (PDI) values less than 0.2. The nanoemulsion F1-3.3TE had better stability (e.g. significantly greater % tartaric acid content and lesser PDI value) than the nanoemulsion F1-6.6TE did. The antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay revealed that the nanoemulsions F1-3.3TE and F1-6.6TE had scavenging activities of 81.66 ± 0.77% and 63.80 ± 0.79%, respectively. However, antioxidant activity of these two formulations decreased under stress conditions (heating-cooling cycles). Such incidence did not occur for their antibacterial properties investigated by agar well diffusion technique. The two formulations exhibited inhibition zones of approximately 24.0-27.7 mm against Staphylococcus aureus and Staphylococcus epidermidis, responsible for malodor of underarms. The results suggest the potential of using sweet tamarind pulp extract loaded nanoemulsions as hygiene products.Resumo em Inglês:
Abstract Diethylcarbamazine-loaded nanoparticles were previously evaluated for their anti-inflammatory activity. However, little is known regarding their physicochemical properties. Thus, the purpose of this study was to physiochemically characterize diethylcarbamazine-loaded poly(caprolactone) nanoparticles and evaluate their in vitro cytotoxicity. All formulations were prepared using the double-emulsion method. The average particle size was in the ranged between 298 and 364 nm and the polydispersity indexes were below 0.3. The zeta potential values were marginally negative, which may be related to drug loading, as higher loading led to an increase in the modulus of the zeta potential values. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) analysis did not reveal any chemical interactions between the chemicals used and the absence of drug in crystalline form on the nanoparticle surfaces. The in vitro drug release study revealed a concentration-dependent release from the nanoparticles into the medium. The in vitro cytotoxicity assay demonstrated the biocompatibility of the blank and loaded nanoparticles. Hence, all formulations presented good physicochemical and safety properties, corroborating the in vivo anti-inflammatory activity, previously reported by our group.Resumo em Inglês:
Abstract Chronic type 2 diabetes mellitus (T2DM) and its associated diseases are major concern among human population and also responsible for significant mortality rate. Hence, the present study aims to evaluate and correlate the invertase inhibition, antioxidant activity and control against DFU causing bacterial pathogens by Pandanus odoratissimus flowers. Two dimensional preparative thin layer chromatography (2D PTLC) was adopted to purify the phenolic acid component and LC-MS2 was done to predict the phenolic acid structures. Standard spectrophotometry methods were adopted to investigate the in vitro invertase inhibitory and antioxidant (CUPRAC and ABTS) activities. Agar well diffusion and broth dilution assays were used to record the antibacterial property against DFU causing pathogens isolated from clinical samples. Statistical analyses were used to validate the experiments. A new and novel diferuloyl glycerate related phenolic acid (m/z 442) purified from PTLC eluate has recorded satisfactory cupric ion reducing power (ED50= 441.4±2.5 µg), moderate ABTS radical scavenging activity (IC50= 450.3±10 µg; 32.5±1.5%), and a near moderate, in vitro, invertase mixed type inhibition (24.5±4.5%; Ki: 400 µg). Similarly, bacterial growth inhibitory kinetics has showed a significant inhibition against E. coli and S. aureus.Resumo em Inglês:
Abstract The aim of this paper is to study the chemical composition of alkaloids present in Haloxylon scoparium Pomel extracts and to evaluate their antioxidant capacity. The alkaloids were isolated from two parts of Haloxylon scoparium plant by two extraction protocols. and The quantitative study made it possible to propose the best protocol for the extraction of the alkaloids. Moreover, GC-MS analysis of alkaloid extracts allowed us to determine their chemical composition. Haloxylon scoparium contains four types of alkaloids: tetraisoquinolines, phenylethylamines, tryptolines and tryptamines. The main compounds are the tetraisoquinolines type, the predominant product of which was N-methylsalsoline. These compounds present a great interest for the researchers due to their various pharmacological and biological activities. The antioxidant effect of the different plant extracts was studied by two methods: the ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl hydrazyl free radical (DPPH·) scavenging tests. The results show that extracts of root part are more active than those from aerial part; the acetone/water extract is the most powerful. The interesting results obtained in this study will be supplemented by other analyses and biological tests in order to better valorize this plant.Resumo em Inglês:
Abstract The pursuit of quality of life, which has become marked in recent years, has translated into important population health benefits. This study assessed the quality of life of patients with type 2 diabetes (T2DM) who received pharmaceutical care, and their satisfaction with the service provided in community pharmacies. This single blind, randomized controlled clinical trial included 100 patients. The intervention group (N=47) received pharmaceutical care by a clinical pharmacist and the control group (N=42) received standard care. The Quality of Life Diabetes Questionnaire (DQOL) was used to measure all participants´ quality of life at study enrollment and six months later. Satisfaction of the participants in the intervention group was measured using a validated 14-items questionnaire. At the end of the study, participants in the intervention group had a statistically significant improvement in DQOL scores ( -0.62 x 1.57, p < 0.001) and were highly satisfied with the intervention (96% excellent satisfaction scores). Pharmaceutical care practice was associated with high satisfaction and increased quality of life scores in T2DM patients. These results underscore the important role of pharmacists to improve the health of diabetic patients.Resumo em Inglês:
Abstract Nordihydroguaiaretic acid (NDGA) is a natural product obtained by the alkaline extraction of dried plants of Larrea tridentata species. Due to the biological properties presented, such as antioxidant, anti-inflammatory, antiviral and cytotoxic capacity, this compound is being increasingly studied. In this review, it was evaluated the benefits of NDGA against different animal models. Besides that, it was found that this compound has antitumor activity similar to its synthetic derivative terameprocol in prostate tumors. The hypoglycemic effect may be evidenced by the inhibition of sugar uptake by NDGA; in obesity, studies have observed that NDGA presented a positive regulatory effect for Peroxisome proliferator-activated receptors (PPAR-α) involved in the oxidation of hepatic fatty acids and reduced the expression of lipogenic genes. Regarding its antioxidant potential, its mechanism is related to the ability to in vitro scavenging reactive substances. Although there are several studies demonstrating the benefits of using NDGA, there are also reports of its toxicity, mainly of liver damage and nephrotoxicity.Resumo em Inglês:
Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.Resumo em Inglês:
Abstract The main aim of the study is to quantify the cytotoxic property of the Fucoidan extracted from the Turbinaria conoides using the MTT assay with the standard fucose. Fucoidan was extracted using the soaked water method and it was determined using the HPLC procedure the obtained Test sample Fucoidan extracted from the Turbinaria conoides and standard fucose was subjected to the cytotoxicity assay against the MCF7 Human breast cancer cell line, A549 lung cancer cell line, and L929 normal mouse fibroblast cell line. From the results it was found that the Test sample showed good IC50 value for MCF7 cell line then A549 with an increasing concentration 24 hours incubation at 37°C The IC50 for MCF7 was 115.21 µg/ml and A549 396.46µg/ml and the Fucoidan extract was checked for its cytotoxicity against the normal mouse fibroblast cell line L929, Fucoidan was found non-lethal to the L929 mouse fibroblast normal cell line. Standard fucose also gave a significant result towards MCF7 and against the L929. This indicates that the Fucoidan extracted from Tubinaria conoides shows better anticancer potential in it. Hence its application can be further extended in the pharmacological fields.Resumo em Inglês:
Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.Resumo em Inglês:
Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.Resumo em Inglês:
Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats.Resumo em Inglês:
Abstract The aim of our study was to assess risk factors for potential drug-drug interactions (pDDIs) of statins across different phases of treatment of acute coronary syndrome (ACS) patients: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase) and at discharge from hospital (third phase). This was a post hoc analysis of the data collected during the retrospective observational cohort study conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, Serbia. Patients prescribed statins were identified from the original study population: 156, 240 and 236 patients for the first, second and third phases, respectively. At least one statin pDDI was present in 113 (72.4%), 161 (67.1%) and 139 (58.9%) patients in the first, second and third phases, respectively. Heart failure, arrhythmias after ACS, CRP, triglycerides, length of hospitalization, number of prescribed drugs, antiarrhythmic drugs, and clopidogrel seem to increase the risk of statin pDDIs in at least one treatment phase. Physicians should be vigilant to the possibility of statin pDDIs in ACS patients who have factors that may increase their rate.Resumo em Inglês:
Abstract This work aims to ascertain the comprehensiveness of dissolution tests for oral suspensions registered in Brazil and the USA. After consulting literature since 1994, a paucity of information about dissolution methods for suspensions was detected. It makes it difficult to establish the most appropriate test parameters. In January, 2019, there were 46 drugs registered in Anvisa (Brazil) as oral suspension, being 47 reference, 173 generic and 114 interchangeable similar (IS) medicines; while in the USA, 90 drugs were registered as oral suspension by FDA, 235 Abreviatted New Drug Application and 111 New Drug Application medicines. Out of 46 and 90, only six and 15 drugs as oral suspension had a pharmacopeial dissolution test, corresponding to 70 (20.9%) and 82 (23.7%) products in Brazil and the USA, respectively. Dissolution studies were found for 17 drugs as oral suspension in the non-compendial literature. Dissolution test conditions were established to few marketable oral suspension drugs, most of which are BCS class II or IV. Thus, investing in dissolution studies could subsidize the registration of these products by regulators, especially for generic and IS drugs, by comparing dissolution profiles, and predicting their in vivo behavior to avoid exposure of healthy individuals to clinical research.Resumo em Inglês:
Abstract Bioequivalence (BE) assessment of topical drug products is a long-standing challenge. Agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published several drafts in recent years suggesting different approaches as alternative to evaluate the BE. A proposed Topical Classification System (TCS) has even been discussed. Given the above, the objective of this research was to use in vitro and in vivo BE approaches to evaluate Brazilian marketed mupirocin (MPC) ointments, previously classified as TCS class The in vitro permeation test (IVPT) was performed by applying formulations to pig skin by Franz cells. The in vivo methodology was dermatopharmacokinetic (DPK). These approaches (in vivo tape stripping and IVPT) demonstrated capability of distinguishing among different formulations, thus making them useful methodologies for BE evaluation.Resumo em Inglês:
Abstract The aim of the current study was to determine the chemical constituents of essential oil and to study the antibacterial and antioxidant activities of essential oil and the extracts obtained from the raw material of Ziziphora wild growing in the floras of Armenia and Artsakh cultivated in the hydroponic conditions. The essential oils were obtained by the method of hydro-distillation. The determination of the essential oil constituents were performed by the GC-MS method. Agar disk diffusion method was used to study the antimicrobial activity of essential oils. The antioxidant activity determination was carried out DPPH test by the spectrophotometric method, at the same time IC50 was determined. The highest values of the essential oils yield (1.25 ± 0.01%) and IC50 13.83±0.218(x10-5)g/l) were received for the plant cultivated in hydroponic conditions. For the first time in the above studied samples, by the method of GC-MS more than 70 components were revealed. The results of the study showed that essential oils of Ziziphora exhibit antimicrobial activity and the extracts revealed relatively expressed antioxidant activity. The study results show the future prospects of the use of Ziziphora not only as the source of flavonoids and essential oils, but also antimicrobial and antioxidant agents.Resumo em Inglês:
Abstract Silver nanoparticles (AgNPs) are among the most known nanomaterials being used for several purposes, including medical applications. In this study, Calendula officinalis L. flower extract and silver nitrate were used for green synthesis of silver nanoparticles under red, green and blue light-emitting diodes. AgNPs were characterized by Ultraviolet-Visible Spectrophotometry, Field Emission Scanning Electron Microscopy, Dynamic Light Scattering, Electrophoretic Mobility, Fourier Transform Infrared Spectroscopy and X-ray Diffraction. Isotropic and anisotropic silver nanoparticles were obtained, presenting hydrodinamic diameters ranging 90 - 180 nm, polydispersity (PdI > 0.2) and moderate stability (zeta potential values around - 20 mV).Resumo em Inglês:
Abstract To evaluate the effectiveness of an anticoagulation protocol adapted in a mobile application (appG) for patients using warfarin. This was a cluster randomized controlled clinical trial carried out in basic health centers of Ijui, RS, Brazil, between April and October 2017. The appG was installed on the cell phones of all physicians belonging to the intervention group. Primary outcomes were bleeding and thrombosis, and secondary outcomes were changes in the dose of warfarin, use of new drugs, drug interactions, search for health services, and remaining on the target international normalized ratio. Thirty-three patients belonging to 11 basic health centers were included in this study. From these, 15 patients were in the intervention group which used the appG, and 18 were in the control group. After 6 months, patients in the appG group had fewer bleeding events (7% versus 50%, p-value=0.028) and a lower weekly dose of warfarin (29.3 ± 9.7 mg versus 41.7 ± 12.5 mg, p-value=0.030) when compared to the control group. The anticoagulation protocol adapted in a mobile app reduced bleeding in patients using warfarin.Resumo em Inglês:
Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it’s protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.Resumo em Inglês:
Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.Resumo em Inglês:
Abstract The illicit market of counterfeit medicines containing sildenafil and tadalafil has been causing serious public health problems. Thus, further studies on this illicit association are needed. A stability-indicating HPLC method was developed for simultaneous determination of tadalafil (TAD) and sildenafil (SIL) using a C18 column (250 x 4.6 mm, 5 µm). Detection was achieved at 284 nm, for TAD, and 292 nm, for SIL. The method was considered to be specific, linear, precise, accurate, robust, and sensitive. In the photodegradation kinetic studies, the drugs showed a first-order reaction rate when isolated, and zero-order when associated. Toxicological assays demonstrated that the photodegraded drugs decreased cell viability in compared to non- degraded drugs, suggesting cytotoxic activity. Additional, mutagenic activity was not observed under the tested conditions. Photodegraded drugs, in association, depicted DNA damage index, suggesting genotoxic effects. The obtained results will be able to support the forensic intelligence laboratories, as well as to alert the population about the risk inherent to consuming counterfeit products.Resumo em Inglês:
Abstract This study reviews the knowledge on the use of conventional dental whitening and the use of enzymes as a new approach in bleaching. A review of the literature was based on academic articles and on patents related to the use of enzymes in dental bleaching. Tooth whitening techniques used nowadays are well reported in the literature, and its mechanism of action consists of an oxidoreduction reaction with the release of free radicals. The great instability of radicals, when in contact with the tissues, promotes oxidation and reduction in the size of the pigment chains incorporated into them. These pigments are eventually broken down into smaller and smaller molecular chains and end up being diffused from the dental structure. In turn, the use of enzymes aimed at tooth whitening can be a less harmful alternative to the tooth because their specificity regarding the substrate makes them of great interest to perform specific reactions, reducing collateral effects. The use of proteolytic enzymes and oxidoreductases paired with the application of peroxides, can be a promising alternative for obtaining even better results in the dental bleaching process.Resumo em Inglês:
Abstract The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as “add- on” therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin.Resumo em Inglês:
Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson’s Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.Resumo em Inglês:
Abstract The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria.Resumo em Inglês:
Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.Resumo em Inglês:
Abstract The Disease Activity Score 28 (DAS28) shows discrepancies when using erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) scores to assess rheumatoid arthritis (RA). This study aimed to verify the agreement between the DAS28-CRP and DAS28-ESR scores in patients with RA from the south of Brazil. A unicentric cross-sectional study was performed (n = 56). The diagnosis of the patients followed the American College of Rheumatology/ European League Against Rheumatism criteria, and their DAS28 were calculated. The DAS28- ESR score was higher than the DAS28-CRP (DAS28-ESR mean 4.8±1.6; DAS28-CRP mean 4.3±1.4) for 83.9% of the patients. The DAS28-CRP and DAS28-ESR scores showed a very strong correlation (Pearson’s coefficient = 0.922; P<0.0001, 95% CI +0.87 to +0.95, statistical power 100%). Spearman’s correlation coefficient (0.49; P=0.0001, 95% CI +0.25 to +0.67, statistical power 47.54%) showed a moderate correlation between the unique components of the DAS28 formulas. There was agreement between the tests in only 36 of the patients (64.29%). Among the discordant categories, DAS28-ESR overestimated the classification in 16 patients (28.5%). The Kappa coefficient between the categories was 0.465 (SE 0.084, 95% CI +0.301 to +0.630), showing a moderate degree of agreement between the instruments. Although the DAS28-ESR and DAS28-CRP were highly correlated, they differed significantly in terms of patient categorization and should not be used interchangeably.Resumo em Inglês:
Abstract We report a case of Mycobacterium abscessus subsp. bolletii colonization in upper respiratory tract of an immunocompetent patient, who was misdiagnosed as tuberculosis by Acid Fast Bacilli (AFB) and cord factor formation observed directly from the sputa culture in liquid medium. This fact reflected a significant impact on the individual case’s life and showed the importance to identify the mycobacteria isolated from clinical sample at species level, and to determine the true implication of nontuberculous mycobacteria (NTM) detected in clinical samples.Resumo em Inglês:
Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.Resumo em Inglês:
Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 μg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds.Resumo em Inglês:
Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the “Interchangeable Pharmaceutical Product in the Treatment of Epilepsies” questionnaire was applied. The questionnaires “Adverse Events Profile” and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event “problems with skin” incresead (p=0.023) and “upset stomach” decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: “energy/fatigue” (p=0.048) and “total score” (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients’ perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients’ life.Resumo em Inglês:
Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff’s apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.Resumo em Inglês:
Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl’s staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders.Resumo em Inglês:
Abstract This work aims to develop analytical methods using high-performance liquid chromatography with a diode array detector (HPLC-DAD) for analysis and quantification of avermectins (AVMs) and milbemycins (MBMs) in bulk samples. First, the methods were optimized and some parameters such as temperature, flow rate, injection volume and mobile phase with different proportions of solvents were evaluated. The best chromatographic conditions were obtained using the Phenomenex® C18 (150 × 4.60 mm, 5 μm) column at a temperature of 20 °C, flow rate of 1.2 mL min-1, injection volume of 20 μL, and detection at 250 nm. Acetonitrile: ultrapure water (87: 13, v/v) was used as mobile phase for moxidectin and eprinomectin, and acetonitrile: methanol: ultrapure water (53: 35: 12, v/v/v) for abamectin and ivermectin. Under these conditions satisfactory results were obtained, with appropriate limits of detection and quantification, acceptable linearity, precision, accuracy, and robustness. These methods satisfy the need for analytical methods for the multi-determination of MBMs and the B1a and B1b forms of AVMs by HPLC-DAD, which can be considered simple, effective, innovative and should aid in the development of the field.Resumo em Inglês:
Abstract Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.Resumo em Inglês:
Abstract Highly Active Antiretroviral therapy (HAART) depends on optimal adherence to be effective. Pharmacotherapeutic follow-up can be used as a strategy for treatment fidelity. To provide pharmaceutical care for HAART patients, to assess adherence, to identify and resolve drug related problems (DRP). This is a prospective, interventional study aimed at people on HAART. Data was collected using the pharmacotherapeutic follow-up form and CEAT-VIH. There was a predominance of women (59%), older than 33 years (75%), mostly single (43%). Regarding adherence, 64% had insufficient adherence at the start of the study, while 36% had strict/adequate adherence. After the pharmacotherapeutic follow-up, 70% presented strict/adequate adherence. Regarding HAART, the relationship between adhesion versus time of HAART and adherence versus regimen used was significant, considering that less time of therapy and regimen containing protease inhibitors are predictors for insufficient adherence. Regarding the DRP identified (f=77), missed pills (32%), untreated disease, incorrect management frequency, and undue self-medication (12%) were the most frequent. Pharmaceutical interventions (f=137) were predominantly advising related to specific pharmacological treatment (32%), non-pharmacological measures (20%), and medication suspension (9%). Pharmaceutical care was shown to be animportant strategy, within the multi professional team, to improve adherence, besides identifying and resolving DRP.Resumo em Inglês:
Abstract We analyzed use of medication and associated factors in adults aged 18-59 years living in Rio Branco, Acre. This is a cross-sectional and population-based study that used a probabilistic sample of the population from rural and urban areas of the city of Rio Branco, Acre. The Prevalence Ratio (PR) was calculated with 95% confidence intervals and associations were estimated by Poisson regression. This study found a 29.4% prevalence ratio of use of medication among individuals aged from 18 to 59 years (685 adults: 473 women and 212 men; producing estimates for 211,902 adults: 110,769 women and 101,133 men). After adjusted analysis, their use was associated with: age (50-59 years, PR: 2.36; 95%CI: 2.29-2.43); women (PR: 1.25; 95%CI: 1.23-1.27); up to elementary school (PR: 1.13; 95%CI: 1.11-1.15); and poor or very poor self-rated health (PR: 1.47; 95%CI: 1.43-1.51). The health conditions associated with use of medication were: number of comorbidities, hypertension, diabetes, insomnia, depression, number of health complaints and use of health services. The most frequently used drugs were those belonging to the following ATC categories: alimentary tract and metabolism, cardiovascular system, nervous system, and the musculoskeletal system.Resumo em Inglês:
Abstract Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.Resumo em Inglês:
Abstract Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression.Resumo em Inglês:
Abstract The development of stable cell lines producing recombinant proteins is very time-consuming and laborious. One of the practical approaches successfully performed is Fluorescence-Activated Cell Sorting (FACS). A mutated chimeric tissue plasminogen activator (mt-PA) was developed by removing the first three domains of t-PA, insertion of GHRP sequence and mutation toward resistance to plasminogen activator inhibitor-1 (PAI-1). In the current study, a new stable CHO-DG44 cell line producing mt-PA was developed by two sequential clonal selections: FACS and clonal-selection by limiting dilution. Furthermore, the expression was more evaluated using two different expression media. Finally, the high-producing clones were selected based on the dot blot and amidolytic activity test. The transfection efficiency of CHO-DG44 cells was 38% as measured by flow cytometry on green fluorescent protein (GFP). After performing FACS on stable cell pools, the expression yield was increased to fifty-fold. In terms of growth profile, CD-DG44 showed higher viability and cell density results than ProCHO5 medium. The expression of mt-PA was significantly higher in CD-DG44 than in ProCHO5, 765 and 280 IU/mL, respectively. Our data indicated that selection of an appropriate expression medium played a critical role in the development of potent producing stable cells by FACS.Resumo em Inglês:
Abstract Due to the fact that different isoforms of carbonic anhydrase play distinct physiological roles, their diseases/disorders involvement are different as well. Involvement in major disorders such as glaucoma, epilepsy, Alzheimer’s disease, obesity and cancers, have turned carbonic anhydrase into a popular case study in the field of rational drug design. Since carbonic anhydrases are highly similar with regard to their structures, selective inhibition of different isoforms has been a significant challenge. By applying a proteochemometrics approach, herein the chemical interaction space governed by acyl selenoureido benzensulfonamides and human carbonic anhydrases is explored. To assess the validity, robustness and predictivity power of the proteochemometrics model, a diverse set of validation methods was used. The final model is shown to provide valuable structural information that can be considered for new selective inhibitors design. Using the supplied information and to show the applicability of the constructed model, new compounds were designed. Monitoring of selectivity ratios of new designs shows very promising results with regard to their selectivity for a specific isoform of carbonic anhydrase.Resumo em Inglês:
Abstract Innovation is the driving force that is able to create and transform products, processes, and organization in the health system. Innovation in the field of pharmaceutical assistance covers a wide spectrum of aspects, from drug discovery to pharmaceutical care, contributing to the improvement in treatments through novel drugs or methods. This work will present the major characteristics of innovation with special emphasis on aspects pertaining to pharmaceutical assistance. The types and models of innovation, as well as the interaction between academia and industry, will be presented with examples of successful products and methods. In addition, the challenges and perspectives for innovation in pharmaceutical assistance will be discussed with a focus on drug discovery.Resumo em Inglês:
Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.Resumo em Inglês:
Abstract The purpose of this study is to estimate the prevalence of and characterize the use of psychoactive drugs among drug users in a Brazilian municipality, relating the findings to factors associated with the consumption of these substances. Through a cross-sectional design, 1,355 drug users from the public health systems community pharmacies were interviewed. Sociodemographic and health-related data were collected, as well as any other prescribed drugs. The prevalence of psychoactive drug use within the last month was 31.0%, with antidepressants and benzodiazepines being the most prescribed (53.5% and 24.6% respectively). Most psychoactive drug users were female (81.9%), lived with a partner (52.6%), had private health insurance (69.2%) and a monthly per-capita income up to one minimum wage (54.0%). The adjusted Odds Ratio (OR) confirmed the following factors to be positively associated with the use of psychoactive drugs: female gender (OR=2.06; 95% CI 1.44; 2.95), age ≥60 years old (OR=1.77; 95% CI 1.26; 2.48), follow-up with a psychologist (OR=4.12; 95% CI 1.84; 5.25), absence of regular physical activity (OR=1.59; 95% CI 1.13; 2.23), and smokers (OR=1.94; 95% CI 1.26; 2.97). Approximately one out of three individuals used at least one psychoactive drug. Health managers should focus the planning and actions aimed at their rational use for these groups, leading to increased overall treatment success.Resumo em Inglês:
Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.Resumo em Inglês:
Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and β4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and β4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and β4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes’ α5 and β4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes’ α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed β4. Psoriatic keratinocytes’ α5 was increased by IL-13/17A, decreased by IFN-γ; but β4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and β4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently.Resumo em Inglês:
Abstract Dissolution is a key step in the uptake of oral drugs. In order to compare the behaviour of the dissolution of two formulations, the dissolution profile test was used. This assay must be discriminative and should mimic in vivo conditions. Many dissolution media described in pharmacopoeias are not predictive of bioavailability. Due to this, biorelevant media are used as an alternative to solve this problem. The objective of this work is to evaluate the relevance of biorelevant dissolution media to predict in vivo drug dissolution. For this, a bibliographic search was carried out in scientific databases. The search was first performed for articles verifying the physicochemical properties of human gastrointestinal fluids. Subsequently, a comparison was made between the properties of gastrointestinal fluids and those of biorelevant and pharmacopoeial media. Finally, the results of bioequivalence studies and dissolution profile tests in biorelevant media described in the literature were compared. The results revealed that there are a few publications that have analysed some physicochemical properties of gastrointestinal fluids. In addition, high variability was observed for some properties. Regarding the comparison of these properties with pharmacopoeial media and biorelevant media, the analysis showed that the biorelevant media are more similar to gastrointestinal fluids than the pharmacopoeial media. Finally, the in vitro dissolution profile results were similar to the results obtained in vivo. Thus, biorelevant media may be useful for analysing dissolution profiles.Resumo em Inglês:
Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.Resumo em Inglês:
Abstract In China, Scutellaria is used for treating inflammatory-related diseases. Baicalin is the main active component of Scutellaria and has protective effects on acute pancreatitis. However, the mechanism of Baicalin is still unclear. In this study, the protective effects of baicalin on acute pancreatitis induced by taurocholate and its mechanism are investigated. In this study, mice were randomly divided into three groups: sham operation, model, and treatment groups. Acute pancreatitis in mice was induced by intraperitoneal injection of taurocholate (35 mg/kg). The treatment group was given baicalin (100 mg/kg) 2 h before acute pancreatitis induction. The mRNA expression levels of miR-429, nuclear factor kappa B65(NF-kB65), toll-like receptor 4(TLR4), TNF receptor associated factor6 (TRAF6), NF-kappa-B inhibitor(IkB), Follistatin-like 1 (FSTL1), and interleukin-1 receptor-associated kinase (IRAK) in the liver tissues 24 h after intraperitoneal injection were detected by RT-PCR. Then, the expression levels of NF-kB65, p-NF-κB65, TLR4, TRAF6, IkB, FSTL1, IRAK, p- IRAK, and p- IkB-а proteins were detected by Western blot. IL-6, TNF-α and IL-1 β in plasma were measured by ELISA, and histopathological changes in the pancreases of the mice were observed. The results showed that after baicalin treatment, miR-429 expression in the pancreatic tissues and the expression levels of NF-kB65, TLR4, TRAF6, p-IkB-а, FSTL1, and p-IRAK decreased. Similarly, pancreatic myeloperoxidase (MPO) activity and the plasma levels of IL-6, TNF-а, IL-12, IL-1β1, endotoxin, serum amylase, and lipase were reduced. Thus, the pancreatic injury induced by taurocholate was alleviated. The present study indicates that pretreatment with Baicalin can alleviate acute pancreatic injury induced by taurocholate in mice. The mechanism may be associated with the decreased miR-429 expression, reduced FSTL1 signaling pathway activity, TLR4 and TLR4/MyD88 signaling pathway inhibition, and reduced pancreatic inflammation. FSTL1 is the regulatory target for miR-429.Resumo em Inglês:
Abstract Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of Anethum graveolens, Citrus aurantium, Cynara scolymus, Portulaca oleracea, and Silybum marianum (2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD.Resumo em Inglês:
Abstract The objective of this study is to examine the antidepressant and antioxidant effects of thymoquinone (TQ) on reserpine-induced depression, and to investigate the antidepressant and antioxidant activity of combined treatment of TQ+citalopram. In total, 36 male Wistar rats were randomly divided into 6 groups: 1)control1, 2)control2, 3)reserpine, 4)reserpine+TQ 5)reserpine+citalopram and 6)reserpine+TQ+citalopram. Depression was induced by administering intraperitoneal reserpine of 0.2mg/kg/14days. For antidepressant effects, 10 mg/kg TQ and/or 10 mg/kg citalopram was administered intragastrically 30 minutes prior to the administration of reserpine. Rat behavior was examined using the Behavioral Test following the completion of treatment protocol. Total nitric oxide (NOx) levels, malondialdehyde (MDA) levels, total oxidants status (TOS), total antioxidant status (TAS) in brain cortex, plasma as well as brain cortex glutathione (GSH) and levels of plasma total sulfhydryl groups (RSH) were examined. Treatment with TQ ameliorated the reserpine-induced changes in the Behavioral Test (p<0.05). TQ treatment significantly increased dopamine (DA) and noradrenaline (NA) expressions when compared to the R group (p<0.01). Serotonin (5-HT) expression also increased significantly (p<0.05). Brain cortex and plasma TOS, MDA and NOx levels decreased, whereas TAS, GSH and RSH levels increased (p< 0.05). TQ has the ability to prevent depression induced by reserpine. The combination of TQ+citalopram can be used in the treatment of depression with a stronger antioxidant effectResumo em Inglês:
Abstract TCMSP platform of systematic pharmacology of traditional Chinese medicine This study aimed to investigate the molecular mechanism of Fructus Ligustri Lucidi (NZZ, Chinese abbreviation) against osteoporosis (OP) by means of network pharmacology.ChemDraw Professional 15.1 software and Molinspiration Smiles database were used to draw the chemical formulas of the components. The active ingredients and related target proteins of NZZ were searched in platform of systematic pharmacology of traditional Chinese medicine database, Drugbank, Therapeutic Target Database, SymMap and other databases. Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the selected target through Enrichr and KEGG Automatic Annotation databases, and their mechanism was studied. A total of 29 compounds and 140 corresponding targets, including 14 key targets and 14 protein factors in protein-protein interaction core network were obtained. The key targets were tumor necrosis factor(TNF), interleukin(IL)-6R and sestrogen receptor alpha. The number of GO items was 466 (P<0.05), including 399 items of biological process (BP), 54 items of cell composition (MF) and 13 items of molecular function (CC). KEGG pathway enrichment screened 85 signaling pathways (P<0.05), including the IL-17 signaling pathway, TNF signaling pathway, advanced glycation end products and their receptors signaling pathway and cAMP signaling pathway. The active ingredients of NZZ. exert their anti-OP effects through multi-components, multi-targets and multi-pathways, which can provide new evidence for further study of their anti-OP mechanism.Resumo em Inglês:
Abstract To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière’s disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated.Resumo em Inglês:
Abstract Candida glabrata infections are responsible for deaths of people globally. Fluconazole is known to be less effective against C. glabrata, which developed many strategies to evade being destroyed by fluconazole. To achieve enhanced efficacy of fluconazole against C. glabrata, the interaction of fluconazole with sodium bicarbonate was investigated using the CLSI guidelines. The efficacy of fluconazole alone and in combination with sodium bicarbonate was evaluated using the time-kill and phospholipase production assays. Eventually, the expression of PLB was assessed using semi-quantitative RT-PCR to investigate the inhibitory properties of fluconazole alone and in combination with sodium bicarbonate against C. glabrata. The fluconazole/sodium bicarbonate combination displayed synergistic and antagonistic effects (FICI= 0.375-4.25). In C. glabrata ATCC, SN 152, and SN 164, the fluconazole/sodium bicarbonate combination exhibited a significant fungicidal activity (p< 0.05) but antagonistic effect in the case of SN 283. With exception of SN 283, a significant reduction was noted in phospholipase production in clinical isolates of C. glabrata treated with fluconazole/sodium bicarbonate combination. The PLB was down-regulated significantly by 0.168-0.515 fold in C. glabrata treated with fluconazole/sodium bicarbonate. The results suggested fluconazole/sodium bicarbonate to have a potential synergistic interaction in C. glabrata, and the underlying mechanism may be associated with phospholipase gene.Resumo em Inglês:
Abstract Flavonoids display various beneficial biological properties, such as antioxidant activity and low cytotoxicity, which make them useful ingredients in foods, pharmaceuticals, and functional cosmetics. In particular, dihydroquercetin (DHQ) is found in various forms, and its derivatives exhibit interesting biological properties. Herein, we report the synthesis of acetylated and butyrylated dihydroquercetin derivatives and their antimicrobial and antioxidant properties. The DHQ derivatives were identified using 1H and 13C NMR spectroscopies and high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. The chemical stabilities of the acetylated dihydroquercetin derivatives were found to depend on the number of acetate groups, with 3,3',4',4,7-pentaacetyldihydroquercetin found to be the most stable acetylated dihydroquercetin. Furthermore, 7,3',4'-triacetyl- dihydroquercetin exhibited potent antioxidant activity, with an IC50 of 56.67 ± 4.79 μg/mL in the 1,1-diphenyl-2-picrylhydrazyl assay, with DHQ exhibiting a value of 32.41 ± 3.35 μg/mL. The reactive-oxygen-species-scavenging activity of 7,3',4'-triacetyldihydroquercetin was highest among the esters in the ferric reducing ability of plasma assay, but lower than that of DHQ. Overall, both DHQ and 7,3',4'-triacetyldihydroquercetin exhibited antimicrobial behavior against S. aureus and P. acnes using the paper disc assay. DHQ displayed a higher antimicrobial activity, with minimum inhibitory concentrations of 625 μg/mL (P. acnes), 2,500 μg/mL (S. aureus), and 5,000 μg/mL (E. coli). DHQ and acetylated dihydroquercetins are potentially useful as complex antioxidant and antimicrobial materials.Resumo em Inglês:
Abstract To compare global endothelial function assessed by pulse wave analysis (PWA) using the ratio of endothelium dependent vasodilatation (EDV) to endothelium independent vasodilatation (EIV) in patients with hypercholesterolemia and controls. 92 subjects [46 hypercholesterolemics, 46 controls] were studied at standardized conditions. Baseline augmentation index (AIx) was assessed followed by the administration of 0.5 mg sublingual nitroglycerine, an endothelium independent vasodilator. AIx was assessed and the maximum change in AIx after nitroglycerine was recorded as EIV. After a washout period of 30 minutes, 400 µg of inhaled salbutamol, an endothelium dependent vasodilator was administered. AIx was assessed again and the maximum change in AIx after salbutamol was recorded as EDV. Global endothelial function was calculated as EDV:EIV ratio. EDV and EIV in patients with hypercholesterolemia compared to controls were 2.97 ± 3.95 and 6.65 ± 3.80 (p<0.001); and 13.41 ± 4.57 and 15.88 ± 4.78 (p=0.01) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls; 0.21 ± 0.38 and 0.44 ± 0.24 (p<0.001) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls. PWA is a potential clinical tool to assess global endothelial function in patients with hypercholesterolemia.Resumo em Inglês:
Abstract Xuezhikang (XZK) is an extract of Chinese red yeast rice. It has multiple protective effects in cardiovascular systems. However, the underlying mechanism by which XZK affects free fatty acid (FFA)-induced lipogenesis in hepatocellular steatosis model is still unknown. Herein, we investigated this mechanism in HepG2 cells. The HepG2 cells were treated with palmitate acid (PA) to induce lipogenesis. Then the PA-induced HepG2 cells were subsequently treated with XZK. After 24 h of treatment, we determined the intracellular triglyceride (TG) contents and average areas of lipid droplets. To study the involvement of AMPK signaling pathway, we pre-treated the PA-induced HepG2 cells with Compound C, an AMPK inhibitor, before XZK treatment. Expressions of p-AMPK and AMPK were determined by Western blot. The results showed that XZK decreased TG content and lipid accumulation in hepatocellular steatosis model. Compound C abolished the effects of XZK. These results demonstrated for the first time that XZK protects hepatocytes against lipid accumulation induced by free fatty acids. Its effects may be mediated by the activation of AMPK pathway.Resumo em Inglês:
Abstract Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich’s solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich’s ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways.Resumo em Inglês:
Abstract The objectives of this study were to describe work characteristics of Iraqi pharmacists, to compare pharmacist job satisfaction between private and public sectors and to assess factors influencing job satisfaction level. This cross-sectional study of pharmacists, their work sites and work satisfactions used an electronic questionnaire that was posted on Facebook pharmacy professional group from June to September 2018. The participants included pharmacists from all 18 Iraqi provinces. We used multiple linear regression to identify predictors of general job satisfaction among 13 pharmacist characteristics. We received 658 usable surveys. Approximately half (47.24%) of respondents indicated dissatisfaction with their primary workplace. Job performance, patient contact, satisfaction with manager, income and expectation satisfactions were significantly related with work satisfaction. Pharmacists working in the private sector had significantly more control over their workplace and higher satisfaction with manager, income and general satisfactions compared to those working in public sector. Pharmacists work in diverse settings across the public healthcare system, community pharmacies, private drug bureaus and academia. About half of them are dissatisfied with their primary workplace. The private sector has more satisfaction rate compared to the public sector. Thus, officials need to improve job environments in the public sector.Resumo em Inglês:
Abstract The present study evaluated 56 patients diagnosed with Chronic Lymphocytic Leukemia (CLL) and a control group of 44 clinically healthy subjects with no previous history of leukemia. Genetic expressions of AKT and microRNAs were evaluated by quantitative PCR (qPCR). A significant increase in AKT gene expression in patients when compared to controls was observed (p = 0.017). When the patients were stratified according to Binet subgroups, a significant difference was observed between the subgroups, with this protein kinase appearing more expressed in the B+C subgroup (p = 0.013). Regarding miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients, when compared to controls. However, no significant differences were observed in these microRNA expressions between the Binet subgroups (A versus B+C). By contrast, miR-21 to miR-27a oncogenes showed no expression difference between CLL patients and controls. AKT protein kinase is involved in the signaling cascade that occurs with BCR receptor activation, leading to increased lymphocyte survival and protection against the induction of cell death in CLL. Thus, increased AKT protein kinase expression and the reduction of miR-let-7b and miR-26a, both tumor suppressors, may explain increased lymphocyte survival in CLL patients and may be promising markers for the prognostic evaluation of this disease.Resumo em Inglês:
Abstract The β-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-β-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine.Resumo em Inglês:
Abstract Red lima bean (Phaseolus lunatus Linn) Family Fabaceae, has been modified by succinylation and annealing, and used as intra- and extra-granular disintegrants at concentrations of 5 and 10 %w/w in paracetamol tablet formulation in comparison with corn starch BP. The starches were characterised using FT-IR spectroscopy, SEM, proximate analysis, physicochemical and functional properties. FT-IR spectrometry revealed characteristic peaks at 1575.53 and 1713.99 cm-1 for the succinylated starch while the annealed showed no significant difference from the native starch. Modifications did not alter the ovoid shape of the native starch but reduced the particle size. Succinylation improved water absorption capacity, solubility and swelling of lima bean starch but annealing reduced the parameters. Tablets with disintegrants of lima bean starches generally had higher crushing strengths and lower friability than tablets with corn starch. Modifications reduced the disintegration time of the tablets when the starches were incorporated intra-granularly, which suggested particle-particle bond interruption and destruction of hydrogen bonds as mechanism of disintegration. Tablets containing 10 %w/w succinylated red lima bean starch incorporated intra-granularly had the highest disintegration efficiency ratio, DER, indicating a great balance between mechanical and disintegration properties. Modified red lima bean starches incorporated intra-granularly into paracetamol tablets led to faster disintegration and could efficiently substitute corn starch as disintegrant.Resumo em Inglês:
Abstract Proton pump inhibitors (PPI) are drugs that suppress gastric acid secretion. Its use, without support from scientific evidence, can contribute to polypharmacy, lead to drug interactions and, in the long term, cause serious adverse reactions. Studies advise physicians to deprescribe PPI. A quick review of scientific evidence, also called a rapid systematic review, on the deprescribing of PPI was performed. Evidence searches were performed in the LILACS, Embase, PubMed and NICE evidence databases with the terms “omeprazole”, “proton pump inhibitors”, “deprescription”, “deprescribing”. At LILACS these descriptors were also used in Portuguese and Spanish. Of 118 studies identified, four systematic reviews were selected for analysis. Abrupt deprescribing was associated with an increased risk of symptom recurrence. Fear of symptom recurrence is one of the major barriers to patient-related deprescribing. Educational interventions directed at prescribers, pharmacists, and patients are effective strategies in the deprescribing of PPI. Deprescribing process showed to be feasible in different contexts, with different strategies. The process is most effective through actions with educational and guidance materials directed to health professionals and patients, and with the involvement or leadership of the pharmacist.Resumo em Inglês:
Abstract In this present study, 63 different 5-[4-methyl-2-(pyridin-3/4-yl)thiazole-5-yl]-4-substituted-3-substituted benzylthio-4H-1,2,4-triazole derivatives were synthesized, and evaluated for their in vitro antimicrobial activity against various human pathogenic microorganisms and antioxidant activity. The derivatives were synthesized in a multi-step synthesis procedure including triazole and thiazole ring closure reactions, respectively. The synthesized derivatives (A1-24; B1-39) were screened for their antibacterial, antifungal, and antioxidant activities compared to standard agents. The derivatives possessing 3-pyridyl moiety particularly exhibited relatively high antibacterial activity (MIC= < 3.09-500 µg/mL) against Gram-positive bacteria, and compounds possessing 4-pyridyl moiety showed remarkable antioxidant activity.Resumo em Inglês:
Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.Resumo em Inglês:
Abstract Whole-body bone scintigraphy (WB-BS) is used for detecting and monitoring metastatic spread of prostate cancer (PCa) and to investigate bone pain episodes. To investigate the impact of a positive WB-BS on pain-relieving medicine prescription in PCa patients, a single-center, retrospective cohort study with PCa patients classified as positive for bone metastases (BM) by WB-BS was conducted. Demographic, clinical, and ambulatory pain-relieving medicine prescription data were evaluated. Pain-relieving medicines were categorized according to the WHO ‘Analgesic Ladder’. Regimens adopted before and after WB-BS were compared. Differences were considered significant at p<0.05. A total of 180 PCa patients were diagnosed with BM, 64.4% of whom were ≥65 years of age. Thirty-three patients were prescribed analgesics only after WB-BS, mostly including NSAIDs and weak opioids. Pain-relieving prescription changed after WB-BS in patients with prescriptions before and after WB-BS, with a reduction in NSAIDs and adjuvants and an increase in weak and strong opioids. In addition, 40% of patients with WHO analgesic step 1 drugs and 21.7% of patients with WHO step 2 drugs before WB-BS changed to other WHO steps after WB-BS. Pain-relieving prescriptions changed after a positive WB-BS, providing evidence that it could contribute to clinical management of painful metastatic PCa patients.Resumo em Inglês:
Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ’s effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.Resumo em Inglês:
Abstract Gabapentin is an antiepileptic drug prescribed for several neuropathic pain conditions. This study aimed to evaluate gabapentin (GAB) trough plasma concentration range and the applicability of therapeutic drug monitoring in patients with neuropathic pain. Fifty-three patients with neuropathic pain, aged 20 to 75, received gabapentin as treatment for at least 7 days. Gabapentin plasma concentration was sampled before GAB administration and quantified by liquid chromatography with a UV detector. GAB trough plasma concentration ranged between 0.40 and 11.94 µg/mL in patients with chronic neuropathic pain. No differences were observed in terms of GAB plasma concentrations between responsive and non-responsive patients. Our data suggest that the reference ranges suggested in the literature for patients with epilepsy should not be used for patients with neuropathic pain. Therapeutic drug monitoring of GAB was shown to be an important tool to assess treatment adherence.Resumo em Inglês:
Abstract In recent years, improvements have been made, through biotechnological processes, in the production and development of peptides capable of increasing collagen and elastin synthesis for anti-aging skin care. However, proteins have many limitations due to their structural, chemical and physical fragility to external aggressions, which may cause conformational changes, leading to loss of biological activity. Therefore, it is important to create delivery systems that protect these biomolecules from damage, allowing them to reach their target. This work aimed to develop a system able to carry bovine serum albumin (BSA), used as a model of a protein, and to incorporate this system in a semisolid formulation suitable for skin application. A microemulgel based on a solid-in-oil-in-water (S/O/W) microemulsion was prepared. Firstly, the association efficiency (AE) of lyophilized BSA-sucrose ester complex and the size of S/O nanodispersion were assessed; then, the characterization and stability evaluation of the final semisolid formulation through evaluation of pH, texture and rheological behavior were performed. The average value of AE was 54.74% ± 2.17. It was possible to develop an S/O/W microemulsion, which allowed the subsequent development of an S/O/W microemulgel that assured suitable pH, texture and rheological characteristics for skin application.Resumo em Inglês:
Abstract Simple, precise, accurate and specific spectrophotometric methods are progressed and validated for concurrent analysis of Furosemide (FUR) and Spironolactone (SPR) in their combined dosage form depend on spectral analysis procedures. Furosemide (FUR) in the binary mixture could be analyzed at its λmax 274 nm using its recovered zero order absorption spectrum using constant multiplication method (CM). Spironolactone (SPR) in the mixture could be analyzed at its λmax 238 nm by ratio subtraction method (RS). Concurrent determination for FUR and SPR in their mixture could be applied by amplitude modulation method (AM), absorbance subtraction method (AS) and ratio difference (RD). Linearity ranges of FUR and SPR were (2.0µg/mL-22.0 µg/mL) and (3.0µg/mL-30.0 µg/mL), respectively. Specificity of the proposed spectrophotometric methods was examined by analyzing the prepared mixtures in laboratory and was applied successfully for pharmaceutical dosage form analysis which have the cited drugs without additives contribution. The proposed spectrophotometric methods were also validated as per as the guidelines of ICH. Statistical comparison was performed between the obtained results with those from the official methods of the cited drugs, using one-way ANOVA, F-test and student t-test. The results are exhibiting insignificant difference concerning precision and accuracy.Resumo em Inglês:
Abstract Licania macrophylla is a medicinal plant from the Amazon. It is mainly used in the form of a decoction and has been reported to contain several phenolic compounds. However, the effect of seasonality on the phenolic composition and antioxidant potential of this plant has not been well studied, especially in the Amazon region, an area affected by the rainy and less-rainy seasons. Therefore, we evaluated the seasonality of these aromatic compounds and the antioxidant potential of the extracts from L. macrophylla stem bark. We also determined the correlation between the extraction methods used and precipitation levels during each period for 1 year. The total flavonoid and phenolic content, DPPH-scavenging potential, percentage of phosphomolybdenum complex reduction, and iron-reducing power were quantified. The levels of phenolic compounds were the highest in June, whereas those of flavonoids were the highest in September and October; however, these differences were not significant. The extracts from April, November, and June showed the best results for DPPH scavenging, phosphomolybdenum reduction, and iron reduction power, respectively. Significant differences in the phenolic content and DPPH-scavenging activity were observed between the more- and less-rainy seasons. The total phenolic content was positively correlated with FRAP and DPPH, whereas flavonoid levels were negatively correlated.Resumo em Inglês:
Abstract In an attempt to increase molecular stability and provide controlled release, vascular endothelial growth factor (VEGF) was encapsulated into polycaprolactone (PCL) nanoparticles. Both VEGF-free and VEGF-loaded PCL nanoparticles were formulated by w/o/w double emulsion of the dichloromethane-water system in the presence of polyvinyl alcohol (PVA) and rat serum albumin. To achieve the optimal formulation concerning particle size and monodispersity, studies were carried out with different formulation parameters, including PVA concentration, homogenization time and rate. Scanning electron microscopy and dynamic light scattering analysis showed respectively that particles had a spherical shape with a smooth surface and particle size varying between 58.68-751.9 nm. All of the formulations were negatively charged according to zeta potential analysis. In vitro release study was performed in pH 7.4 phosphate-buffered saline at 37°C and released VEGF amount was measured by enzyme-linked immunosorbent assay (ELISA) method. At the end of the 35th day, 10% of total encapsulated VEGF was released with a sustained-release profile, which fitted the Korsmeyer-Peppas kinetic model. The bioactivation of the nanoparticles was evaluated using XTT and ELISA methods. As a result, the released VEGF was biologically active and also VEGF loaded PCL nanoparticles enhanced proliferation of the human umbilical vein endothelial cells in cell culture.Resumo em Inglês:
Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.Resumo em Inglês:
Abstract To assess the therapy relative to indication, effectiveness, safety and adherence in patients with Alzheimer’s disease (AD). An interventional, prospective, non-randomized study was conducted in a single secondary care center in Brazil. The pharmacist-led medication therapy management (MTM) was conducted to detect drug-related problems (DRPs) at baseline and after six months of intervention. The health status outcomes (i.e. cognitive screening tests; levels of glucose; total cholesterol; triglycerides; thyroid stimulating hormone; serum free thyroxine and blood pressure) were measured. 66 patients with AD were included, of whom 55 patients completed the follow-up of six months. 36 patients (36/55) were non-adherent to AD drug therapy. Out of detected 166 DRPs, 116 were solved. Four patients were withdrawn from the AD protocol due to resolution of prodromal symptoms. On the conclusion of the study, the MTM improved and controlled blood pressure, glucose, total cholesterol, triglycerides levels (p<0.05). The pharmacist-led MTM was effective in solving 69.8% of DRPs, improving and controlling the clinical parameters evaluated.Resumo em Inglês:
Abstract A study was carried out to synthesize silver nanoparticles (Ag-NPs) using plant extracts and to explore their pharmaceutical application as antibacterial agents. Dried leaves of Mentha arvensis Linn. were powdered and extracts were prepared using three different organic solvents. Preliminary screening on antibacterial activity by agar well diffusion method indicated that the methanolic extract possessed higher potential than the other two. Phytochemical analysis of the leaf extract revealed that it possesses tannins, steroids, terpenoids and flavonoids. Ag-NPs prepared using this extract were of spherical to cuboidal shape ranging in size from 40 to 70 nm. It retained essential chemical groups and had the required surface plasmon resonance. Further to the antimicrobial assay, the Ag-NPs, in contrast to the whole methanolic leaf extract, showed better (100% vs. 80%) bactericidal activity against the indicator organisms. The zones of growth inhibition for gram positive bacteria ranged between 14±0.6 and 23±0.3, while it was between 12±0.6 and 22±0.2 for gram negative bacteria. The Ag-NPs presented the minimum inhibitory concentration values of 250 µg/mL for gram positive bacteria and 250 - 500 µg/mL for gram negative bacteria. These findings suggest that the natural compounds present in M. arvensis L. possess the potency to facilitate the synthesis and antibacterial action of Ag-NPs.Resumo em Inglês:
Abstract This study aimed to evaluate the effectiveness and safety of direct-acting antivirals in a Unified Health System pharmacy of Londrina, Brazil. A descriptive observational study was performed from June 2017 to June 2018. Sociodemographic, clinical, and therapeutic variables of patients were collected from secondary data sources. Effectiveness was evaluated by sustained virologic response (SVR) and safety was evaluated by adverse events (AEs) and drug interactions (DIs). The mean population (N=30) was 56.6±11.3 years old and almost all patients had comorbidities (93.3%) and concomitant drugs (96.7%). Effectiveness evaluation was possible in 17 patients, and all of them (100.0%) achieved SVR. Eighteen patients (60.0%) reported 38 AEs, mostly mild, such as stomach symptoms and headache. No statistical relation was found between AE occurrence and treatment duration, Ribavirin use, number of comorbidities or number of concomitant drugs. A total of 48 DIs were reported, 18 being severe, and were managed by the pharmacist. The study indicates that the treatment was effective and safe.Resumo em Inglês:
Abstract L-Asparaginase (L-ASNase) is a biopharmaceutical used for acute lymphoblastic leukaemia (ALL) treatment, dramatically increasing the patients’ chance of cure. However, its production and distribution in developing countries were disrupted because of its low profitability, which caused great concern among patients. This study evaluates the feasibility of combining fractional precipitation and aqueous two-phase systems (ATPS) to purify L-ASNase from a low-grade product, commercially known as Acrylaway® L. The ATPS purification results were not particularly expressive compared to the two-step purification process composed of ethanol precipitation and gel filtration, which was able to recover the target molecule with a purification factor over 5 fold. Thus, we studied a purification process capable of manufacturing pharmaceutical grade L-ASNase from a commercially available low-grade raw material; however, improvements regarding its throughput must be achieved, and high purity is the first step to apply it as a new biopharmaceutical product. The proposed process could pose as a short-time solution to mitigate its shortage while a cost-effective production plant is being developed.Resumo em Inglês:
Abstract The present work reports the implementation of the Hazard Analysis Critical Control Point (HACCP) methodology to analyze the water purification system of a pharmaceutical site, in order to assure the system quality and prevent failures. As a matter of fact, the use of HACCP for development and implementation of Quality Risk Management (QRM) is not usual in pharmaceutical plants and it is applied here to improve the performance of the water purification system of a polymerization pilot plant used to manufacture pharmaceutical grade polymer microparticles. Critical Control Points (CCP) were determined with the aid of a decision tree and questions were made to characterize whether identified hazards constitute actual CCPs and should be monitored. When deviations were detected, corrective actions were performed and action plans were used for following-up and implementation of corrective actions. Finally, microbiological and physicochemical parameters were analyzed and the obtained results were regarded as appropriate. Therefore, it is shown that HACCP constitutes an effective tool for identification of hazards, establishment of corrective actions and monitoring of the critical control points that impact the process and the quality of the final pharmaceutical product most significantly.Resumo em Inglês:
Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.Resumo em Inglês:
Abstract The hospital pharmacy needs a constant process of evaluation and monitoring of its activities. In Brazil, several agencies establish tasks and duties for pharmacists, but little is known about the compliance and the perception of the professional regarding these policies. The present study aims to characterize the pharmacist’s perception of Brazilian hospital pharmacy policies according to the Basel Statements. A search was performed for the contacts of all medium and high complexity hospitals in the country. Subsequently, a questionnaire elaborated following the Basel Statements was sent by e-mail to hospital pharmacists throughout the country. The domain analyzed was "Human Resources, Training, and Development". Statistical analyses were performed using SPSS 19.0. Pharmacists representing a total of 111 hospitals from all Brazilian regions answered the survey questionnaire and showed that more than half of the hospital pharmacists perceive themselves as not complying, whether in the service of local, national, or pharmaceutical education. Besides updating the professionals in relation to national policies, it is necessary that the representative bodies of the pharmaceutical class be more present in the elaboration and evaluation of the policies directed to human resources, seeking uniformity and the possibility of carrying out the activities required.Resumo em Inglês:
Abstract The current investigation entail systematic Quality by Design (QbD)-enabled approach for the development of Sustained released embedded drug delivery systems of L-Arginine employing ionic gelation technique to attain improved patient compliance. Hence, in this QbD enabled systematic approach; quality target product profile (QTTP) was defined and critical quality attributes (CQAs) were identified. Further the risk assessment studies were undertaken through Ishikawa fish bone diagram to locate the critical material attributes (CMAs) and/or critical process parameters (CPPs) for the formulation of beads that may affect CQAs of drug product. A face centered central composite design (CCD) for two factors at three levels each with α =1 was employed for the optimization process to checkout the impact of concentration of sodium alginate and concentration of chitosan as CMAs which wereprior identified from risk assessment study and further evaluated for CQAs viz. bead size, swelling index and percent drug entrapment. The optimum formulation was embarked upon by using mathematical model being developed yielding desired CQAs. Thereby chitosan coated calcium-alginate delivery system was successfully developed by strategically employing QbD approach.In a nutshell, the presentinvestigation reports the successful development of optimized chitosan coated alginate beads employing QbD approach which can serve as a platform for other drugs too.Resumo em Inglês:
Abstract Transgender is a broad-spectrum term referring to people who do not match their assigned sex at birth. Several issues, including social detachment, poor access to healthcare services, and the lack of social/economic opportunities, have historically affected this population. In this scenario, pharmacists - not mentioned in national and international clinical guidelines/protocols regarding transgender care - might be key professionals to serve and care for this population. The main goal of this literature review was to identify the pharmacists’ role in the care of transgender people. The articles were retrieved from scientific databases. After applying filters (e.g., language, full-text availability, and coverage of the research question), seven articles were included in this review. The articles did not present pharmaceutical experiences or practices regarding transgender healthcare. Instead, some articles stressed the inadequate or inappropriate use of hormones and their side effects, also covering the role of this issue in professional development, gaps, and potential opportunities for research and pharmaceutical services. Pharmacists, included in a multi-professional team, could be a key element to promote access to healthcare and the well-being of the transgender population.Resumo em Inglês:
Abstract Exopolysaccharides (EPS) produced by Klebsiella oxytoca are of environmental, pharmaceutical, and medicinal interest. However, studies about the anti-inflammatory activity of EPS produced by this microorganism still remain limited. The aim of this study was to produce, characterize, and evaluate the anti-inflammatory activity of EPS from K. oxytoca in a pleurisy model. Colorimetric analysis revealed that precipitated crude exopolysaccharides (KEPSC) and deproteinated exopolysaccharides (KEPS) present high levels of total carbohydrates (65.57% and 62.82%, respectively). Analyses of uronic acid (7.90% in KEPSC and 6.21% in KEPS) and pyruvic acid (3.01% in KEPSC and 1.68% in KEPS) confirm that the EPS are acidic. Gas chromatography-mass spectrometry analyses demonstrated that the EPS consisted of rhamnose (29.83%), glucose (11.21%), galactose (52.45%), and mannose (6.50%). The treatment of an experimental pleurisy model in rats through subcutaneous administration of 50, 100, 200, and 400 mg/kg of KEPS decreased both the volume of inflammatory exudate and the number of leukocytes recruited to the pleural cavity. The present data showed that EPS production by K. oxytoca using the method described is easy to perform and results in a good yield. In addition, we show that KEPS exhibit anti-inflammatory activity when administered subcutaneously in rats.Resumo em Inglês:
Abstract This study aimed to evaluate the antioxidant potential of the Coffea arabica Lineu (L.) leaf extract and its effects on platelet aggregation of dyslipidemic rats. The extract was obtained by the percolation of C. arabica L. leaves in hydroethanolic solution 70% (v/v). The mass spectrometry FIA-ESI-MS² suggested the presence of chlorogenic acid, rutin acid, and quinic acid. The DPPH• radicals scavenging capacity was demonstrated (IC50 = 0.06 mg/mL). The extract was administered to rats by gavage (300 mg/kg/day) for 56 days. Dyslipidemia was induced by administering Triton WR-1339 (300 mg/kg body weight) on the 54th day. On day 56, blood was collected by puncturing the abdominal aorta artery and the aortic artery was removed. Lipid profile, markers of renal and hepatic injury, lipid peroxidation, and platelet aggregation tests were carried out. The ingestion of extract reduced the lipid peroxidation (aorta and plasma) and platelet aggregation in dyslipidemic rats. The extract did not affect markers of renal and hepatic function as analyzed in this study, suggesting neither impaired liver nor kidney function in these animals. Therefore, our results demonstrate that the extract of leaves of C. arabica L. show antioxidant potential in vitro and in vivo as well as anti-platelet aggregation in dyslipidemic animals.Resumo em Inglês:
Abstract Neonatal sepsis continues to be a major cause of morbidity and mortality worldwide. Coagulase-negative staphylococci (CoNS), commonly found on the skin, being the main agents isolated. The aim of this study was to evaluate CoNS isolated from blood cultures of newborn (NB) infants. The study took place between 2014 and 2016/2017 in a tertiary hospital in southern Brazil. Using the VITEK 2 system (bioMérieux, Marcy l'Etoile, France), the microorganisms were identified and had their sensitivity profiles determined. The minimum inhibitory concentrations of linezolid, tigecycline, and vancomycin were also determined. The clinical parameters and mortality rates of NBs were evaluated. From January to December 2014, 176 CoNS isolates were obtained from 131 patients and from June 2016 to July 2017, 120 CoNS isolates were obtained from 79 patients. Staphylococcus epidermidis was most prevalent in both periods. Resistance rates increased between 2014 and 2016/2017, especially against ciprofloxacin (52.27% and 73.11%, p = 0.0004), erythromycin (51.40% and 68.07%, p = 0.0054), gentamicin (50.59% and 67.23%, p = 0.0052), and penicillin (71.3% and 99.17%, p = 0.0001), respectively. With 100% susceptibility to linezolid, tigecycline, and vancomycin in both periods and methodologies tested. In 2014, 53.44% of the NBs received antibiotic therapy, and of these, 77.14% used a catheter; in 2016/2017, these were 78.48% and 95.16%, respectively. Regarding laboratory tests, a hemogram was ineffective, since patients with sepsis presented normal reference values. In 2014 and 2016/17, 15.71% and 17.74% of the NBs died, respectively. S. epidermidis was the predominant microorganism, related to catheter use in most cases. The resistance rates have increased over time, demonstrating the importance of adopting control and prevention measures in this hospital. CoNS are responsible for a significant neonatal sepsis mortality rate in infants.Resumo em Inglês:
Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.Resumo em Inglês:
Abstract Passiflora nitida Kunth, an Amazonian Passiflora species, is little studied, although the specie’s high biological potential. Herein the plant’s pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent. P. nitida dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1 and tyrosinase inhibition between 400-654 μg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that P. nitida extract has promising features for the development of cosmetic formulations.Resumo em Inglês:
Abstract In the recent past, drug delivery through nanoparticles is considered an effective tool to treat various diseases. Biopolymeric nanoparticles such as protein based nanoparticles have vital role as drug carrier as it is non-antigenic, and easily biodegradable. Curcumin, plant polyphenolic anticancerous compound was loaded into the casein nanoparticles by coacervation method. Particle size and surface charge of spherical casein nanoparticles as observed to be 201.4 nm and -86.9 mV. The loading efficiency of curcumin loaded casein nanoparticles was found to 85.05 %. In vitro drug release was performed at different pH (7.4 and 3.0), and the cumulative release was observed to be 24.8 and 20.13% and at different temperatures (25°C and 37°C), the cumulative release was observed to be 24.8 and 28.60 % respectively in 48 h. Curcumin release from casein nanoparticles was shown to be in a steady, and prolonged rate. The nanoparticles were observed to have an effective antimocrobial activity than curcumin in free form. The drug loaded casein nanoparticles were found to be potent particles to protect cells from hydrogen peroxide and UV light damage. The cytotoxic activity of nanoparticles on MCF7 and A549 cells were assayed and was observed to have an IC50 value of 609 and 825.2µg/ml. Cell death was observed to be through apoptosis, accompanied by DNA fragmentation.Resumo em Inglês:
Abstract Medication reconciliation is a strategy to minimize medication errors at the transition points of care. This study aimed to demonstrate the effectiveness of medication reconciliation in identifying and resolving drug discrepancies in the admission of adult patients to a university hospital. The study was carried out in a 300-bed large general public hospital, in which a reconciled list was created between drugs prescribed at admission and those used at pre-admission, adapting prescriptions from the pharmacotherapeutic guidelines of the hospital studied and the patients’ clinical conditions. One hundred seven patients were included, of which 67,3% were women, with a mean age of 56 years. Two hundred twenty-nine discrepancies were found in 92 patients; of these, 21.4% were unintentional in 31.8% of patients. The pharmacist performed 49 interventions, and 47 were accepted. Medication omission was the highest occurrence (63.2%), followed by a different dose (24.5%). Thirteen (26.5%) of the 49 unintentional discrepancies included high-alert medications according to ISMP Brazil classification. Medication reconciliation emerges as an important opportunity for the review of pharmacotherapy at transition points of care, based on the high number of unintentional discrepancies identified and resolved. During the drug reconciliation process, the interventions prevented the drugs from being misused or omitted during the patient’s hospitalization and possibly after discharge.Resumo em Inglês:
Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 μg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines.Resumo em Inglês:
Abstract Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 μ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer.Resumo em Inglês:
Abstract Posaconazole exerts an extended spectrum of antifungal activity against various strains of clinically relevant moulds and yeasts. In recent years, antifungal triazole posaconazole has become increasingly important for the prophylaxis and treatment of systemic mycoses. After oral administration of posaconazole, absolute bioavailability has been estimated to range from 8% to 47%. Pharmaceutical co-crystallization is a promising approach for improving dissolution rate or manipulating other physical properties of API. The objective of this study is to improve the dissolution rate of posaconazole by co-crystallization. A 1:1 stoichiometric co-crystals of adipic acid were prepared by solvent assisted grinding method. The prepared co-crystals were subjected to solid-state characterization by FTIR, PXRD and DSC studies. The physicochemical properties of posaconazole and co-crystals were assessed in terms of melting point, flowability and dissolution rate. The results indicated improvement in flow property and dissolution rate. In vitro dissolution profile of co-crystals showed a significant increased dissolution of posaconazole from initial period in 0.1 N hydrochloric acid solution. The dissolution efficiency for posaconazole-adipic acid co-crystal was 61.65 % against posaconazole, 46.58 %. Thus, co-crystallization can be a promising approach to prepare posaconazole-adipic acid co-crystals with improved physicochemical properties.Resumo em Inglês:
Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.Resumo em Inglês:
Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.Resumo em Inglês:
Abstract The objective of this study was to determine the influence of nonionic surfactants on the effectiveness of preservatives used in emulsions containing high surfactant content. Mixtures of different concentrations were prepared between polyethoxylated (40) hydrogenated castor oil (PHCO) and polyoxyethylene sorbitan monooleate (PSO), with methylparaben, phenoxyethanol, methylparaben, ethylparaben, propylparaben, and isobutylparaben (PMEPBI) blend, phenoxyethanol and benzoic acid (BP) blend, and phenoxyethanol and caprylyl glycol (PC) blend. Subsequently, the compatibility of the formulation ingredients and the effectiveness of the preservatives were evaluated by the challenge test. It was found that PHCO and PSO inactivated the antimicrobial action of methylparaben and PMEPBI. Paraben-free preservatives BP and PC had less influence on surfactants than systems containing parabens. When incorporated into microemulsions and nanoemulsions containing 40% and 20% surfactants, methylparaben and BP 0.2% and 0.5% were only effective against Aspergillus niger. The PMEPBI 0.2% was effective as a preservative in nanoemulsified formulations against A. niger, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results demonstrate that the efficacy of the preservative system in formulations containing nonionic surfactant excipients depends on the type of excipient, the components of the formulation, the preservative systems composition, the excipient to preservative ratio, and the availability in the formulation.Resumo em Inglês:
Abstract The objective of this study is to validate the specific questionnaire for Hepatitis B HBQOL (Hepatitis B Quality of Life Instrument, version 1.0) for the Brazilian version, in addition to testing its applicability in patients with hepatitis B under treatment and comparing the quality of life between patients using first-line drugs (tenofovir and entecavir). For the validation, the back-translation technique was used in a sample of 47 patients. Factor analysis was performed between the items in each domain of the questionnaire and the internal consistency was calculated using Cronbach's α coefficient. In assessing the applicability of the validated questionnaire, interviews were carried out with 124 patients. Sociodemographic and treatment data were collected to characterize the sample and perform correlation analyzes. The results demonstrate that the Brazilian version of the questionnaire was successfully validated. In the analysis carried out among the 124 patients, the domains psychological well-being and stigma obtained the highest scores in quality of life and the lowest level of education conferred better results in these two domains. The comparison between tenofovir and entecavir showed no significant difference in patients' quality of life. The use of this validated instrument can make therapeutic decisions more rational.Resumo em Inglês:
Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.Resumo em Inglês:
Abstract Snakebite is one of the major health issues posing considerable morbidity and mortality. According to an estimate of World Health Organization (WHO) (World health organization, 2021) approximately 5 million people are bitten by several species of snakes resulting in up to 2.5 million envenomation cases annually. The mainstay of treatment for envenomation is intravenous administration of anti-snake venom. Although antivenom neutralizes the systemic effects but it does not relieve the symptoms such as venom-induced hemorrhage, necrosis and nephrotoxicity. Moreover, the use of antivenoms is associated with hypersensitivity reactions including urticaria, anaphylaxis, or serum sickness due to their heterologous property. Furthermore, stringent storage conditions and narrow specificity of antivenoms limit their use in both developed as well as developing countries. In this context, researchers have been searching for natural products and plant extracts to explore their antivenom activity along with anti-myotoxic, anti-hemorrhagic and anti-inflammatory properties. Plant remedies may prove to be an effective alternate for antivenom sera with less adverse events and better tolerability. To the best of our knowledge, this is the first comprehensive review of medicinal plants possessing anti-snake venom activities against certain species of snakes. The current review highlights the investigated plants with their phytochemical analysis to integrate the available information for future research and development of antivenom sera.Resumo em Inglês:
Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1β, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1β, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination.Resumo em Inglês:
Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.Resumo em Inglês:
Abstract Existing medications i.e. the antipsychotic drugs are known to be effective in treating only the positive symptoms of schizophrenia, while being ineffective on negative and cognitive symptoms of the disease. In addition, these medications cause extrapyramidal symptoms, forcing many patients towards natural medicine in the hope of minimizing the unwanted adverse effects. Nardostachys jatamansi is a medicinal plant that has been traditionally prescribed for various types of brain disorders. The active constituents of the plant have beneficial effects on the negative and cognitive symptoms of schizophrenia. This study was designed to identify the active constituents of Nardostachys jatamansi with the highest binding affinities for the key macromolecular drug targets involved in the pathophysiology of schizophrenia and thereby elucidate the possible mechanism of action. These targets are dopamine receptors, Gamma-aminobutyric acid receptors, N-methyl-D-aspartate receptors and Phosphodiesterase 10A. The results of molecular docking showed that, β-sitosterol, chlorogenic acid, oleanic acid and ursolic acid, displayed high binding affinity toward all the macromolecular drug targets. Ligands with steroid backbone and pentacyclic triterpene structure have been found to possess high binding affinity toward the dopamine receptor and phosphodiesterase 10A. While ligands with carbonyl group form stronger binding interactions with the N-methyl-D-aspartate receptor.Resumo em Inglês:
Abstract A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease.Resumo em Inglês:
Abstract The prolonged entry of large amounts of calcium into the mitochondria through the mitochondrial calcium uniporter complex (MCUC) may cause the permeability transition pore (mPTP) to open, which contributes to the pathogenesis of several diseases. Tissue-specific differences in mPTP opening due to variable expression of MCUC components may contribute to disease outcomes. We designed this study to determine differential mPTP opening in mitochondria isolated from different regions of mouse brain and kidney and to compare it with the expression of MCUC components. mPTP opening was measured using mitochondria isolated from the left/right brain hemispheres (LH/RH, respectively) and from kidney cortex/medulla, while the expression level of MCUC components was assessed from total cellular RNA. Interestingly, LH mitochondria showed less calcium-induced mPTP opening as compared to RH mitochondria at two different calcium concentrations. Conversely, mPTP opening was similar in the renal cortex and renal medulla mitochondria. However, the kidney mitochondria demonstrated bigger and faster mPTP opening as compared to the brain mitochondria. Furthermore, asymmetric mPTP opening in the LH and RH mitochondria was not associated with the expression of MCUC components. In brief, this study demonstrates thus far unreported asymmetric mPTP opening in mouse brain hemispheres that is not associated with the mRNA levels of MCUC components.Resumo em Inglês:
Abstract The study aimed to assess possible spirulina effects on lipid profile, glucose, and malondialdehyde levels in new cases of type 2 diabetes. The subjects consisted of 30 new cases of types 2 diabetes that divided into two groups; each consisted of 15 diabetic patients. Group I did not take any functional food or supplement and received no spirulina supplementation. Group II or experimental group also did not take any functional food or supplement but received spirulina supplementation. Analysis of data was done using SPSS 16.0. The Kolmogorov-Smirnov test, paired t-test, Wilcoxon test, and Spearman correlation analysis were used to analyze the data. After eight weeks of spirulina supplementation, significant differences were shown in the serum levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and malondialdehyde. The serum fasting blood glucose, lipid profiles, and malondialdehyde levels at baseline were negatively and positively correlated with changes in these parameters. Spirulina supplementation may have a beneficial effect on lipid profile and malondialdehyde (MDA) levels through an interventional 8 weeks. This effect may protect subjects against free radicals and the development of some diseases such as atherosclerosis. The spirulina supplementation also showed a potential lipid-lowering effect on new case type 2 diabetic patients which may help the diabetics to have control on lipid levels. In addition, spirulina may be used as a functional food for the management of lipid profiles and MDA levels.Resumo em Inglês:
Abstract The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-β-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-β-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-β-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.Resumo em Inglês:
Abstract We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC.Resumo em Inglês:
Abstract Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPβCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability.Resumo em Inglês:
Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.Resumo em Inglês:
Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5βH-9βH-iridoid-1α-O-(6′-O-(6,7-dihydrofoliamenthonyl)-β-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6′-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal.Resumo em Inglês:
Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.Resumo em Inglês:
Abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling.Resumo em Inglês:
Abstract This study highlights the cytotoxic effect of three L. casei strains on colorectal cell lines in invitro conditions. Different concentrations of live, heat killed (HK) and cell free supernatant (CFS) of three L.casei strains were subjected to CaCo2 and MRC5 cell lines. The viability of the treated and untreated cells was determined after 72 hrs by MTT assay, and IC50 estimated. Apoptosis was evaluated by Annexin V-propidium iodide method using flow cytometry. The live, HK and CFS of the L. casei strains showed cytotoxic effects on colorectal cell lines with significant differences. The cytotoxicity effects of live cells on CaCo2 cells were significantly higher (p˂0.01) than the HK cells. A dose dependent response was observed, as higher concentrations resulted in enhanced cytotoxicity effects. Live L.casei 1296-2cells inhibited 91% of CaCo2 cell growth, with IC50 of less than 108 cfu/ml. MRS medium and concentrations of CFS at above 20% v/v, were cytotoxic to the normal cell lines. Flow cytometry analyses of L. casei 1296-2 indicated that cytotoxicity effects on CaCo2 cells is related to apoptotic induction. Invitro studies indicate that Live and CFS of L. casei 1296-2 might be promising candidate for the control of colorectal cancers.Resumo em Inglês:
Abstract In the epistemic field, several studies demonstrate the importance of pharmaceutical services in health care networks. Nonetheless, literature still addresses the strengths and barriers present in the provision of these services in an incipient way. Thus, this study aimed to understand these contexts in the development of clinical services for primary health care in the Federal District, Brazil. A qualitative study adopted the technique of open-script interview, structured based on the logic of the SWOT matrix. Pharmacists reported weaknesses such as precariousness and scarcity of physical infrastructure, material, and human resources. As threats, they discussed the lack of social recognition, discontinuities of government actions, and lack of preparation of the pharmacist for the provision of clinical services. Regarding themes pertaining to the service’s strengths and opportunities, the advances in propositions and executions of public policies, actions, and governmental programs that have expanded the pharmaceutical workforce in primary care and that are impelling the accomplishment of clinical services were listed. This study contributes to understanding the scenario of the development of clinical pharmaceutical services, and consequently provides subsidies for the actions of planning, evaluation and qualification of health services.Resumo em Inglês:
Abstract Pharmaceutical services correspond to a set of actions that aim to guarantee the integral access and rational use of drugs by the population. In this sense, this study aimed to identify the frequency and conditioning factors for clinical services of primary care in the Federal District, Brazil. A quantitative cross-sectional study was conducted, in which 34 pharmacists were interviewed. The most frequently developed clinical pharmaceutical services were dispensing, pharmaceutical guidance for users, and technical-pedagogical activities for the health team. There is a greater frequency of operation of clinical services by pharmacists working in pharmacies with physical infrastructure, with better levels of adequacy, greater support from management and health staff, and the inclusion in Family Health Support Nucleus activities. Although the clinical pharmaceutical services in primary care are incipient, the study raises important data for the reorientation and qualification of these actions.Resumo em Inglês:
Abstract Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid.Resumo em Inglês:
Abstract Dyslipidemia is an abnormal lipid profile associated with many common diseases, including coronary heart disease and atherosclerosis. Cholesteryl ester transfer protein (CETP) is a hydrophobic plasma glycoprotein that is responsible for the transfer of cholesteryl ester from high-density lipoprotein athero-protective particles to pro-atherogenic very low-density lipoprotein and low-density lipoprotein particles. The requirement for new CETP inhibitors, which block this process has driven our current work. Here, the synthesis as well as the ligand-based and structure-based design of seven oxoacetamido-benzamides 9a-g with CETP inhibitory activity is described. An in vitro study demonstrated that most of these compounds have appreciable CETP inhibitory activity. Compound 9g showed the highest inhibitory activity against CETP with an IC50 of 0.96 μM. Glide docking data for compounds 9a-g and torcetrapib provide evidence that they are accommodated in the CETP active site where hydrophobic interactions drive ligand/CETP complex formation. Furthermore, compounds 9a-g match the features of known CETP active inhibitors, providing a rationale for their high docking scores against the CETP binding domain. Therefore, these oxoacetamido-benzamides show potential for use as novel CETP inhibitors.Resumo em Inglês:
Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.Resumo em Inglês:
Abstract The consumption of cosmetics has been increasing every year and is expected to reach $675 billion by 2020 at an estimated growth rate of 6.4% per year. Exposure to skin irritants is the major cause of non-immunological inflammation of the skin. Therefore, the safety evaluation of cosmetic preservatives should be increased. Thus, the present work aimed to evaluate the cytotoxicity as the viability endpoint and the eye irritation potential of preservatives used in cosmetics. Cytotoxicity assays were performed using MTT and NRU in human keratinocytes (HaCaT), human dermal fibroblasts, adult (HDFa), and human hepatoma cells (HepG2). The eye irritation potential was evaluated using the Hen’s Egg Test-chorioallantoic membrane (HET-CAM). The evaluated preservatives were methylparaben (MP), propylparaben (PP), phenoxyethanol (PE), and a mixture of methylchloroisothiazolinone and methylisothiazolinone (CMI/MI). All preservatives showed cytotoxic potential within the permitted concentrations for use in cosmetic products. In the HET-CAM test, PE and CMI/MI, MP, and PP were classified as severe, moderate, and poor irritants, respectively. Our results indicate that proper safety evaluations are required to ensure the beneficial properties of preservatives on cosmetic products without exceeding exposure levels that would result in adverse health effects for consumers.Resumo em Inglês:
Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.Resumo em Inglês:
Abstract Glucose exposure induces toxic effects on the function of the pancreatic islets. Moreover, myricitrin as a flavonoid glycoside may have favorable effects on insulin secretion of Langerhans islets. The present study aimed to investigate the effect of Myricitrin and its solid lipid nanoparticles (SLN) on the insulin secretion as well as the content of isolated pancreatic islets from male mice. In this experimental study, Langerhans islets were separated from adult male NMRI mice using the collagenase method. The insulin secretion and content of islets were assessed in glucose-containing medium (2.8, 5.6, and 16.7mM). Further, islets treated were prepared by the administration of Myricitrin and its SLN (1, 3 and 10µM). Myricitrin 3μM, and SLN containing Myricitrin 3 and 10μM increased insulin secretion in medium containing glucose concentration 2.8mM. Accordingly, this variable increased in Myricitrin 3 and 10μM, SLN containing Myricitrin 1, 3, and 10μM utilization as well as glucose concentration 5.6mM. Afterward, the insulin secretion increased in medium containing 16.7mM glucose after the addition of Myricitrin and SLN containing Myricitrin 1, 3, and 10μM. Also, the insulin content increased in Myricitrin and SLN containing Myricitrin 1, 3, and 10μM administered groups in all medium containing glucose concentrations. Myricitrin and its SLN increased islets insulin secretion and content in low, moderate, and high glucose concentration mediums.Resumo em Inglês:
Abstract Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders.Resumo em Inglês:
Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter’s test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.Resumo em Inglês:
Abatsract Pseudomonas aeruginosa is an important nosocomial pathogen and its clinical importance is mainly related to nosocomial infections. Increased rates of bacterial resistance in recent years has led WHO to publish a global priority list to guide research and discovery of new antibiotics, where P. aeruginosa is among the group of bacteria for which there is a critical level of priority for new drugs to be discovered. In this context, isoeugenol appears as an interesting alternative and the objective of this study was to investigate its action against P. aeruginosa. Isoeugenol presented significant antibacterial activity, with minimum inhibitory concentration (MIC) of 64µg/mL and minimum bactericidal concentration (MBC) of 128µg/mL, and was considered bactericidal against this species. Molecular docking revealed interactions that suggest that isoeugenol may bind to the enzyme Penicillin-Binding Protein 3 and interfere with the bacterial cell wall synthesis process. This study reinforces the antibacterial potential of this compound and emphasizes that more studies are needed in order to better investigate its mechanism of antibacterial action.Resumo em Inglês:
Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr’s index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.Resumo em Inglês:
Abstract Caveolin, the protein of the caveolar membrane, interacts and binds with endothelial nitric oxide synthase (eNOS), forming a caveolin-eNOS complex leading to suppression of the eNOS activity. Caveolin, therefore, maintains eNOS in the inactivated state leading to reduced nitric oxide (NO) production. Ischemic preconditioning disrupts the caveolin-eNOS complex leading to activation of the eNOS and thus results in cardioprotection. During ischemic preconditioning, NO produces cardioprotection by the opening of the KATP channel, and the caveolin forms a suitable signalling platform facilitating the interaction of NO with the KATP channel. Estrogen deficiency has been reported to upregulate caveolin-1 expression. The article aims to review the various mechanisms that placed the women at the risk of coronary artery diseases after postmenopausal estrogen deficiency and their role in the cardioprotective effect of ischemic preconditioning.Resumo em Inglês:
Abstract Regeneration of damaged kidney cells using stem cells is the current research approach in the treatment of chronic renal failure (CRF). In the present study, the histopathological and biochemical techniques were used to evaluate stem cells’ (SCs) role in treatment of CRF. Sixty-four rats were divided into eight groups. Group I (GI): rats were injected with doxorubicin (15 mg/kg) to initiate CRF. GII-GVII: rats were injected with doxorubicin and treated with SCs (1x106 MSCs or/and 2x104 HSCs/rat) with/without growth factors extract (200 µL/rat) and/or immunosuppressor (cyclosporine A, 5 mg/kg/day). GVIII: rats treated with PBS (100 µL/kg/day). Levels of creatinine, urea and uric acid were increased in rats sera after injection with doxorubicin, while blood electrolyte levels of Na, K, P and Mg were decreased. Also, histopathological abnormalities such as hyalinized blood vessels, degenerated hyalinized glomerulus tubules and cell debris in the lumen and degeneration of renal tissues were observed in these rats. After treatment with SCs, all these parameters restore their normal values with regeneration of the damaged cells as demonstrated in histopathology of the treated groups. It can be concluded that, the use of SCs in treatment of kidney diseases is a promising approach and needs more efforts.Resumo em Inglês:
Abstract Dexchlorpheniramine is a first-generation classical antihistamine, clinically used to treat allergies. The main objective of our study was to evaluate the effects of the dexchlorpheniramine reference standard (DCPA Ref. St) and a pharmaceutical formula on DNA in human peripheral blood mononuclear cells (PBMCs). We exposed PBMCs to five different concentrations (0.5, 2.5, 5, 10, and 50 ng/mL) of DCPA Ref. St DCPA Ref. St and pharmaceutical formula in order to evaluate their cytotoxic, genotoxic, and mutagenic potential. The results showed that both dexchlorpheniramine formulations did not affect PBMC viability and CD3+, CD4+, or CD8+ lymphocyte subpopulations. The DCPA Ref. St and pharmaceutical formula neither induced genotoxic or mutagenic effects nor numerical or structural chromosomal alterations in PBMCs after 24 hours of exposure.Resumo em Inglês:
Abstract Ligustrazine is widely used for the treatment of cardiovascular diseases in traditional Chinese medication. It has been reported that Ligustrazine decreases the concentration of intracellular calcium ions (Ca2+); however, the underlying mechanism remains unknown. In the present study, the effect of Ligustrazine on adenosine diphosphate (ADP)-induced platelet aggregation was evaluated using a turbidimetric approach. The changes in concentration of intracellular Ca2+ stimulated by ADP was measured using fluo-4, a fluorescent Ca2+ indicator dye. The mRNA expression of stromal interaction molecule l (STIM1) and Orai1, calcium sensor, was determined using real-time PCR. In addition, the protein expression of STIM1, Orai1, and serum/glucocorticoid-regulated protein kinase 1 (SGK1) was determined using Western blot analysis. The data demonstrated that Ligustrazine significantly suppressed platelet aggregation in a dose-dependent manner and reduced the concentration of intracellular Ca2+ triggered by ADP. Our data showed that Ligustrazine treatment inhibited the expression of STIM1 and Orai1 induced by ADP at both mRNA and protein levels, and suppressed the protein expression of SGK1. Taken together, our data indicated that Ligustrazine suppressed platelet aggregation by partly inhibiting the activities of calcium sensors, thereby suggesting that Ligustrazine may be a promising candidate for the treatment of platelet aggregation.Resumo em Inglês:
Abstract Molecular mechanisms involved in the development of muscle pain induced by static contraction are not completely elucidated. This study aimed to evaluate the involvement of the transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1) receptors expressed in peripheral and central terminals of primary afferents projected to gastrocnemius muscle and spinal cord in muscle pain induced by static contraction. An electrical stimulator provided the contraction of rat gastrocnemius muscle and mechanical muscle hyperalgesia was quantified through the pressure analgesimeter Randall-Selitto. AMG9810 and HC030031 were used. When administered in ipsilateral, but not contralateral gastrocnemius muscle, drugs prevented mechanical muscle hyperalgesia induced by static contraction. Similar results were obtained by intrathecal administrations. We propose that, in an inflammatory muscle pain, peripheral and central TRPV1 and TRPA1 work together to sensitize nociceptive afferent fibers, and that TRPV1 and TRPA1 receptors are potential target to control inflammatory muscle pain.Resumo em Inglês:
Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1β and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1β (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.Resumo em Inglês:
Abstract In this study, microemulsions containing etofenamate were prepared and evaluated as dermal delivery carriers. The developed microemulsions consist of oleic acid, Span 80, Tween 20, Cremophor EL, Transcutol and ethanol. The percentage of etofenamate loading in the microemulsions was 5% (w/w). The characterization of formulations included droplet size, zeta potential, pH, conductivity, PDI, refractive index and viscosity. Moreover, ex vivo penetration study was carried out using mice abdominal skin. The developed formulations were analyzed for their cytotoxicity via MTT assay and tested for their anti-inflammatory properties opposed to LPS-stimulated nitrite prοduction in RAW 264.7 cells. As ideal formulation, M2ETF, was chosen due to its greater permeation, lower penetration as well as higher anti-inflammatory activity compared to other microemulsions.Resumo em Inglês:
Abstract The purpose of this research was to develop a hydrogel containing the extract of Gac fruit (Momordica cochinchinensis Spreng) with appropriate physicochemical properties and good dermatological efficacy. The Gac aril fruit was extracted by maceration in dichloromethane, and its antioxidant activity was determined through a DPPH assay. The very low water-solubility of the Gac extract is responsible for its incompatibility with the hydrogel. To overcome this drawback, LabrafacTM PG and Tween 60 were used to develop the hydrogel due to their potent potential for solubilizing the Gac extract. The prepared hydrogels displayed good physical properties, a homogenous orange gel, appropriate pH, and viscosity. After storage in an accelerated condition for six months, the hydrogels of the Gac extract had physical stability and high remaining amounts of beta-carotene and lycopene within the range of 90.25 - 94.61%. The skin efficacy of hydrogel containing the Gac fruit extract was found using 14 healthy female volunteers over a 30-day period of daily application. Topical application of the hydrogel containing the Gac fruit extract, which contains antioxidants, significantly moisturizes the skin and enhanced its elasticity (p ≤ 0.05; ANOVA). This makes it suitable for use as a skin care product.Resumo em Inglês:
Abstract The Brazilian native species Cestrum intermedium, known as mata-boi, induces hepatotoxicity and death when ingested by cattle. While most studies on this species focus on toxicological features, our study is the first to describe the anatomy and in vitro biological activities of Cestrum intermedium. We investigated adult leaves and stems by histochemistry, described their anatomy, performed physical-chemical analysis, determined in vitro antioxidant and antimicrobial activities, and identified secondary metabolites. A few noteworthy anatomical features were the anomocytic stomata on the abaxial surface and the absence of trichomes, in addition to the circular shaped petiole with two projections on the adaxial surface. Histochemical analysis showed chemical markers such as alkaloids, usually reported as toxic, and terpenoids. Potassium nitrate (ATR-FTIR) and lupeol palmitate (NMR) were detected on the crude stem extract. Thermogravimetric and physical-chemical analysis provided fingerprint parameters for the species. Minimal Inhibitory Concentration (MIC) assay revealed that Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were weakly inhibited by extract samples. Chloroform and ethyl acetate fractions presented high phenolic content, which resulted in in vitro antioxidant activity. These novel features expand the knowledge about this species, considering that previous studies mainly focused on its toxicity. Our study also provided characteristics that may help in avoiding misidentification between Cestrum members, especially when taxonomic keys cannot be employed, as in the absence of flowers and fruits.Resumo em Inglês:
Abstract This was a forthcoming study of those patients, who undergo in-vitro fertilization (IVF) and freeze-all embryo, who acquiesce for the study. The number of participated patients (n=350) in this study, underwent for IVF. The blood sample was collected from patients to evaluate the level of serum progesterone in vacuum vials on the day of ovulation trigger. After 36 hrs of ovulation trigger, ovum picked up was done. Quantitative methods were used to estimate the level of serum progesterone through the electrochemiluminescence immunoassay and correlation of serum progesterone with embryo transfer (ET) outcomes. Main outcome of this current study was to evaluate the value of mean serum progesterone level i.e.0.868± 0.712 ng/ml and 0.88±0.723 ng/ml was found in case of pregnancy positive and negative respectively, at p=0.216 value. In antagonist (n=40) and agonist (n=310) cases, it was 8(20%) and 37(11.94%) PL occurrence was noted at p=0.143 respectively. An overall value of the premature lutenization (PL) occurrences was 13.63% and 15.25% observed in both positive and negative cases of pregnancy at p=0.216 respectively. This study concluded that 12.66% of PL occurrences were recorded in the case of IVF. Study results proved, there were no significant effect of PL on pregnancy outcomes.Resumo em Inglês:
Abstract Pharmacokinetic studies were carried out in male and female rats to quantify silymarin as silybin (A+B) after the oral administration of various silymarin formulations combined with three bioenhancers, namely, lysergol, piperine, and fulvic acid, and compared with plain silymarin formulation (control). A non-compartmental analysis, model independent analysis, was utilized, and various pharmacokinetic parameters (C max, T max, and AUC 0-t) were calculated individually for each treatment group, and the values were expressed as mean ± SEM (n = 6). Plasma samples obtained from the rats were analyzed for the concentration of silymarin through a validated RP-HPLC method and on the basis of data generated from the pharmacokinetic studies. Results indicated that the bioenhancers augmented pharmacokinetic parameters and bioavailability increased 2.4-14.5-fold in all the formulations compared with the control. The current work envisages the development of an industrially viable product that can be further subjected to clinical trials and scientifically supports the development of silymarin as a contemporary therapeutic agent with enhanced bioavailability and medicinal values.Resumo em Inglês:
Abstract Metabolic syndrome (MetS), an epidemic defined as a group of interconnected physiological, biochemistry, clinical, and metabolic factors, directly increases the risk of cardiovascular disease, atherosclerosis, type 2 diabetes, and death. MetS therapy includes diet, physical exercise, and a poly-pharmacological intervention. Cannabis is mainly recognized for its recreational uses and has several medical applications for neurological diseases, due to its hypnotic, anxiolytic, antinociceptive, anti-inflammatory, and anticonvulsant activities. Although several clinical observations in Cannabis smokers suggest metabolic effects, its utility in metabolic disorders is unclear. This review aims to determine under what conditions Cannabis might be useful in the treatment of MetS. Cannabis contains 120 phytocannabinoids, of which Δ9-THC mediates its psychoactive effects. Cannabinoids exert biological effects through interactions with the endocannabinoid system, which modulates several physiologic and metabolic pathways through cannabinoid receptors (CB1/CB2). Signaling through both receptors inhibits neurotransmitter release. In general, endocannabinoid system stimulation in Cannabis smokers and Δ9-THC signaling through CB1 have been implicated in MetS development, obesity, and type 2 diabetes. In contrast, CB1 antagonists and non-psychotropic phytocannabinoids like cannabidiol reduce these effects through interactions with both cannabinoid and non-cannabinoid receptors. These pharmacological approaches represent a source of new therapeutic agents for MetS. However, more studies are necessary to support the therapeutic potential of Cannabis and cannabinoids in metabolic abnormalities.Resumo em Inglês:
Abstract Two polyurethane foam-based sorbents (PUF) were synthesized by imprinting and grafting techniques and examined for selective separation and preconcentration of caffeine (CAF) in some pharmaceutical products and in black tea. Molecularly imprinted PUF was synthesized based on hydrogen-bonding interactions between CAF and alizarin yellow G (AYG) and subsequent polymerization into PUF. The static experiments indicated optimum sorption conditions at pH=6.5 and 5.5 for imprinted PUF (AY-IPUF) and grafted PUF (AY-GPUF), respectively. In the online experiments, the suitable preconcentration time was found to be 40 and 20s for (AY-IPUF) and (AY-GPUF), respectively, at a flow rate of 1.75 mL.min-1. Desorption of CAF has been affected by passing 500 μL of 0.05, 0.01 mol.L−1 HCl eluent onto (AY-IPUF) and (AY-GPUF), respectively. The online methods have provided satisfactory enrichment factors of 8.4 and 10.5 for (AY-IPUF) and (AY-GPUF), respectively. The time consumed for preconcentartion, elution and determination steps was 1.48 and 1.05 min, thus, the throughput was 42 and 57 h-1, for (AY-IPUF) and (AY-GPUF), respectively. The developed sorbents were studied for the determination of CAF in pharmaceutical samples which will be helpful to minimize caffeinism. Finally, in silico bioactivity, ADMET and drug-likeness predictive computational studies of caffeine were also carried out.Resumo em Inglês:
Abstract The increasing number of reports of web-based experiences on the success of Cannabis-based therapies in controlling seizures in children suffering from refractory epilepsy have led to efforts by governments and associations to a recent change in legislation. The Brazilian Health Regulatory Agency (ANVISA) allowed the import of Cannabis extracts in 2015 and the registration of the first industrialized drug in 2017. In 2019, ANVISA approved procedures for the granting of a Sanitary Authorization for manufacturing and imports, establishing marketing requirements, prescribing, dispensing, monitoring and surveillance of cannabis products for medicinal purposes. Similar to other consumer products of health concern, is necessary to ensure the quality and health safety of these products worldwide. The aim of the present study to evaluate the presence of As, Cd, Pb, Ni, Cu, Co, Cr and Mn present in Cannabis extracts and resins used in the treatment of pediatric patients with neurological diseases. Samples (48 national and 24 imported) were analyzed by Inductively Coupled Plasma Mass Spectrometry - ICP-MS. The imported extracts presented more homogeneous inorganic element values, while national extracts showed varied levels, thus indicating the highest health risk.Resumo em Inglês:
Abstract Several factors contribute to the resistance of some pathogenic microorganisms and this fact requires the search for new therapeutic alternatives. The genus Cyperus (family Cyperaceae) groups species that present chemical compounds of pharmacological interest, mainly with antimicrobial action. Thus, the present work was carried out to investigate the antimicrobial activities, antioxidants and the phytochemical profile of Cyperus articulatus L. and Cyperus iria L. Hydroalcoholic extracts (1:1, v:v) of the aerial and underground parts of these species were used to analyze the total phenol content and to evaluate the in vitro antioxidant activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl). The ethyl acetate and chloroform phases resulting from liquid-liquid partitioning of C. articulatus and C. iria extracts were evaluated in antimicrobial assays and subject to high performance liquid chromatography (HPLC-DAD) analysis. The chromatograms obtained by HPLC-DAD allowed us to identify four compounds: chlorogenic acid, catechin, quercetin, and quercitrin. The hydroalcoholic extracts of C. articulatus and C. iria showed a weak antioxidant activity with IC50 of 395.57 and 321.33 μg/mL (aerial parts), and 1,114.01 and 436.82 μg/mL (underground parts), respectively. Regarding antimicrobial activity, the chloroform phase of C. iria showed the best result at the concentration of only 31.2 µg/mL against the pathogens Candida albicans and Staphylococcus aureus. The ethyl acetate phases of the aerial parts of C. articulatus and C. iria did not show antimicrobial activity.Resumo em Inglês:
Abstract Salidroside (SAL) has been confirmed to have some protective effects against inflammatory injury. However, little information was established as to the mechanism of these protective effects. To this effect, we designed this study to explore the protective effects and mechanisms of SAL against myocardial infarction (MI). A rat MI model was established and divided into five groups (n = 6): sham, MI, MI+SAL, MI+ LY294002 (PI3K inhibitor), and MI+SAL+ LY294002. The cardiac function and histological pathology were analyzed with a color Doppler ultrasonic diagnostic instrument. Anti-oxidative enzyme activities and the production of inflammatory media were assayed by biochemical kits and ELISA. MI size and fibrosis were assayed by Masson’s trichrome staining while Bax/Bcl-2 and PI3K/Akt/Nrf2/HO-1 were assayed by Western blotting and immunofluorescence. The results showed that SAL significantly improved the left ventricle ejection fraction and fractional shortening, decreased the MI size and fibrosis, inhibited apoptosis and promoted blood vessel formation. SAL promoted anti-oxidative and anti-inflammatory abilities. Moreover, SAL enhanced PI3K/ Akt/Nrf2/HO-1 expression. To this effect, we designed this study suggested that SAL induced repair of MI via PI3K/A kt/ Nrf2/HO-1.Resumo em Inglês:
Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.Resumo em Inglês:
Abstract The present study aims to investigate the impacts of cigarette smoking (CS) and water-pipe smoking (WPS) on the visceral adiposity index (VAI), hematological characteristics, and glycemic tolerance in Iraqi healthy smokers. A total of 528 healthy males from different locations of Baghdad city were allocated to three groups; nonsmokers (176), cigarette smokers (178), and WP smokers (174). Baseline characteristics, anthropometric and hematological markers and were reported. Glycemic control was evaluated using the glucose tolerance test. The evidence of elevated VAI, disrupted hematological markers, and impaired glucose tolerance was significantly (P<0.001) different compared with non-smokers and related to the duration of smoking. The impacts of WPS seem to be significantly greater than CS in certain parameters (hemoglobin, hematocrit, methemoglobin, and 2-hour glucose tolerance values). In conclusion, CS and WPS negatively impacted body fat distribution, glucose tolerance, and hematological markers. There is a positive association between the rate of smoking and obesity, glycemic intolerance in both groups.Resumo em Inglês:
Abstract Xingnaojing (XNJ) injection was used to treat pneumonia and stroke in clinic in China, but with poor patient compliance. Xingnaojing nanoemulsion for intranasal delivery was developed to improve it. This article tried to evaluate the mucosal irritation of Xingnaojing nanoemulsion and investigate cellular uptake mechanism of its encapsulated lipophilic drugs. The toad palate model and rat nasal mucosa model were used to study the nasal ciliotoxicity and nasal mucosal irritation of nanoemulsion to evaluate its safety intranasally. The cellular uptake mechanism was studied by Calu-3 cell model. Coumarin 6 was encapsulated in nanoemulsion and the endocytic pathways were studied by cellular uptake experiments after being treated with different inhibitors. In toad palate model, the cilia movement of Xingnaojing nanoemulsion group last for 467.40 ± 39.02 min, which was obviously longer than deoxycholate group (90.60 ± 15.40 min). Studies on rats showed that the damage caused by nanemulsion is capable of being recovered. Nanoemulsion uptake was reduced obviously when cells were treated with wortmannin, and it also decreased about 13% when the temperature reduced from 37ºC to 4ºC. Mucosal irritation caused by nanoemulsion is low and the damage is recoverable. The cellular uptake of Xingnaojing nanoemulsion is energy-dependent, and macropinocytosis was the most important pathway for cellular uptake.Resumo em Inglês:
Abstract In drug therapy, it is important to provide therapeutic levels of drug to the site of action and maintain them during the treatment. This work describes the in vitro release of alendronate from sodium alginate cross-linked Montmorillonite (MMT) composite beads. Effect of crosslinking cation, concentration of montmorillonite and media on encapsulation efficiencies, and release profiles of alendronate were studied. Beads were characterized using equilibrium swelling ability study, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Energy-dispersive x-ray spectroscopy (EDX) and scanning electron microscopy (SEM). Results indicate that addition of montmorillonite increases the encapsulation efficiencies and slows down the release rates significantly.Resumo em Inglês:
Abstract Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3.Resumo em Inglês:
Abstract Vitamin D is an immune modulator, in addition to being interrelated with calcium homeostasis and bone metabolism. Recent studies have associated vitamin D with inflammatory processes. C-reactive protein (CRP), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) have been used to determine inflammation. There is no consensus on the use of these markers to determine an association between inflammation and vitamin D levels. The objective of this study was to evaluate the association between inflammatory markers and vitamin D in the elderly. A cross-sectional, descriptive study was performed based on the analysis of vitamin D, CRP (quantitative determination of C-Reactive Protein by the ultra-sensitive method) and blood count of institutionalized elderly. In this study, 64% showed vitamin D deficiency, with mean value of 22 ng/mL. In the vitamin D deficient group, the mean values found were: CRP 4.5 mg/L; NLR 2.35 and PLR 119. In the group without vitamin D deficiency the mean values were: CRP 4 mg/L; NLR 1.87 and PLR 111 without statistical difference between the values of the analyzed parameters. The results point to a predominant profile of vitamin D deficiency in the evaluated individuals. No association was found between vitamin D values and the inflammatory markers analyzed.Resumo em Inglês:
Abstract Evidence on factors associated with the progression of chronic kidney disease (CKD) is still under construction. The present study aimed to evaluate sociodemographic, clinical, and drug use factors associated with the progression of CKD. A retrospective cohort study was conducted with 193 patients with CKD stages 3A to 5- non-dialysis followed for three years in a Brazilian city. The outcome was the evolution to renal replacement therapy (RRT) or death. A total of 52.3 % (n = 101) were men and 83.4 % (n = 161) elderly. The median age was 72.0 years, and 22.3 % (n = 44) progressed to RRT or death, and the three-year mortality rate was 20.2 %. Participants exposed to angiotensin converting enzyme inhibitors or angiotensin II receptor blockers had a lower risk of progressing to the outcome (hazard ratio (HR) 0.25; p = 0.003) and higher survival (p = 0.022) when compared to those not exposed to these drugs. Age (HR 1.06;) and use of omeprazole (HR 6.25; CI; p <0.01) and hydrochlorothiazide (HR 2.80; p = 0.028) increased the risks of RRT or death. The results highlight the importance of rational management of pharmacotherapy for patients with CKD.Resumo em Inglês:
Abstract Formaldehyde is a carcinogenic compound used as preservative in cosmetic products. In this study, a derivatization procedure using MeOH, EtOH and HCl (25:25:1), and incubation at 60ºC for 4 hours was optimized, and the derivatized products - methylal, ethoxymethoxymethane (EMM), and ethylal - were directly analyzed by headspace-gas chromatography-mass spectrometry (HS-GC-MS) to determine formaldehyde concentrations. The validated method provided good linearity of the standard curve, selectivity, recovery (89.6-106.6%), repeatability, and intermediate precision (RSD < 12%), with an LOD of 0.0015% and an LOQ of 0.005% for all derivatized analytes. The validated method showed to be fast, clean, and easy to implement in a laboratory. To the best of our knowledge, this is the first reported HS-GC-MS procedure to determine formaldehyde as methylal, ethylal, and EMM as derivatized compounds. The method was satisfactorily applied for the analysis of nine hair-straightener cream samples seized by the Civil Police of the Federal District, Brazil. Eight samples contained formaldehyde, at levels ranging from 0.33 to 4.02 %, higher than the legal levels, indicating the need to control the levels of this toxic compound in cosmetic products.Resumo em Inglês:
Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.Resumo em Inglês:
Abstract The objective of the study was to evaluate the gelling properties of Dillenia indica mucilage in benzyl benzoate emulgel formulation. Mucilage was extracted from the fruits of Dillenia indica using established methods and characterized by rheology and swelling. Emulsion (F1) was prepared using the continental emulsification method. Gelling agents (2 %w /v) were prepared by dispersing in distilled water with constant stirring at a moderate speed using a magnetic stirrer. F1 was added to the gel (0-75 %w /w) to obtain emulgel formulations and evaluated using viscosity, globule size, pH, release profiles and kinetic modeling. Data were expressed as mean ± SD, and similarity factor (f2) was used to compare all formulations. Formulation viscosity was significantly higher with carbopol than with Dillenia; globule sizes increased with concentration of gelling agents, and pH reduced as the concentration of Dillenia increased. All formulations showed controlled release properties with t80 ranging between 114 and 660 min. The release was governed by Korsmeyer-Peppas model. Formulation F5 prepared with 50 % Dillenia showed highest similarity to F4 prepared with 75 %w /w carbopol. Dillenia indica demonstrated acceptable gelling properties comparable with that of carbopol and could be improved for use in emulgel formulations.Resumo em Inglês:
Abstract Adenocalymma axillarum (K.Schum.) L.G. Lohmann is a liana belonging to the family Bignoniaceae. In traditional medicine, the genus Adenocalymma is used to treat fever, skin ailments, and body, joint, and facial muscle pains, and it is also applied as cosmetic. Biological assays conducted with the A. axillarum crude leaf ethanol extract have indicated leishmanicidal activity and absence of cytotoxicity. This study aimed to analyze the A. axillarum leaf ethanol crude extract by high-performance liquid chromatography-high-resolution mass spectrometry- diode array detector (HPLC-HRMS-DAD) and to evaluate the leishmanicidal and cytotoxic activities of this crude extract, its fractions, and isolated compounds. HPLC-HRMS-DAD analysis of this extract revealed that it consisted mainly of flavonoids, with nine major compounds. Extract purification yielded 4-hydroxy-N-methylproline, 6-β-hydroxyipolamiide, quercetin-3-O-robinobioside, hyperin, isorhamnetin-3-O-robinobioside, and 3’-O-methylhyperin, which were identified by Nuclear Magnetic Resonance. The isolated compounds were inactive against Leishmania amazonensis promastigotes and human lung fibroblast cells.Resumo em Inglês:
Abstract The aims of the present study were to estimate the free-of-charge acquisition of psychotropic drugs among Brazilian adults; analyze the distribution of psychotropics according to their presence on the Relação Nacional de Medicamentos Essenciais (RENAME [National List of Essential Medicines]) and acquisition according to the source of funding (free of charge or direct payment); and estimate the proportion of free-of-charge psychotropic drugs according to therapeutic class and presence on the RENAME. This study involved the analysis of data from the 2014 National Survey on the Accessibility, Use and Promotion of the Rational Use of Medicines considering psychotropic drugs used by the adult population (≥20 years; n = 32,348). The prevalence of the acquisition of free-of-charge psychotropic drugs was 53.3% and 64.6% of these drugs were on the RENAME. Among the psychotropic drugs acquired by direct payment, 70.8% were not on the national list. Regarding free-of-charge acquisition according to the therapeutic class and presence on the RENAME, differences were found for antidepressants, anxiolytics and antipsychotics (p <0.05). In conclusion, the most used psychotropic medicines were listed in the RENAME, but free-of-charge acquisition was not provided for all of them.Resumo em Inglês:
Abstract The new coronavirus pandemic (COVID-19) is a global problem that is having severe impacts on health systems worldwide. One particular characteristic of this virus is its high transmission rate, which has led to a high demand for personal care materials such as masks, gloves, and alcohol for asepsis. Seventy percent is the ideal concentration for the ethanol used in hand sanitizers; however, this concentration can be expressed in different ways, and, consequently, the different solutions will have different antiseptic activity. In this manuscript we comment on some characteristics of alcohol-based preparations and the different ways of expressing the concentrations.Resumo em Inglês:
Abstract Acmella uliginosa, an edible herb belonging to Asteraceae family, was collected from the Terai region of Uttarakhand, India. Methanol and hexane extracts of the whole plant were prepared using soxhlet apparatus. The GC-MS analysis of plant extracts identifies 22 and 35 major compounds of methanol and hexane extracts which comprises of 74.21% and 73.20% of the total composition of extracts, respectively. The major compound in hexane was 2, 4-heptadienal (7.99%) whereas trans, trans-9, 12-octadecadienoic acid propyl ester (16.96%) was major compound in methanol extract. The extracts were evaluated for antioxidant and anti-inflammatory properties. Methanol extract showed higher free radical scavenging and reducing power activities with IC50 value 153.82±1.69 μg/mL and RP50 value of 152.28±0.41 μg/mL, respectively. The metal chelating activity was higher in hexane extract as compared to methanol extract i.e., 62.08±0.25 μg/mL. The anti-inflammatory activity assessed by its ability to inhibit denaturation was higher in methanol having IB50 value 87.33±0.15 µg/mL. The total phenolic content (TPC), total flavonoid content (TFC) and ortho-dihydric phenol content (ODP) of methanol and hexane extracts were also evaluated. TPC, TFC and ODP was higher in methanol extract having value of 122.23±0.22, 35.01±0.29 and 8±0.86 mg/mL, respectively. Acmella uliginosa, might be considered as a natural source for antioxidant and anti-inflammatory properties.Resumo em Inglês:
Abstract Colorectal cancer (CRC) one of the leading cause of cancer-related deaths worldwide. With the presently available knowledge on CRC, it is understood that the underlying is a complex process. The complexity of CRC lies in aberrant activation of several cellular signaling pathways that lead to activation and progression of CRC. In this context, recent studies have pointed towards the role of developmental pathways like; hedgehog (HH), wingless-related integration site (WNT/β-catenin) and Notch pathways that play a crucial role in maintenance and homeostasis of colon epithelium. Moreover, the deregulation of these signaling pathways has also been associated with the pathogenesis of CRC. Therefore, in the search for better therapeutic options, these pathways have emerged as potential targets. The present review attempts to highlight the role of HH, WNT/β-catenin and Notch pathways in colon carcinogenesis.Resumo em Inglês:
Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.Resumo em Inglês:
Abstract A stability indicating UPLC method has been developed and validated for the simultaneous determination of fosnetupitant and palonosetron in bulk and in injection dosage form. This combination is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeated courses of highly emetogenic chemotherapy for cancer. The chromatographic analysis was performed on an HSS, RP C18 column (2.1 x 100 mm, 1.8 µm) with an isocratic mobile phase composed of 0.25 M potassium dihydrogen orthophosphate buffer (pH 6.5), pH adjusted with dilute sodium hydroxide:acetonitrile (55:45 v/v), at a flow rate of 0.5 mL/min, and the eluents were monitored at an isosbestic point of 286 nm. The developed method was validated according to the ICH guidelines pertaining to specificity, precision, accuracy, linearity and robustness, and the stability indicating nature of the method was established by forced degradation studies. The retention times of fosnetupitant and palonosetron were observed at 1.390 and 2.404 min, respectively. The developed method proved to be accurate and precise. Linearity was established between 4.70 and 14.10 µg/mL for fosnetupitant and between 0.05 and 0.15 µg/mL for palonosetron. The LOD and LOQ were 0.115 and 0.385 µg/mL, respectively, for fosnetupitant, and 0.005 and 0.016 µg/mL, respectively, for palonosetron. Therefore, the proposed UPLC method was reliable, reproducible, precise and sensitive for the quantification of fosnetupitant and palonosetron.Resumo em Inglês:
Abstract Pharmacists acting in pharmacies and drugstores stores are some of the most accessible healthcare providers and the last to intervene before the patient takes their medicine. This puts the pharmacist in a position of authority that should be harnessed for the benefit of health. Thus, this professional is strategic for performing pharmacovigilance. Our objective of this study was to interrogate the practice of pharmacists in relation to pharmacovigilance activities, and to identify difficulties and possible stimuli for the improvement these activities in pharmacies and drugstores. The information was collected through an online questionnaire via Survey Monkey®. The data were analyzed statistically using SPSS software. Responses were received from 5174 pharmacists: mostly young women within five years of graduation and experience in pharmaceutical retail. 81% of them reported having identified suspected substandard medicines, but only 16% used the Brazilian notification system Notivisa. More than 85% of pharmacists agreed with the importance of pharmacovigilance and the recognition of reporting services as part of pharmacist duties and pharmaceutical care. The main barriers to making notifications were the lack of access and knowledge about Notivisa. Pharmacists agreed that simplifying the system would be a stimulus for notifications, and requested more feedback from notifications, as well as material and courses to understand the notification process. Pharmacists have important data to feed into pharmacovigilance systems, recognize their responsibilities and are willing to contribute, but still demonstrate low compliance. Simplification of the system and training on it are likely to increase notifications.Resumo em Inglês:
Abstract Patient’s satisfaction with healthcare services has an influence on pain management, which can be improved by patient education. Therefore, this study was aimed at identifying primary care health service opportunities in the treatment of neuropathic pain and assessing patients’ satisfaction with the provision of drug information by clinical pharmacists. This was a cross- sectional, prospective study conducted at a pain unit during March-May 2017. Patients aged >18 years; diagnosed with neuropathic pain; and who used amitriptyline, gabapentin, pregabalin, or duloxetine were included. They were verbally informed about drug treatment by a clinical pharmacist, and their satisfaction was evaluated after 1 month. In all, 90 patients were included. The median duration for which the patients experienced pain until hospital admission was 3.6 years; furthermore, this duration was longer among women (p < 0.05). However, the median time to seeking advice from doctors was 3 months. The patients (15.6%) were less likely to admit pain unit initially and 46.7% had visited different units before being admitted to a pain unit. More than 95% of the patients indicated that they had received information from a pharmacist at a clinic and were satisfied with the provision of information (median duration, 8.5 min). Thus, the involvement of pharmacists in multidisciplinary pain management may help improve health- related outcomes at hospitals and/or in community care settings.Resumo em Inglês:
Abstract Turkish Pharmaceutical Track & Trace System (ITS) is implemented as a system in which drug movements are tracked in order to ensure drug safety. The system is integrated among drug stores, pharmacies and reimbursement institutions. As the pharmacies are the primary users, their evaluations regarding the system are considered important. In this study, it was aimed to evaluate the pharmacies’- a shareholder of ITS in Turkey- satisfaction level for ITS and problems and suggestions encountered in the system. The most expressed contribution of ITS to the pharmacists’ work was the ease of medicine tracking and control with 27.1%. The average satisfaction level of pharmacists about ITS was found to be 2.9±1.2. In the research, the most expressed of the regarding the areas of ITS that need to be developed is ‘work without interruption’ with 37.1%. ITS application has provided advantages for pharmacies in many aspects that facilitate operations. However, continuous development of technology, increasing information resources and diversity, changing expectations, and utilization levels of the users require the constant improvement of the performance of the system.Resumo em Inglês:
Abstract The bidirectional relationship between tuberculosis (TB) and diabetes mellitus (DM) is a major concern for medical professionals and epidemiologists as DM affects the severity, progress and outcome of TB and vice versa. Patients affected with TB have a higher rate of morbidity, treatment failure and mortality. Likewise, DM triples the risk of contracting TB and therefore poses a threat to the progress made in the reduction of TB incidence. Hence, it is pivotal to address both the diseases keeping in mind the each other. It is known that adjunct therapy with immunomodulatory drugs can enhance TB immunity among diabetic patients. Metformin, a commonly used anti-diabetic drug with adenosine monophosphate-activated protein kinase (AMPK) activation property, has shown the capacity to reduce the growth of Mycobacterium tuberculosis within the cell. This drug inhibits the mitochondrial complex and possesses anti-inflammatory action. Therefore, Metformin can be considered as an ideal molecule for host-directed or host-targeted therapy for TB.Resumo em Inglês:
Abstract To evaluate the antibiotic susceptibility patterns in URTIs reporting to tertiary hospitals of Lahore. A cross-sectional study employing 259 culture sensitivity reports obtained from tertiary care hospitals of Lahore. Using SPSS, descriptive statistics were used to estimate frequencies and percentages. In URTIs, S. aureus (5%) was the frequent gram-positive isolate followed by MRSA (1.5%) and MSSA (1.5%), while P. aeruginosa (15.8%) was the prevalent gram-negative isolate followed by Klebsiella (13.1%) and E. coli (6.9%). Against P. aeruginosa, ceftazidime (7.7%), cefuroxime/ceftriaxone (4.6%), amoxicillin (4.3%) and ciprofloxacin (4.2%), were tested resistant, while imipenem (11.2%), ciprofloxacin (9.2%), amikacin (9.2%), meropenem/ levofloxacin/gentamicin (8.1%) and piptaz (6.9%) were found sensitive. Against Klebsiella, carbepenems (7.3%), amikacin (6.5%), ciprofloxacin (5.4%) and gentamicin (5%) were tested sensitive, whereas, ceftazidime (8.5%), ceftriaxone (5.8%), cefaclor (5.5%), ampicillin (4.6%), co-amoxiclave (4.2%) and ciftazidime/ciprofloxacin (3.8%) were found resistant. Overall, imipenem (35%), meropenem (30.8%) and amikacin (31.9%) were the three most sensitive antibiotics, while ceftazidime (25.4%), ceftriaxone (19.2%) and ampicillin (18.5%) were the three most resistant antibiotics. Data suggested that P.aeruginosa and Klebsiella, were the most frequent bacterial isolates in URTIs of Lahore. These isolates were resistant to ampicillin, cefuroxime and ceftazidime, but were sensitive to carbapenem and aminoglycosides.Resumo em Inglês:
Abstract Lysiphyllum strychnifolium (Craib) A. Schmitz. (in Thai name, Ya nang daeng) has been traditionally used to treat fever, alcohol intoxication, cancer, allergies, and blood toxins. It can be used as a health-promoting herbal tea and contains hydroalcoholic extracts. The purpose of the present study was to develop a microwave-assisted extraction method for astilbin in L. strychnifolium stems. HPLC was used to determine astilbin content. Three extraction conditions were optimized: types of solvent, microwave power levels, and the number of extraction cycles. Water:methanol (40:60) was the best solvent for astilbin extraction from L. strychnifolium stems using 450 watts and six microwave-assisted extraction cycles. This technique offers important advantages over conventional methods, such as shorter extraction times, substantial energy savings, and a reduced environmental burden.Resumo em Inglês:
Abstract Phellinus mushrooms have been traditionally used for various medicinal purposes. Protocatechuic acid, which was previously reported to be a component in some Phellinus mushrooms, has some pharmacological effects. This study aimed to validate a HPLC method for the quantitative analysis of the protocatechuic acid contents in the extracts from different Phellinus mushroom species collected in Thailand. HPLC was carried out using a C18 column and the gradient mobile phases of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Method validation was performed to assure the linearity, accuracy, precision, limit of detection and limit of quantitation of the analytical method. The linearity range of protocatechuic acid was 1 - 10 µg/ml. The average recovery was 104.16%. The method was shown to be precise with the RSD of repeatability and intermediate precision at less than 3%. The protocatechuic contents in 11 Phellinus mushrooms were in the range of less than 0.0099 - 0.4121 %w/w of the extract. The developed HPLC method was reliable and suitable for the quantitative analysis of protocatechuic acid content in Phellinus mushrooms.Resumo em Inglês:
Abstract Up to today, there is no specific treatment against SARS-CoV-2 / COVID-19 infection; there the necessity to search for alternatives that help patients with COVID-19. The objective of this study was to review the use of ozone therapy as adjunct treatment for SARS-CoV-2 / COVID-19 infection, highlighting the mechanisms of action, forms of application and current clinical evidence. A systematic review was conducted in electronic databases, searching the terminology Ozone “or” Ozone therapy “and” SARS-CoV-2 or COVID-19 or Coronavirus. Results: nineteen studies were included; ten were editorials, comments, brief reports or reviews, and nine clinical studies. We found that ozone therapy could be favorable for treating patients infected with SARS-CoV-2 / COVID-19, through a direct antiviral effect, regulation of oxidative stress, immunomodulation and improvement of oxygen metabolism. Patients who were treated with ozone therapy responded favorably; therefore, ozone therapy appears to be a promising treatment for patients infected with SARS-CoV-2 / COVID-19. Its mechanism of action justifies its use as an adjuvant therapy; however, scientific evidence is based on case series and clinical trials are necessary to corroborate its effectiveness and safety.Resumo em Inglês:
Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate.Resumo em Inglês:
Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine, demonstrating an increasing incidence every year. TongXieYaoFang (TXYF) has been used widely in China as a complementary therapy to relieve the symptoms of IBD for hundreds of years. In the present research, a network pharmacology-based approach was used to systematically explore the intrinsic mechanisms of TXYF in IBD at the molecular level. Network pharmacology-based methods, which mainly included database mining, screening of bioactive compounds, target prediction, collection of IBD-related targets, gene enrichment analysis, network construction, and molecular docking, were employed in the present study. Network analysis revealed a total of 108 potential targets derived from 22 component compounds of TXYF, among which 34 targets were common with the IBD-related targets. In the protein-protein interaction (PPI) network, 10 key targets were identified. The gene enrichment analysis suggested that anti-inflammatory processes, such as NF-kappa B signaling pathway and Toll-like receptor signaling pathway, could be the core processes involved in the action of TXYF in IBD. Molecular docking results revealed that three compounds present in TXYF exhibited strong binding affinity for PTGS2. The present study provides novel insights into the molecular mechanisms and network approaches of TXYF action in IBD from a systemic perspective. The potential targets and pathways identified in the present study would assist in further research on the clinical application of TXYF in IBD therapy.Resumo em Inglês:
Abstract The flavonoids and xanthones present in the ethanol extracts of leaves and stems of Fridericia samydoides showed that anti-dengue activities in vitro were investigated qualitatively by liquid chromatography-ultraviolet-mass spectrometry in series. Nineteen flavones and fifteen xanthones were detected and characterized on the basis of their fragmentation pattern in the positive and negative ion mode tandem mass spectrometry spectra and ultraviolet bands. Acacetin, chrysin, vitexin, isovitexin, orientin, isoorientin, mangiferin, 2’-O-trans-caffeoylmangiferin, 2’-O-trans-coumaroylmangiferin and 2’-O-trans-cinnamoylmangiferin were identified by comparison with authentic samples. The other compounds detected were tentatively assigned by analysis of the spectral data and by comparison with literature reports. In addition, it performed the fractionation of the leaves extract leading to the isolation of mangiferin, isovitexin and isoorientin. All extracts and isolated compounds inhibited the Dengue virus replication cycle with EC50 less than 25.0 µg/mL for extracts and 272.5, 85.6 and 79.3 µg/mL for mangiferin, isovitexin and isoorientin, respectively.Resumo em Inglês:
Abstract Older adults have difficulty monitoring their drug therapy in the first thirty days following hospital discharge. This transition care period may trigger hospital readmissions. The study aims to identify the factors associated with the readmission of older adults 30 days after discharge from the perspective of drug therapy. This is a cross-sectional study and hospital admission within 30 days was defined as readmission to any hospital 30 days after discharge. The complexity of the drug therapy was established by the Medication Regimen Complexity Index (MRCI).. Readmission risks were predicted by the “Readmission Risk Score - RRS”. The multivariate logistic regression was used to identify factors associated with readmission within 30 days after discharge. Two hundred fifty-five older adults were included in the study, of which 32 (12.5%) had non-elective hospital readmission. A higher number of readmissions was observed with increased RRS value, suggesting a linear gradient effect. The variables included in the final logistic regression model were the diagnosis of cancer (OR=2.9, p=0.031), pneumonia (OR=2.3, p=0.055), and High MRCI (> 16.5) following discharge (OR=1.9, p=0.119). The cancer diagnosis is positively associated with hospital readmissions of older adults within 30 days.Resumo em Inglês:
Abstract This study assessed the inhibitory potential of the probiotics Lactobacillus (LB) exopolysaccharides (EPS) with or without extracts of Satureja calamintha on enteropathogenic Escherichia coli (EPEc) responsible for gastroenteritis. Methanolic and hydromethanolic extracts were prepared by cold maceration and subjected to phytochemical screening. The compounds of the extracts were determined with the colorimetric assays and identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Antioxidant activities of the extracts were also evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging. Antibacterial effect on EPEc was evaluated by using both agar disc diffusion and microdilution methods. The in vitro test of auto-aggregation was investigated. Microbiological analysis showed that 63% of the isolated LB were producing EPS, with the amount ranging from 8.21 to 43.13 mg/L. Chemical analysis of the extracts revealed the presence of polyphenols and flavonoids, more abundant in the hydromethanolic extract, which presented the highest content with 2.11 mg EGA/g of polyphenol and 1.64 mg EC/g of flavonoids and 1.71 mg EGA/g of polyphenol and 1.15 mg EC/g of flavonoids in the methanolic extract. Hydromethanolic extracts and EPS exhibited a more important activity than did the methanolic extract against EPEc. The combined action of EPS and extracts reduced the aggregation ability of EPEc and decreased the rate of their adhesion.Resumo em Inglês:
Abstract Population aging is a worldwide occurrence that has become urgent in developing countries. Quality of life can be measured to identify functional capacity and determine the degree of impact on quality of life exerted on an individual. This study aimed to measure the quality of life of elderly people who have been living in different long-term care facilities for the elderly. Therefore, this research was developed with a qualitative and descriptive approach. Data were obtained from medical records and interviews, and were analyzed in R language interpreter software on the Ubuntu Linux operating system. Seventy-nine elderly people participated in the study. Eleven lived in Home Marista, and 68 lived in Home Jesus Maria José. A socioeconomic questionnaire was used to collect data on the socioeconomic characteristics of the participants. The Mini-Mental State Exam was used to measure degree of cognition. The Short Form-36 Questionnaire was used to measure quality of life. The present study suggests that the results found can clarify the individual vulnerability of the elderly in the age group studied regardless of the type of residence. Despite the discrepancy found regarding the care provided at the long-term care facilities, the scores, obtained with the quality of life assessment, did not show significant differences.Resumo em Inglês:
Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.Resumo em Inglês:
Abstract Sporothrix spp. are the major dimorphic fungus associated with a type of subcutaneous mycosis, sporotrichosis. The limitation of antifungal availability and the past reports of in vitro resistance of Sporothrix spp. clinical isolates makes it important to search for new compounds with antifungal activities. In this study, we therefore evaluate the in vitro activities of complexes coordinated with Co(II) and cobalt chloride hexahydrate against clinical isolates of Sporothrix spp. Broth microdilution test was performed as per M38-A2 from CLSI (2008) in duplicate for 31 clinical isolates of Sporothrix spp. (27 S. brasiliensis e 04 S. schenckii stricto sensu). The antifungal activities of the complexes coordinated with Co(II) and cobalt chloride hexahydrate were detected at a concentration range of 32-128 µg/mL for all isolates. None of the compounds demonstrated any cytotoxicity (to macrophage cells) at the concentration of 200 µg/mL. The activity against Sporothrix spp. recorded in this study instigate the continuity of experimental studies with Co(II) to search for the mechanisms of antifungal action as well as to evaluate its interaction with the commercial antifungal drugs.Resumo em Inglês:
Abstract To evaluate the prevalence of self-reported drug adherence and factors associated, as well as clinical health outcomes, for industry workers with hypertension (HTN) and diabetes mellitus (DM). This was a cross-sectional study of 137 Brazilian industry workers with HTN and/ or DM. Self-reported adherence was assessed, and the disease control was defined through blood pressure and capillary glycemia values. Data were descriptively analyzed and the factors associated with adherence were evaluated using the Poisson model with robust variance to calculate prevalence ratios. The prevalence of self-reported drug adherence was 79.6% and the prevalence of disease control was 53.8%. There was no statistically significant association between the two variables. In the controlled disease group, non-adherence was associated with being under 40 years of age, not having a partner, and having a risky alcohol consumption habit. In the uncontrolled disease group, adherence was highest for participants aged 40 years and older. The prevalence of self-reported drug adherence was high, but the prevalence of disease control was low and not associated with adherence, indicating that the self-reported adherence measure may be inaccurate. Our findings identify some factors that explain non-adherent behavior in the workforce.Resumo em Inglês:
Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.Resumo em Inglês:
Abstract Pyrostegia venusta (Ker Gawl.) Miers, popularly known as “Cipó-de São-João”, has been used in traditional medicine for its therapeutic properties. Nanotechnology is able to enhance the pharmacological activity of plant extracts. In this context, liposomes and polymeric nanoparticles containing P. venusta ethanolic extract were developed and then physico-chemically characterized to evaluate the mutagenic/antimutagenic effects of P. venusta. In addition, transaminases and serum creatinine were biochemically analyzed for liver and renal damage, respectively. The micronucleus test was performed with male Swiss mice treated orally for 15 consecutive days with free extracts and nanostructured with P. venusta, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg/kg) on the 15th day of treatment. Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. There was a significant reduction in the frequency of MNPCE (LPEPV = 183% and NPEPV = 114%, p < 0.001), indicating antimutagenic potential of the nanostructured extracts with P. venusta. The groups treated with only nanostructured extract did not show an increase in MNPCE frequency, and biochemical analyzes showed no significant difference between treatments. The liposomes and polymeric nanoparticles containing Pyrostegia venusta ethanolic extract showed biological potential in preventing the first step of carcinogenesis under the experimental conditions.Resumo em Inglês:
Abstract The present study was conducted to assess the phenolic content, and antibacterial and antioxidant activities of Lathyrus L. species. The extraction of phenolic compounds from whole seeds, seed coat and cotyledon of Lathyrus hierosolymitanus Boiss. and Lathyrus annuus L. seeds was performed employing different solvents. Total phenolic content (TPC) was measured by Folin- Ciocalteau assay, while the antioxidant activity was determined by DPPH radical scavenging activity, and reducing power assay. It was found that TPC of extracts ranged from 0.12 mg to 6.53 mg GAE/gdw. For each solvent, seed coat extracts were generally observed to render higher TPC and antioxidant activities. There was a correlation between TPC and antioxidant activity. In addition, all extracts were also examined for their antimicrobial activity against Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. Methanol extracts showed the highest antibacterial activity which is consistent with TPC, but there was no correlation between TPC and antibacterial activity. Solvents were observed to have effects on gallic acid, caffeic acid, and epicatechin extractions. HPLC analysis results of extracts confirmed methanol and ethanol as preferred solvents for phenolic extraction from Lathyrus sp. Phenolic content in the extracts could be suggested to contribute to their antioxidant and antibacterial activity.Resumo em Inglês:
Abstract The aim of this study was to determine the inductive effect of a combination of propolis and BBG extract on RUNX2 and ALP expression in the tooth extraction sockets of Cavia cobaya. Fifty- six Cavia cobaya were divided into four groups: polyethylene glycol (PEG), propolis extract + PEG, BBG + PEG, and propolis extract + BBG + PEG. The lower left incisor was extracted, and the socket subsequently filled with material according to the specific group of which the subject was a member. The subjects were sacrificed on the 14th and 30th days. Immunohistochemical staining was carried out under a light microscope at 400x magnification. Statistical analysis was then carried out by means of One-Way ANOVA and Tukey HSD tests. The mean number of RUNX2 and ALP expressions in each group was significantly different. The highest number of RUNX2 and ALP expressions occurred in the propolis + BBG + PEG group on the 30th day, while the lowest expressions were observed in the control group on the 14th day. A combination of propolis and BBG extract at a concentration of 2% of active substance effectively increases the expression of RUNX2 and ALP in preserving the tooth extraction sockets of Cavia cobaya.Resumo em Inglês:
Abstract Tetradenia riparia (Hochst.) Codd (Lamiaceae) is a species native to the African continent and used as an insect repellent. The objective of the study was to evaluate the larvicidal potential of essential oils (EOs) from the leaves, flower buds, and stem of T. riparia, collected in winter against Aedes aegypti larvae. The EOs were extracted by hydrodistillation (3 h) and identified by GC/MS. The EOs were tested against larvae of A. aegypti at concentrations ranging from 12500 to 1.5 µg/mL for 24 h. The insecticide activity was evaluated by probit analysis, and the anticholinesterase activity was determined by bioautographic method. The results of the class projection indicated sesquiterpenes as the majority class, corresponding to 60.66% (leaves), 64.70% (flower buds) and 83.99% (stem), and the bioassays on A. aegypti larvae indicated LC50 of 1590, 675 and 665 µg/mL, respectively. The anticholinesterase activity indicated that the EO of the leaves inhibited the enzyme at a concentration of 780 µg/mL, and those from the flower buds and stem inhibited up to 1560 µg/mL. The results indicated weak activity of essential oils against A. aegypti larvae.Resumo em Inglês:
Abstract Bjerkandera adusta, a globally distributed fungus, is commonly used in the nutritional practices of the East Asian population. In this study, we evaluated the nutritional composition of the lyophilized mycelium of B. adusta as well as the phenolic composition and antioxidant activity of its extracts. The mycelium exhibited moisture (7.97 %), ash (3.27 %), and fiber (5.31 %) content values similar to the established values reported in the available literature. In addition, a high protein (9.32 %) and carbohydrate (63.45 %) content was shown, with a low lipid (1.36 %) content. The energy value per 100 g sample of mycelium was 1445.85 kJ. The results obtained indicated a statistically significant variation (p < 0.05) in the phenolic composition (81.84-110.96 mg gallic acid equivalents (GAE) per g of extract), free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity (IC50 29.05-340.46 µg·mL-1), phosphomolybdenum antioxidant content (34.89-55.64 %), reduction of ferricyanide ion (66.55-69.4 %), and thiobarbituric acid reactive substance (TBARS) values (44.66-133.03 %). These results are unprecedented for this species and emphasize its nutraceutical potential.Resumo em Inglês:
Abstract Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. Dyslipidemia treatment can reduce the number of deaths caused by CVD, by decreasing the lipid profile. Evaluate the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia, regarding clinical and laboratory aspects. A quasi-experimental trial was performed in 12 months. The studied population was included patients with dyslipidemia who received a pharmacotherapeutic follow-up, which was evaluated according to the Pharmacotherapy Workup developed by the Brazilian Ministry of Health. Clinical and laboratory evaluations were performed at the baseline, after a 6 and 12-months period. The statistical analyzes were performed with the normality test of Lilliefors, Cramer Von Misses, and Anderson Darling, later the t-paired test. This study demonstrated that after 6-months of intervention, statistically significant results were verified in the reduction of LDL-cholesterol, total cholesterol, increase in HDL-cholesterol, and reduction in the blood pressure. It was observed that for high-risk patients, the achievement of targets in the lipid profile and HbA1C occurred only after 12-months, because, this population needs more aggressive targets and expressive interventions. Pharmacotherapeutic follow-up in patients with dyslipidemia reduced lipid blood levels and promoted positive clinical and laboratory outcomes.Resumo em Inglês:
Abstract The aim of this study was to identify and analyze the potential interactions between psychotropic drugs and alcohol and tobacco addiction. A cross-sectional study was carried out on secondary data collection in a Center for Psychosocial Care in Alcohol and Other Drugs. Subjects aged 18 years old and over, with alcohol and tobacco dependence, who were taking psychotherapies were included. Medical records with the most recent prescriptions were reviewed. Potential interactions between psychotropic drugs and alcohol and tobacco were analyzed using the Micromedex database and stratified according to clinical risks and mechanisms of action. The Pearson’s Chi-square test was used to find significant associations between the variables of interest. The significance level was set at 5%. Between the 2010-2018 period, 2,322 subjects were treated at the care center. Of these, 1,020 fulfilled the inclusion criteria, out of whom 515 (50.5%) were dependent on alcohol and 310 (30.4%) were dependent on tobacco. We found 1,099 potential interactions between psychotropic drugs and alcohol and 160 potential interactions between psychotropic drugs and tobacco. In relation to alcohol dependence, psychotropic drugs interacted largely with moderate clinical risk, and pharmacokinetic mechanisms of action. In relation to tobacco dependence, high clinical risk interactions and pharmacodynamic mechanisms of action predominated.Resumo em Inglês:
Abstract Schinus terebinthifolia Raddi green fruits essential oil (EO) was evaluated regarding its phytochemical profile, antimicrobial and cytotoxic activities, and toxicity. Gas chromatography with mass spectrometry was applied to identify its constituents, thereafter the minimum inhibitory concentration, minimum bactericidal and fungicidal concentrations, and its antibiofilm activity were evaluated. The EO cytotoxicity was assessed in tumor and non-tumor human cells, and in vivo toxicity was evaluated in a Galleria mellonella model. The major constituents of S. terebinthifolia EO were alpha-phellandrene and beta-phellandrene. The EO had a weak activity against all strains of Candida albicans (MIC 1000μg/mL) and had no activity against non-albicans strains, bacteria, and C. albicans biofilm. Cytostatic activity against all tumor cell lines was shown. Additionally, cell viability remained at EO concentrations up to 62.5 μg/mL. At 16 mg/mL, 50% hemolysis was observed, and it had low toxicity in vivo. Overall, the S. terebinthifolia EO was characterized by low antimicrobial and antibiofilm activities, with no evidence of toxicity to human tumor and non-tumor cells.Resumo em Inglês:
Abstract Dysmenorrhea is a common condition among females that is characterized by painful cramps before or during menstruation. It is considered as a common gynecological complaint that affects the quality of women’s life. The study evaluated prevalence of dysmenorrhea, its impact, associated risk factors, and the management strategies adopted by female university students in Taif city, Saudi Arabia. A cross-sectional study was conducted among 562 female students aged 18-30 years at the university level. The results showed a high prevalence rate of dysmenorrhea (79.4%) among the students. The most common risk factors were family history (87.4%) and length of menstruation (79%). Half (50.2%) of the respondents were absent at the university at least 1 day every month. The most widely used medications by the respondents were ibuprofen (42%) and paracetamol (40%), whereas only 3% used mefenamic acid, despite that they experienced complete pain relief with mefenamic acid. High prevalence rate of dysmenorrhea associated with risk factors such as family history and length of menstruation, was found among university students. However, pain and associated symptoms affect the quality of life.Resumo em Inglês:
Abstract Free-living amoebae of the genus Acanthamoeba are the causative agents of granulomatous encephalitis and keratitis, severe human infections. Bioactive compounds from plants are recognized as an alternative source for the development of new drugs. The Amaryllidaceae is a botanical family able to synthesize a very specific and consistent group of biologically active isoquinoline-like alkaloids. The alkaloidal fractions from the Brazilian species Hippeastrum canastrense, H. diniz-cruziae, H. puniceum, and Crinum x amabile, along with the alkaloid lycorine, were investigated against Acanthamoeba castellanii. The in vitro assays were performed with distinct concentrations of lycorine and alkaloidal fractions, while the cell viability was evaluated by the MTT method upon MDCK cells. Chlorhexidine 0.02% was used as the positive control. The effect of alkaloid fractions was concentration dependent, and 2000 μg mL-1 of H. canastrense and H. diniz-cruziae provided a 100% inhibition. At concentrations of 250, 500, and 1000 μg mL-1, the H. diniz-cruziae alkaloidal fraction showed the lowest cytotoxic effect (5%-7%) and remarkable anti-amoebic activity, demonstrating values of IC50 285.61 μg mL-1, low cytotoxicity (5%-7%), and selectivity index (7.0). Taken together, the results are indicative of the great potential that the alkaloids from H. diniz-cruziae have as new candidates for anti-amoebicidal compounds.Resumo em Inglês:
Abstract Papaveraceae is one of the prominent alkaloid-containing families, and plants of the genus Glaucium (Papaveraceae) are known for their bioactive alkaloids. Glaucium species have been used in traditional medicine in Turkey as an analgesic, narcotic, sedative, and antitussive. In this study, it was planned to evaluate the inhibitory activity of an alkaloidal extract of Glaucium corniculatum subsp. refractum on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyl oligopeptidase (POP), as well as exploring the chemical profile of the plant by using Gas Chromatography-Mass Spectrometry (GC-MS). The AChE, BuChE and POP inhibition activities of the alkaloidal extract of G. corniculatum subsp. refractum were determined spectrophotometrically. A rapid GC-MS method was used to identify alkaloids that could be responsible for these inhibition activities. In total, eleven alkaloids were identified in the alkaloid extract of the plant by GC-MS. Allocyptopine (52.92%) and protopine (25.38%) were found as the major constituents. The alkaloidal extract of G. corniculatum subsp. refractum showed potent AChE inhibitory activity (IC50:1.25 µg/mL) and BuChE inhibitory activity (IC50: 7.02 µg/mL). The extract also showed a remarkable inhibitory effect on POP with an IC50 value of 123.69 µg/mL. This study presents the first GC-MS investigation and POP inhibitory activity of G. corniculatum subsp. refractum.Resumo em Inglês:
Abstract Melatonin (MLT) reportedly reduces side effects associated with certain antineoplastic agents. Accordingly, we investigated the effect of MLT on cisplatin (CP)-induced gastric emptying (GE) delay. Mice were intraperitoneally pretreated with vehicle (ethanol 5%; control group), MLT (5, 10, or 20 mg/kg), or N-acetylcysteine (NAC; 150 mg/kg), followed by CP treatment (5 mg/kg). Pharmacological modulation was analyzed using relevant receptor antagonists (luzindole: non-selective MT1/MT2 antagonist; 5 mg/kg or 4-P-PDOT: selective MT2 antagonist; 4 mg/kg) before treatment with MLT plus CP. All treatments were performed once daily for three days. GE was assessed using phenol red. Gut morphology was examined using scanning electron microscopy and optical microscopy. Compared with the control, CP decreased GE. Pretreatment with NAC and MLT (5 and 10 mg/kg) did not prevent CP-induced gastric dysmotility; however, pretreatment with 20 mg/kg MLT prevented this effect. In addition, luzindole and 4-P-PDOT suppressed MLT-mediated gastroprotection against cytotoxic effects of CP. CP caused degeneration of the gut mucosa, which was attenuated by MLT treatment. Thus, 20 mg/kg MLT prevented the GE delay and decreased CP-induced adverse effects on the gut mucosa. In addition, the gastroprotective activity was mediated via the MT2 receptor.Resumo em Inglês:
Abstract In the present research investigation, various concentrations of hydro-alcoholic extract of Saraca asoca (Roxb.) De Wilde (family: Caesalpinaceae) dried bark and carbopol polymer at different temperature ranges were optimized for the preparation of gel formulation. Natural penetration enhancers, v.i.z., eucalyptus oil and peppermint oil were incorporated separately in the extract based gel formulations to study the rate of drug permeation across egg membrane, using franz diffusion cell. In vitro anti-arthritis potential of the formulations was also studied using inhibition of albumin denaturation, antiproteinase activity and membrane stabilization method. As per the results of current study, it is established that S. asoca dried bark hydroalcoholic extract based gel prepared using peppermint oil as penetration enhancer exhibited good permeation rate of 8.48% at the end of 3 h. The percentage inhibition of proteins by antiproteinase method at concentration of 50 µg/ml was 50.01±1.00% which was close to 53.92±0.99% as shown by the standard drug, Diclofenac. Also, the percent protein inhibition determined using membrane stabilization method was found to be 49.70±1.00%, however, it was 63.32±0.94% for the standard drug, Diclofenac. Hence, it is concluded that peppermint oil may act as a good candidate for the preparation of potent anti-rheumatic gel preparations.Resumo em Inglês:
Abstract Faced with the increase of type 2 Diabetes mellitus (DM2) and the failure in treatment, questions have been raised about the clinical situation of these patients. The present study analyzes the prevalence of hypertension and obesity in DM2 patients. Data were collected through interviews and anamnesis of 16 participants. After the meetings, in which capillary glycemia and blood pressure were measured, the participants received guidance about glycemic monitoring, blood pressure control and changes in lifestyle. Approximately 75% of the participants were women with average age of 65 years, 87.5% were sedentary, 18.75% smoked and/or used alcoholic beverages and none performed regular blood glucose monitoring. The initial blood glucose average was 148 mg/ dL and finally decreased to 133 mg/dL. There was no significant difference in blood pressure levels. Regarding the body mass index, 89.4% of the patients were above normal standards and 100% had altered waist circumference values. There is a need for studies like this in order to promote educational practices for health and disease control, highlighting the importance of multidisciplinary teams and the pharmaceutical professional, since non-adherence to blood glucose monitoring, also associated with hypertension and obesity, can interfere with the individual’s clinical condition.Resumo em Inglês:
Abstract Healthcare professionals use a variety of drug information sources to fulfill their clinical needs and medical practice. The aim of present study was to assess the sources of drug information among hospital’ prescribers and evaluate their prescribing behavior in Saudi hospitals. A cross-sectional survey was conducted among randomly selected hospital’ prescribers using a self-administered questionnaire. The response rate to the survey was 64.29%, with a ratio of 76.44% male and 23.56% female. The internet 137(60.89%) and textbooks 86(38.22%) were the prevalent sources for drug information used. Up-To-Date 107(47.56%), Medscape 105(46.67%) and FDA 74(32.88%) were the common electronic drug sources used. About 151(67.11%) of hospital’ prescribers considered the pharmacist as a reliable drug information source. The most favored drug requests by hospital’ prescribers from the pharmacists were drug alternatives 110(48.89%) followed by drug interactions 94(41.78%), side effects 78(34.67%) and indications 60(26.67%). Therapeutic efficacy 168(74.67%) and drug availability 73(32.44%) were the main factors contributed to the selection of drugs. This study shows some differences in hospital prescribers’ perceptions of sources of drug information depending upon their background and clinical practice. Therefore, knowing appropriate drug information used by hospital’ prescribers is fundamental for drug efficacy and safety in clinical practice.Resumo em Inglês:
Abstract COVID-19 (SARS-CoV-2) pandemic is raising many questions about the future of face-to-face interactions. The possible changes on healthcare delivery may provoke a long term disruption on pharmaceutical assistance requiring new approaches to provide pharmaceutical services. The proposal of pharmaceutical care is patient oriented, and its activities include different forms of interaction. The emergence of COVID-19 puts to the test all the efforts to reposition pharmaceutical care in the set of clinical activities. Now, the pharmaceutical consultations and group activities, which played a fundamental role in the reformulation of pharmacy practices, must be revised in order to reduce the risk of patient agglomeration and contamination. Several researchers suggest technology use to intermediate health care assistance. However, few studies had rigorously analyzed the effectiveness of virtual health care on the pharmaceutical field. Innovating the pharmacy workflow, during the course of a crisis like COVID-19, is the current challenge addressed to all pharmacists. This unforeseen situation requires us to reconsider our plans and actions. It will be necessary resilience, courage and creativity to achieve a consistent attitude, which provides a quick response to the health care needs in this time of crisis.Resumo em Inglês:
Abstract Liver ischemia-reperfusion (IR) injury is a major clinical trouble encountered in clinical practice. This study aimed to examine the therapeutic effects of silymarin (SM) plus glutathione (GSH) on hepatic IR injury using a rat model of liver IR. Fifty male rats were randomly divided into five groups, each consisting of 10 rats as follows: Sham, IR, SM-IR, GSH-IR and SM plus GSH-IR. All groups except sham were subjected to 30-min ischemia and 24-h reperfusion. The treated groups received 100 mg/kg of SM, GSH and a mixture of SM plus GSH, 60 min prior to the IR. After a period of 24 h, blood and liver samples were collected for biochemical and histopathological evaluations. Pretreatment with SM, GSH and SM plus GSH before hepatic IR significantly decreased IR-induced elevations of aminotransferases, and significantly reduced the histopathological damage scores of the liver in the late phase of IR injury. Moreover, SM plus GSH treatment prior to liver IR significantly suppressed inflammatory process and oxidative stress as demonstrated by attenuations in tumor necrosis factor-α, myeloperoxidase and the thiobarbituric acid-reactive substances. These findings suggest that administration of SM plus GSH prior to liver IR may protect the liver parenchyma from the effects of an IR injury.Resumo em Inglês:
Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.Resumo em Inglês:
Abstract In Brazil, medicine dispensing is a pharmacy service provided within the national health system that allows the pharmacist to interact directly with the patient in order to prevent, detect and solve problems related to pharmacotherapy and health needs. However, it is known that most dispensing services provided in the country are still limited to supplying medications and, at their finest, offering advice on medication utilization. Attempts to change this scenario present new challenges the area of pharmacy, which involve the need for a patient-centered pharmaceutical service model. This paper describes the patient-centered pharmaceutical service of high-cost medicine dispensing performed at a pharmacy linked to the Brazilian Unified Health System. In the model described here, the medicine-dispensing activity is the pharmacist’s main field of practice, which consists of identifying patient needs related to health care itself and medication utilization. It also aims to introduce the instrument developed (a Pharmaceutical Care Protocol) that contributed to implementing this clinical service provided by the pharmacist. The protocols guide and qualify the service by providing information that helps in evaluating the effectiveness and safety of treatments and in the preparation of the care plan and can be used as a basis for other services that intend to adopt clinical pharmacy practices.Resumo em Inglês:
Abstract Evaluating the effects of ecstasy on CYP2E1 activity is of great concern, mainly due to growing trends in abuse and co-administration of MDMA with ethanol and the dominant role of this isoenzyme on ethanol metabolism. This study aimed to evaluate the effects of MDMA on CYP2E1 activity. A total of 24 male rats were selected and divided into three groups. The first and second groups consisted of 12 rats and were employed to optimize the perfusion method, and the third group was employed for studying the alteration of CYP2E1 activity after liver exposure to MDMA (300 and 600 ng/ml). The amount of chlorzoxazone and 6-hydroxy chlorzoxazone in a sample obtained from liver perfusion before and after exposure to a buffer containing MDMA was determined by HPLC-FL. The enzymatic activity of rat CYP2E1 decreased after liver perfusion with a buffer containing 600 ng/ml of MDMA. However, no significant changes were observed in chlorzoxazone and 6-hydroxy chlorzoxazone concentration in perfusate before and after liver perfusion with a buffer containing 300 ng/ml of MDMA. Our findings suggest that the activity of CYP2E1 in rats might decrease only after administration of MDMA at a lethal dose. However, further animal and human studies are needed to confirm our assumption.Resumo em Inglês:
Abstract The present study deals with the computational design and analysis of a novel fusion protein based on a single chain variable fragment that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) in breast cancer cells. Alpha luffin, a small ribosome inactivating protein (RIP), was attached to the anti-HER2 antibody fragment. I-TASSER modeling provided the full-length structure of the fusion protein. Molecular docking evaluated the molecular interactions of the complementarity-determining regions of designed fusion protein to HER2. Energy minimization and molecular dynamics simulations were conducted to refine the complexes. RMSD plot revealed reasonable stability of the fusion protein during the simulation. The free binding energy profile of complexes affirmed a favorable binding affinity of proteins in complex with HER2 using molecular mechanics Poisson-Boltzmann surface area (G-MMPBSA) algorithm. In general, this approach looks promising in the development of new fusion proteins in terms of immunotoxins with appropriate cytotoxicity.Resumo em Inglês:
Abstract The purpose of this study is to optimize the composition of extragranular excipients (EGE) and mixing time of granules with EGE of paracetamol tablet formulation using Design of Experiments (DoE) approach. The effect of the composition of EGE and the mixing time of granules with EGE on granule and tableting properties of paracetamol tablet formulation was investigated using a combined model of mixture and process factors (Design-Expert 12). A total of 18 tablet formulations were manufactured by wet granulation using varying compositions of EGE and varying mixing time. Granule and tablet properties of each formulation were evaluated as response variables for the design, data generated were fitted into models and analysed to generate a design space that was used for optimization studies. The proposed EGE composition as predicted by the design was confirmed and validated after preparation and evaluation of the granule and tablet properties. The optimized composition for the EGE that yielded granules and tablets of desirable characteristics was found to be maize starch (5 %), talc (4.9 %) and magnesium stearate (0.1 %) with a mixing time of 2 min. The tablets produced with the optimized composition had better mechanical strength and disintegration time than the formulation prepared using an existing formula of maize starch (7.8 %), talc (2 %) and magnesium stearate (0.2 %) that were obtained using the One Variable at a Time (OVAT) approach. This study confirmed the relevance of quality by design in development of pharmaceutical formulations.Resumo em Inglês:
Abstract Invasive infections caused by Candida species have been strongly associated with poor prognosis and high resistance rates to some antifungals. This study aimed to identify Candida species isolated from different anatomical sites and to describe their susceptibility profile to antifungals. Ninety-four clinical isolates of Candida were obtained from a Medical Laboratory of Santa Catarina/Brazil. Species identification was performed by MALDI-TOF MS. Susceptibility assays were performed as described by Clinical Laboratory Standard Institute (CLSI) microboth method. Among the analyzed samples, C. albicans was the pathogen most incident (59.9%) followed by C. parapsilosis complex (14.9%), C. glabrata complex (8.5%), and C. tropicalis (6.3%). 37 Candida strains were isolated from vaginal content (39.3%), 21 from the nail (22.4%), 8 from tracheal aspirates (8.5%), and 7 from urine (7.4%). Together, the Candida isolates presented decreased susceptibility to azole drugs, mainly to fluconazole and itraconazole. Amphotericin B showed sensibility in 95.7% of samples analyzed. Previous knowledge about etiology and antifungal susceptibility becomes indispensable to conduct an efficient treatment.Resumo em Inglês:
Abstract The purpose of this study was to evaluate the antifibrotic and antioxidant roles of theophylline (Theo), a bioactive compound, in bleomycin (BLM)-induced pulmonary fibrosis in Wistar albino rats. Assigned into 4 groups were 32 Wistar albino rats, comprising the control group (administered 0.9% isotonic saline), BLM group (treated with BLM at a dose of 2.5 mg/kg), BLM+Theo group (treated with Theo at a dose of 75 mg/kg + BLM at a dose of 2.5 mg/kg), and Theo group (treated with Theo at a dose of 75 mg/kg). In the BLM group, a significant decrease was observed in the catalase and glutathione peroxidase enzyme activities, and reduced glutathione (GSH) (p < 0.05, p< 0.05, p< 0.001, respectively), while the malondialdehyde (MDA) levels (p< 0.001) were significantly elevated when compared to the control group. However, the MDA levels in the BLM+Theo group were also significantly higher than in the control group (p< 0.01). Similarly, the GSH levels were significantly higher in the BLM+Theo group than in the BLM group (p< 0.05). The results indicated that Theo reduced the BLM-induced activation of nuclear factor-kappaB (NF-κB) and decreased interleukin-6 (IL-6) levels, together with significant amelioration of the immunohistochemical and histopathological architecture in the lung tissues. It was concluded that the administration of Theo had a positive effect on the GSH level, and activation of NF-κB and IL-6 expression, which were significant proinflammatory markers in the BLM-treated rats.Resumo em Inglês:
Abstract In HIV-patients, the imbalance in immunological, hematological and biochemical factors can contribute to the progression to AIDS and non-AIDS comorbidities, even during combined antiretroviral therapy (cART). In this cross-sectional study, we aimed to analyze some of these parameters in 138 different asymptomatic HIV-infected patients, doing multiple comparisons between the groups, which are dichotomized in the presence / absence of cART and type of immune response (immunological responders [iR,>500cells/mL] or non-responders [iNR,<500cells/ mL]). Were analyzed cytokines and other routine laboratory parameters. Our results showed high creatine phosphokinase and low IL-10 levels in cART-patients. They also presented metabolic alterations, including elevations in total cholesterol and triglycerides, particularly in those iNR. In ART-iR an increased alanine aminotransferase was observed. Those NAÏVE-iNR presented high LDL-cholesterol, C-reactive protein and lactate dehydrogenase values. The long-term non-progressors (LTNP) showed the best laboratory results. In conclusion, many blood parameters were changed in HIV-patients, especially in those under cART. To identify LTNP individuals could be important to discussions their early therapeutic onset.Resumo em Inglês:
Abstract In order to overcome the challenges of discovering new antiprotozoal drugs, we synthesized a new class of hybrids based on S-allylCysteine Ester/Caffeic Acid Amide and evaluated four of them against Trypanosoma cruzi and Plasmodium falciparum. Hybrid 6 exhibited good activity on T. cruzi with an EC50 value of 5.45 µM, whereas hybrid 3 was active over P. falciparum with an EC50 of 18.08 µM. All hybrids displayed a good selectivity index on P. falciparum. Molecular docking computations indicated that several hybrids have good binding affinities towards the protozoa related enzymes (Cruzipain or Falcipain-2) when compared against current inhibitors. In silico studies showed that conjugates 1-3 and 6 fulfilled optimal ADME characteristics, suggesting them as safe alternatives for oral treatment of protozoal infections.Resumo em Inglês:
Abstract The treatment with hyperimmune sera constitute the only specific and effective therapy available against snakebite envenomation, most common in developing countries. Serum quality is an important factor on patient recovery time and in the incidence of death and permanent disability. To date, most sera consist of pepsin digested IgG antibodies harvested from hyperimmune animals. The use of animal derived enzymes, such as pepsin, to digest IgG, constitute a source of adventitious agents and contaminants, such as porcine circovirus. The present study aims to evaluate the use of the plant derived enzymes bromelain and ficin, as an alternative to pepsin. To this purpose, horse serum immunized against Bothrops venoms was purified with caprylic acid and digested with bromelain or ficin. SDS-PAGE results evidence the formation of F(ab)’2 fragments and suggest that a digestion time superior to 8 hours may be required to completely digest the antibodies with bromelain or ficin. F(ab)’2 fragments obtained by digestion with either bromelain or ficin digestion preserved the ability to recognize Bothrops sp. venom in western blotting assays. Therefore, both enzymes are suitable for use in large-scale production, minimizing contamination risks and increasing safety and efficiency of serotherapy treatments.Resumo em Inglês:
Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection.Resumo em Inglês:
Abstract The insertion of Pharmaceutical Care in Primary Health Care (PHC) improves patients’ clinical outcomes and quality of life. Pharmacotherapeutic follow-up can contribute to the management of chronic diseases such as diabetes, promoting better glycemic control and adherence to therapy. This study aimed to assess the Drug-therapy Problems (DTPs) and Pharmacist Interventions (PIs) on the pharmacotherapeutic management in patients with type 2 diabetes mellitus (T2DM) in a community pharmacy. A quantitative, retrospective, and cross-sectional study was conducted in a Pharmaceutical Care Program within the PHC in Juiz de Fora (Minas Gerais, Brazil). Inclusion criteria were patients with T2DM above 18, who attended at least three pharmaceutical consultations between July 2016 and October 2018 and presented two or more glycated hemoglobin tests. The study group (n = 17) was largely composed of women (65%), elderly (76%), sedentary (72%), and obese people (52%). The resolution was achieved in 79% of the DTPs identified (n = 115). Most of DTPs were related to administration and adherence to pharmacotherapy (46%). 60% of the 437 PIs involved the provision of information and counseling. In other words, accessible interventions lead to high resolvability. Therefore, clinical actuation of pharmacists could improve the prognosis in diabetes treatment.Resumo em Inglês:
Abstract Within recent past, coronavirus has shaken the whole world. The world faced a new pandemic of novel coronavirus 2019 (SARS-CoV-2/ COVID-19).It has socioeconomically impacted world population a lot in terms of education, economy as well as physical and mental health. This novel coronavirus is notorious enough that put human health at a great risk. Currently, researchers all over the world aretrying hard to develop a new drug/vaccine for its treatment. In past decades, the world population has faced various viral infectious illness outbreaks. Influenza A, Ebola, Zika, SARS and MERS viruses had whacked public health and economy. Medical science technology achieved the landmark in developing coronavirus (SARS-CoV-2) vaccines that are approved currently for emergency use. Some of the recently approved vaccines are developed by Pfizer and Moderna, Johnson and Johnson, Gam-COVID-vac (Sputnik V), Bharat Biotech (covaxin) andOxford-AstraZeneca vaccines (covishield) (Badenet al., 2021). Here, a short review is drafted focusingon infection, immune system, pathogenesis, phylogenesis, mode of transmission and impact of coronavirus on health and economy and recent developments in treating COVID-19.Resumo em Inglês:
Abstract The announcement by the WHO of the characterization of the new Coronavirus 2019 disease (COVID-19) as a pandemic, entails an adaptation by the community pharmacy in carrying out its care activity in general, with particular emphasis on ”Minor Ailments Service” in particular. The measures taken by the different health administrations in which patient telephone care by primary care offices is prioritized have left more consultations on symptoms in the community pharmacist health-related problems as pharmacies are the closest health facilities to the patient. The similarity between the symptomatology caused by the new Coronavirus with that of some Enteroviruses that cause mild respiratory and gastrointestinal tables (dry cough, fever, sore throat, vomiting, diarrhoea, etc.) makes community pharmacies highly capable places for contagion detection and prevention. A model of protocolized intervention is needed to facilitate the pharmacist’s work in discriminating during the indication between minor symptoms and symptoms of referral for possible cases of COVID-19 so that in conjunction with the rest of the staff we help control the disease and make better use of primary care consultations.Resumo em Inglês:
Abstract In this study, it was aimed to investigate the amount of antioxidant, protective properties against DNA damage and antibacterial properties against various pathogens after the interaction of Ag metal (Ag NPs/Sa) of Sophora alopecuroides L. (S. alopecuroides L) plant seed, which is grown in Iğdır and used in the treatment of many diseases. The DPPH radical quenching activity of Ag NPs/Sa was performed by using Blois method, DNA damage prevention activity by gel electrophoresis and antibacterial property by disk diffusion method. With the green synthesis method, AgNPs obtained as a result of the reaction of the plant and Ag metal are UV visible spectrophotometer (UV-vis), fourier-transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). DPPH radical quenching activity of Ag NPs/Sa was investigated in the concentration range of 25-250 μg/ml. The radical quenching activity at a concentration of 250 μg/ml was 85,215 ± 0,101%, while this value was 93,018% for the positive control BHA. It has been observed that the protective property of pBR322 plasmid DNA damage against OH radicals originating from H2O2 increases with concentration. It has been observed that Ag NPs/Sa has significant antimicrobial properties against some pathogens (B. subtilis ATCC 6633 E. coli ATCC 25952, B. cereus ATCC 10876, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212, S. aureus ATTC 29213 and C. albicans ATTC 90028) that cause disease and even some pathogens are more effective than antibiotics.Resumo em Inglês:
Abstract Insulin receptors have distributed in all brain regions, including the nucleus Accumbens (NAc), and where is implicated in the reward properties of drugs. It is well known that insulin signaling can regulate dopamine release. Therefore, in the present study, we tried to examine the effect of insulin replacement on the acquisition and expression of morphine-induced conditioned place preference (CPP) in diabetic rats. Forty-eight male Wistar rats were divided into two non-diabetic (Naïve) and diabetic groups rendered by a single injection of streptozotocin (STZ). These groups separately received insulin (10U/kg) or saline (1 ml/kg) one hour prior to morphine administration (5mg/kg;s.c.) during conditioning days (acquisition phase) or post-conditioning day (expression phase) in the CPP paradigm. In this paradigm, conditioning score (CS) and locomotion activity were recorded by Ethovision. The STZ-induced diabetic rats displayed higher CS compared to naïve rats (P<0.05). This effect was abolished in all diabetic rats that received insulin during conditioning days but not the expression phase. This study has provided evidence that insulin plays a modulatory role in morphine-induced CPP, and insulin replacement during the acquisition phase could reduce the rewarding properties of morphine in diabetes conditions through a possible modulating effect on dopamine release in the NAc region.Resumo em Inglês:
Abstract A cationic liposomal gene delivery system comprising DOTAP, DOPE, and cholesterol was prepared and optimized. The results showed that the liposome/DNA (LP/DNA) system had spherical morphology, with a particle size of around 150 nm and zeta potential of approximately 30 mV. Cytotoxicity experiments showed that cells treated with all of the liposome carriers- with the exception of LP1-had more than 80% viability even at a weight ratio of 30. The in vitro transfection efficiency was measured using a Promega™ Luciferase Assay System. Of the tested lipoplexes, LP2/DNA showed the highest cell transfection efficiency (at a weight ratio of 10)-which was similar to or slightly lower than that of Lipofectamine® 2000 in HeLa, A549, and SPC-A1 cell lines. After freeze-drying, the cell transfection efficiency decreased slightly (P>0.05). The cell uptake mechanism study showed that LP/DNA lipoplexes mainly entered cells via clathrin-mediated and caveolin-mediated endocytic pathways. The results confirmed that LP2 has potential for use as an effective gene carrier, and provides experimental evidence to support its further development as a safe and effective gene delivery system.Resumo em Inglês:
Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.Resumo em Inglês:
Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus.Resumo em Inglês:
Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient’s safety.Resumo em Inglês:
Abstract Solanum dolichosepalum is a plant with anti-infective effects. It is a healing agent and has ethnopharmacological uses. In this study, the antifungal activity of extracts and fractions of this species on C. albicans and F. oxysporum was evaluated. The antioxidant activity was measured using the ABTS and DPPH methods, and by determining the total content of phenolic compounds. An HPLC-DAD qualitative analysis was carried out to identify phenolic compounds and alkaloids. Pearson’s correlation coefficients were calculated. Inhibitory effects were found in all the extracts and fractions on the analyzed microorganisms. F. oxysporum was the microorganism most sensitive to the action of S. dolichosepalum extracts. All extracts and fractions showed antioxidant activity, with the acetone extract and the acetone fraction being those that generated the best results. The content of total phenolic compounds showed that acetone has a greater affinity with the phenolic compounds present in S. dolichosepalum. In this plant, p-Hydroxybenzoic, vanillic, ferulic, trans-cinnamic, caffeic, p-coumaric, and rosmarinic acids were found, as well as theobromine, quercetin, and luteolin. The content of total phenolic compounds was determined to be directly proportional to the inhibition of the ABTS and DPPH radicals, and the inhibition of the analyzed microorganisms. It was determined that the extracts and fractions obtained from S. dolichosepalum show antioxidant and antifungal activity.Resumo em Inglês:
Abstract To identify and characterize the most frequent Drug Interaction (DI) in a Jundiaí Hospital. Exploratory, descriptive, and analytical cross-sectional study with a quantitative approach. The source of the study is 100 prescriptions made by the medical service of a hospital in Jundiaí, dispensed from August to October 2018, by the pharmacy of the mentioned hospital for palliative care, mental health, and emergency care. Data plotting in Excel. Of the 100 prescriptions analyzed 60 had at least one type of interaction, 164 DI were found, 14.6% severe, 67.7% moderate, 17.1% minor and 0.6% unspecified. The mechanism of interaction that most appeared in the study was pharmacodynamics, 54.3%, pharmacokinetics were present in 34.1% of DI and 11.6% were not specified. The group most affected by DI was male 33% of prescriptions, female 27%, and 40% showed no interactions. The age group with the most interactions was from 50 to 59 years old. Of the prescriptions that had MI, those with 4 or more interactions were the ones that prevailed. The class of drugs that presented the most interactions was psychotropic drugs. A relevant frequency of interactions was identified by the present study, being the class of psychotropic drugs the most evident and interactions of medium severity the most found, which may be responsible for lowering the clinical condition of patients and the need of possible additional interventions. The data presented may contribute as epidemiological indicators, guiding corrective actions, aiming at the welfare of patients.Resumo em Inglês:
Abstract The objective of this study was to evaluate the influence of vitamin C (VC) on the stability of stored liposomes under different climatic conditions. Liposomal formulations containing 1 mg/mL of VC (LIP-VC) and blank formulations (LIP-B) were prepared by the reverse-phase evaporation method. After preparation, they were characterized according to their refractive index, average vesicle diameter, polydispersity index (PDI), zeta potential, pH, content, encapsulation efficiency (EE%), morphology, stability and antioxidant activity. For stability, LIP-VC and LIP-B were stored in different climatic conditions (4 °C, 25 °C and 40 °C) for 30 days. The LIP-VC presented 1.3365 refractive index, 161 nm of mean diameter, 0.231 PDI, -7.3 mV zeta potential, 3.2 pH, 19.4% EE%, spherical morphology, 1 mg/mL of VC content, and antioxidant activity of 12 and 11.4 μmol of TE/mL for the radical DPPH and ABTS+, respectively. During stability, the LIP-B stored in 40 °C showed an instability in the parameters: PDI, vesicle size and zeta potential after 15 days, while the LIP-VC remained stable in its size and PDI for 30 days. After that, it is shown that VC can be used as an antioxidant and stabilizer in liposomes to increase the stability and shelf-life of vesicles.Resumo em Inglês:
Abstract The composition and pharmacological properties of Lippia alba (Mill.) (L. alba) (Verbenaceae) flower and leaf essential oils (EO) were determined in this study. The major constituents in the flower EO were geranial (49.83%) and neral (32.75%), and in the leaf EO were geranial (38.06%), neral (31.02%), and limonene (18.03%). Flower EO inhibited thrombolysis induced by Bothrops moojeni (B. moojeni) and Lachesis muta muta (L. muta muta) venoms (0.05-1.2 µL mL-1). When tested against L. muta muta venom, the protective effect was smaller in both EO. The EOs prolonged the clotting time induced by L. muta muta venom and a procoagulant effect was observed on B. moojeni. In the comet assay, the flower EO presented anti-genotoxic action (damage frequency of only 11.6 - 34.9%) against the L. muta muta venom. The positive control (Doxorubicin) and the venom alone presented a damage frequency of 80.3% and 70.7%, respectively. The flower EO protected DNA from damage induced by L. muta muta venom. L. alba leaf and flower EOs presented anti-genotoxic action.Resumo em Inglês:
Abstract The main aim of the paper is to assess whether vitamin C, vitamin D, and natural honey can be administered in the course of the COVID-19 pandemic for promising in line methods with recent evidence. Both systematic literature and clinical trial identification were conducted by searching various databases. A total 58 articles and 29 clinical trials were selected wherein 11 for vitamin C, 16 for vitamin D, and 2 for natural honey were identified for analysis. The high doses of vitamin C (i.e. ‘200 mg/kg body weight/day, divided into 4 doses’) has been found to reduce COVID-19 lung damage, various flu infections. Additionally, the high doses of vitamin C can shorten around 7.8% stay in the intensive care unit. At the same time, vitamin D can effectively protect from lung injury and acute respiratory infections whereas vitamin D deficiency severely affects 75% of the institutionalized people (serum 25(OH) D < 25 nmol/L). Meanwhile, natural honey which contains proteins (0.1-0.4%); ash (0.2%); water (15-17%) has potential antiviral effects and the ability to improve immunity. Therefore, the administration of vitamins and honey is the promising evidence-based approach for reducing fatalities, saving lives, and bringing the COVID-19 pandemic to a rapid end. It is believed that the utilization of vitamin C, vitamin D, and natural honey with the current treatment may be effective in treating COVID-19-caused fatal complications such as pneumonia. Therefore, high-level clinical studies are required on COVID-19 to administrate the effects of vitamins and natural honey.Resumo em Inglês:
Abstract Streptococcus agalactiae (group B Streptococcus, GBS) remains one major neonatal pathogen, being maternal colonization a risk factor for infection development. Despite effective, the usage of antibiotics to prevent neonatal infections has limitations. The bacterial polysaccharide capsule is a virulence determinant, a target for vaccine directed to pregnant women, and also the most useful epidemiological marker of GBS infections. Capsular polysaccharides are diverse and disease severity varies according to the expressed type. Here, capsular typing of 124 GBS isolates recovered from pregnant women was determined by a multiplex PCR-based method. The most frequent types were Ia (33.0%), II (25.8%) and V (21.8%). Other types found were Ib (8.9%), III (8.9%) and IV (1.6%). While type Ia was prevalent during the whole period (2002-2018), fluctuations in distribution of other types, specially V, were observed over time. Capsular type III, traditionally associated with severe neonatal infections, was poorly detected. Distribution of maternal GBS capsular types in the metropolitan area of Rio de Janeiro, with prevalence of Ia and II, is quite different from other parts of the world. The knowledge about GBS capsular type distribution is essential to predict the theoretical impact of developing capsule-based vaccines in the local population.Resumo em Inglês:
Abstract Trace elements have an important influence on the living system and play a major role in a variety of processes necessary for life. This case study was conducted as an attempt to expand our knowledge of the relationship between trace elements and their effect on acute pancreatitis. Sixty-five patients diagnosed with acute pancreatitis with mean age 43.6 years, along with sixty-five healthy volunteers with a mean age 45.7 years, were included in this study. The obtained results indicated a significant increase in the Cu, Ni and Cr levels, and a significant decrease in the Zn, Mg and Fe levels for acute pancreatitis patients compared with the control group (p <0.001). In addition, a remarkable increase in the Cu/Zn ratio was observed in patients. The current work provides important evidence of correlation between changes in copper and zinc levels and the risk of acute pancreatitis. Also, an increased Cu/Zn ratio may be a useful indication for the diagnosis and monitoring of acute pancreatitis. Moreover, the current study concluded that there is a possible relationship of Mg, Fe, Ni and Cr with acute pancreatitis. Thus, it can be suggested that these elements are reliable to provide indications for warning of the risk of acute pancreatitis.Resumo em Inglês:
Abstract Diabetic mellitus is an emerging disease in Saudi Arabia. In this regard, a cross-sectional retrospective study was conducted to evaluate drug utilization pattern and the cost associated with non-insulin-dependent diabetes mellitus disease management in Saudi Arabia. Data retrieved from the electronic pharmacy records during the last one year were employed in this study. World Health Organization (WHO) Defined Daily Dose (DDD) method was employed to compute the daily price of each oral hypoglycaemic agent. The American Diabetes Association (ADA) guidelines and protocols were used to evaluate the level of adherence. A total of 17057 patients were enrolled in the study. Out of the 17057 patients enrolled in the study, 60.06 % (10246) were males and the rest females. In monotherapy, biguanides (metformin) were the most recommended and utilised drugs among 5673 patients (33.25%). The most commonly used drug combination was found to be sitagliptin+metformin (1754 units). The cost per unit dose was highest for liraglutide (A10BJ02) 258.32SR (68.79USD), and lowest for metformin (A10BA02) 0.49SR (0.13 USD). Metformin was the choice drug for the diabetes patients; biguanides (metformin) and DPP-4 (sitagliptins) were the most familiar established dose combination employed. Generic drugs should be used in order to reduce overall cost.Resumo em Inglês:
Abstract The effectiveness of sun protection depends directly on the photo-protective product employed, the way it is used and the amount applied. Many studies report that sunscreens are often applied incorrectly, at amounts much lower than those recommended for the sun protection factor (SPF) specified on the label. When not used properly, the effectiveness of the product against sun exposure damage is reduced. Currently, sunscreens are available in a variety of different formulations and types, such as stick (bar), aerosol, cream, lotion, oil, tanning formulations and makeup. However, developing an effective stable photo-protective formula that can be correctly applied regardless of type poses a challenge, as effectiveness is dependent on several factors. Factors influencing effectiveness include sun exposure conditions (direct or indirect), level of protection (SPF), amount of product applied, maximum exposure period before reapplication, product type (spray, lotion, etc.), layer thickness required, coverage, and ability to spread and permeate into the skin. Studies comparing the effectiveness of different forms of sunscreens, the amount of product applied by consumers and SPF and UVA protection determined by validated methodologies, are lacking. Therefore, the objective of this study was to review the available literature on the topic and discuss the effectiveness of sunscreen formulations and factors influencing sun protection. This review was carried out on the scientific databases MEDLINE, PubMed and Scielo. Of the many publications retrieved, thirty-nine articles most relevant for this review were selected.Resumo em Inglês:
Abstract This study aimed to investigate the acute effects of oleic acid (OA) on glucose homeostasis in mice fed a standard chow diet (SCD) and a high-fructose, high-fat diet (HFrHFD); moreover, the role of free fatty acid receptor 1 (FFAR1) was evaluated. The mice in the two groups were further divided into three subgroups as follows: control, OA (40 mg/kg), and OA + GW1100 (0.4 mg/kg, selective FFAR1 blocker). After a 16-week feeding period, the mice received the drugs via intraperitoneal (i.p.) injection followed by an i.p. glucose tolerance test (IPGTT) 30 min later. After 3 days, the mice received the same drugs to examine the effects of the drugs on the hepatic levels of phosphatidylinositol-4,5-bisphosphate (PIP2) and diacylglycerol (DAG). OA in the SCD-fed mice significantly increased the blood glucose level (48%, P < 0.001) after 30 min of glucose load compared to that in the control group, but did not affect the levels of PIP2 and DAG. Pre-injection with GW1100 significantly decreased the area under the curve of the IPGTT (28%, P < 0.05) in the SCD group compared to that in the SCD + OA group. OA reduced the blood glucose level (35%, P < 0.001) after 120 min of glucose load in the HFrHFD-fed mice; in addition, it increased hepatic PIP2 (160%, P < 0.01) and decreased hepatic DAG (60%, P < 0.001) levels. Pre-injection with GW1100 blocked the effects of OA on hepatic PIP2 and DAG without affecting the glucose tolerance. In conclusion, OA acutely impaired the glucose tolerance in the SCD-fed mice by acting on FFAR1 but did not improve it in the HFrHFD-fed mice.Resumo em Inglês:
Abstract The acid dissociation constant of drug active compounds (arylpropionic and aryl acetic acids) were determined in acetonitrile and water binary mixtures (corresponding volume fractions of 0.40, 0.45, 0.50, and 0.55) by using a multi-wavelength spectrophotometric method. Drug active compounds, which were slightly soluble in water, were studied in these binary mixtures. The dissociation constants of drug active compounds are important in drug design studies and in any research of the biopharmaceutical and physicochemical properties of drugs. The STAR program was used for the determination of dissociation constants. The acidity constants of arylpropionic and aryl acetic acids were correlated with the Kamlet and Taft solvaatochromic parameters. Aqueous pKa values of these arylpropionic and aryl acetic acids were determined from pKa values obtained from acetonitrile and water binary mixtures with varying volume fractions. The studied drugs had a pKa value corresponding to base functional group. Results showed that the acid dissociation constant values of the drug active compounds increased with an increase in acetonitrile content in the medium.Resumo em Inglês:
Abstract Recently, the world has coped with the challenge of the novel SARS-CoV-2 rapid spreading, causing COVID-19. This scenario has overburdened health systems, forced social isolation, and interrupted some services, changing the way how health assistance is provided. The management of chronic infectious diseases such as tuberculosis is a sensitive matter in times when the control strategies are at risk. In this sense, how could a high burden disease such as tuberculosis affect or be affected when combined with the COVID-19 pandemic? Patients with tuberculosis have a social background and lung impairment that represent risks in the pandemic scenario of another widely transmitted respiratory disease. Thus, even with several questions remaining unanswered, research and public policies should be addressed to control the effects of the current highly contagious COVID-19 without forgetting how it will affect the natural progression of patients suffering from tuberculosis.Resumo em Inglês:
Abstract The monoterpene 4-carvomenthenol (Carvo) is found in essential oils of plant. Here, we evaluate the Carvo oral pretreatment in acute inflammatory experimental models and in silico molecular docking. Mice pretreated with Carvo were challenged and submitted to the protocols: paw edema, peritonitis, scratching behavior and anaphylactic shock reaction. Besides, we used histamine H1 receptor, cyclooxygenases (COX-1 and COX-2) and phospholipase A2, as targets for molecular docking analysis. Carvo inhibited the carrageenan-induced paw edema and decreased the peritoneal influx of polymorphonuclear cells on carrageenan-challenged mice without interfering with the mononuclear cell influx. Moreover, Carvo diminished the histamine, PGE2 and compound 48/80 induced paw edematogenic effect. The monoterpene also diminished the mice scratching behavior and, surprisingly, avoided the animal death caused by compound 48/80 in 30 min. Through the docking analysis, Carvo showed favorable binding energy to the histamine H1 receptor. This study demonstrates that Carvo attenuated the allergic inflammatory process, decreasing edema, cell migration, activation of mast cells and the histamine release, probably due to interaction of Carvo with the histamine H1 receptor, ameliorating the itching and the anaphylactic shock reaction. Therefore, the results of this study indicate that Carvo has anti-inflammatory properties by reducing the histamine effects.Resumo em Inglês:
Abstract In pediatrics, drug therapy is commonly performed through adaptations of the dosage forms to adult use, increasing the risk of adverse drug reactions. In this context, studies assessing the severity and avoidability of the adverse reactions in children, especially those caused by antimicrobials, are still scarce. This work aimed to investigate suspected antimicrobial adverse reactions (ATM-ADRs) in pediatric patients admitted to a public hospital in northeastern Brazil, focusing on causality and avoidability analysis. A cohort study was carried out over a period of six months in a 64-bed pediatric unit. The incidence of suspected adverse reactions caused by antimicrobials was 14.65%. Most reactions were rated as probable (89.13%), with moderate severity (84.78%) and possibly avoidable (45.65%). The analysis indicated that the use of a larger number of medications (p<0.0001) and longer hospital stay (p=0.004) were related to the occurrence of ATM-ADR. Our findings demonstrated that almost half of the suspected reactions could be prevented and that the antimicrobial’s clinical management is relevant in this context. Besides, increasingly accurate adverse reaction classification instruments are essential. These results can support the development of therapeutic guidelines addressed to a safe and effective pharmacotherapy in the pediatric area.Resumo em Inglês:
Abstract The COVID-19 pandemic puts the healthcare systems at risk due to the still uncertain operational and financial impacts of it. The difficult economic conditions of the population also call for more attention from government officials to define strategies that guarantee access to health services and products. Maintaining the supply chain of pharmaceutical products is not only paramount to cover the immediate medical response but will be fundamental to reducing disruption of the healthcare system. Increasing drug prices during the pandemic is definitely not a strategy that contributes to access. In this sense, this commentary presents a criticism of a decision by the Brazilian government that may impact the availability in health services and the population’s access to medicines necessary for the maintenance of life.Resumo em Inglês:
Abstract Biopharmaceuticals, mainly monoclonal antibodies, and fusion proteins are drugs that have gained notoriety in the treatment of various chronic and inflammatory diseases and have high prices. The study aimed to verify which monoclonal antibodies and fusion proteins were most incorporated into the Unified Health System (SUS), which therapeutic indication most benefited from them and to analyze public spending on these biopharmaceuticals from January 2012 to September 2019. This study performed a qualitative and quantitative analysis of biopharmaceuticals incorporated by SUS. The data were collected on the websites of CONITEC and the Health Price Bank. The results demonstrated that subcutaneous adalimumab was most frequently incorporated, and the most requested therapeutic indication was rheumatoid arthritis. Public spending on biopharmaceuticals exceeded R$ 28 billion (more than US$ 140 billion). However, a downward trend was confirmed (-266.7%) in the period evaluated. Despite the increase in demand and public spending on biologics in general, in Brazil and worldwide, the results of this research show that there was a drop in public spending on the biopharmaceuticals studied in the last seven years.Resumo em Inglês:
Abstract The main aim of transdermal drug delivery (TDD) is to deliver a specific dose of drug across the skin and to reach systemic circulation at a controlled rate. On the other hand skin is the target for topical drug delivery. Mentioned drug delivery systems (DDS) have numerous advantages compared to oral and parenteral routes. Avoidance of first-pass metabolism, prevent drug degradation due to harsh environment of the stomach, allow controlled drug delivery, provide patient compliance, and pain-free administration are a few of them. To achieve all of them, a DDS with suitable polymer is the primary requisite. Based on the recent trends, natural polymers have been more popular in comparison to synthetic polymers because the former possesses favourable properties including nontoxic, biodegradable, biocompatible, low cost, sustainable and renewable resources. In this context polysaccharides, composed of chains of monosaccharides bound together by glycosidic bonds, have been successfully employed to augment drug delivery into and across the skin with various formulations such as gel, membrane, patches, nanoparticles, nanofibres, nanocomposite, and microneedles. In this chapter, various polysaccharides such as cellulose, chitosan, and their semisynthetic derivatives, alginate, pectin, carrageenan etc, were discussed with their diverse topical and TDD applications. In addition, various formulations based on polysaccharides and limitations of polysaccharides were also briefly discussed.Resumo em Inglês:
Abstract Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.Resumo em Inglês:
Abstract Intrauterine adhesions cause several gynecological problems. Althaea officinalis L. roots known as marshmallows contain polysaccharides (M.P.) which possess anti-inflammatory and anti-ulcerogenic activities also can form a bio-adhesive layer on damaged epithelial membranes prompting healing processes. Vaginal formulations of herbal origin are commonly applied to relieve cervico-uterine inflammation. Herein, we aim to develop and evaluate vaginal suppositories containing polysaccharides isolated from the A. officinalis root. Six formulations (four P.E.G.-based and two lipid-based suppositories containing 25% and 50% M.P.) met standard requirements, which were then subjected to qualitative and quantitative evaluation. All suppositories exhibited acceptable weights, hardness, content uniformity, melting point, and disintegration time, which fall within the acceptable recommended limits. Higher concentrations of M.P. in PEG-bases moderately increased the hardness (p<0.05). PEG-formulations showed content uniformity>90% of the average content while it was 75-83% for suppocire formulations. All formulations disintegrated in<30minutes. In-vitro release test revealed that M.P. release from 25%-MP formulations was higher than that of 50%-M.P. suppositories. Overall, results revealed the feasibility of preparing P.E.G.-or lipid-based suppositories containing M.P., which met the B.P. quality requirement.Resumo em Inglês:
Abstract Testicular damage is one of the most hazardous effects of chemotherapy as it is frequently associated with oligozoospermia and azoospermia. This study aimed at evaluating the protective effect of melatonin in a rat model of busulfan-induced testicular injury. Rats were divided into four groups: control, melatonin, busulfan, busulfan plus melatonin. After 15 days, the semen was collected from the epididymis and testes were assessed. Sperm removed from cauda epididymis and analyzed for sperm count and viability. Testis tissues were also removed, fixed in formalin and were embedded in paraffin. Sections of testis tissue were stained with hematoxylin-eosin for histological examination and prepared for TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay to detect apoptosis and PCNA (proliferating cell nuclear antigenassay) to detect proliferation cells. Serum and testes supernatants were separated to detect testosteron level and oxidative stress parameters. In histological examination, degenerative changes in seminiferous tubules were observed in the experimental groups. In biochemical examination, the total oxidant status (TOS) levels in Busulfan group were significantly higher than in the control group while the total antioxidant status (TAS) levels of all the groups were similar. In conclusion, the beneficial properties of melatonin treatment by its potent anti-oxidants may reduce adverse effects of chemotherapy in the reproductive system in a rodent system.Resumo em Inglês:
Abstract Pharmaceutical Care is a subject within the Pharmacy Degree that is taught using theoretical and practical classes. When COVID-19 appeared, Faculty of Pharmacy had to change its way of teaching and learning to online classes. Our aim is to assess the impact of COVID-19 situation on practical classes in Pharmaceutical Care. A prospective study was performed by undergraduate students from Pharmaceutical Care subject. Students attended to 2-day practical classes and were assessed through an evaluative workbook. Undergraduate students (n=390) obtained a score of 8.4±0.8 in practical classes, being higher in face-to-face sessions than online sessions, but not significant differences among both methodologies. The higher score was for the session of minor ailment services (9.3±1.3) and the lower for Personalized Medication Dosage (7.0±1.6) and similar in both scenarios. 59% of students obtained more than 8 score in the global punctuation, being higher in in-face-to-face practical classes. This study showed that learning in health care can be guided and evaluated through an online method. Adapt to new technologies, prevent vulnerable students from being left behind, as well as working on cross-cutting skills at a distance, are some of the challenges of higher education in times of COVID-19.Resumo em Inglês:
Abstract Serrapeptase, a proteolytic enzyme, has been used for the adjuvant treatment of many diseases. However, its fibrinolytic activity is still uncertain. Herein, the fibrinolytic activity of serrapeptase and its in vitro thrombolytic effects were investigated. The results showed that the fibrinolytic activity of serrapeptase was 1295 U/mg, and the specific activity was 3867 U/mg of protein when its proteolytic activity toward casein was 2800 U/mg. The optimum temperature and pH for serrapeptase activity were 37-40°C and 9.0, respectively. At 1 mmol/L, Zn2+, Mn2+ and Fe2+ could activate the fibrinolytic activity of serrapeptase, while K+, Cu2+, sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA) inhibited it. In vitro tests showed that serrapeptase could completely prevent blood coagulation at 150 U/mL, and the percentage of blood clot lysis reached 96.6% at 37°C after 4 h at 300 U/mL. These results indicate that serrapeptase has excellent fibrinolytic activity, and can be used as a health food or candidate drug for the prevention or treatment of thrombotic diseases.Resumo em Inglês:
Abstract This study was aimed to explore the chemical composition and biological activities of essential oil from aerial part of Mosla dianthera along with its major isolated compound, carvone. The hydro-distilled essential oil was analysed by GC-MS and biological activities were investigated in terms of antioxidant, anti-inflammatory, herbicidal, antibacterial, anti-fungal and anti-feedant properties. GC-MS analysis led to the identification of forty-nine components contributing 96.2% of essential oil with carvone (41.9%) as the most abundant constituent. The oil and carvone showed good to moderate antioxidant potentials determined by radical scavenging, reducing power and metal chelating activities. Carvone showed good anti-inflammatory activity (78.0%) compared to essential oil (74.2%). Both essential oil and carvone exhibited excellent herbicidal activity against Raphanus raphanistrum subsp. sativus seeds. The essential oil and carvone showed significant anti-bacterial efficacy against Bacillus cereus and Escherichia coli. It was observed that essential oil showed strong antifungal property than carvone against Alternaria alternata and Curvularia lunata. Both the samples exhibited anti-feedant activity in a dose dependent manner against third instar larvae of Spilosoma obliqua. Results obtained revealed the possible applications of essential oil and carvone as a bioactive source of natural antioxidants, excellent herbicide and an effective substance for antifungal and antifeedant activities.Resumo em Inglês:
Abstract Curcumin is a plant-derived compound with polypharmacological properties that are hampered by its poor solubility, fast degradation, etc. Wound closure complications that follow tooth extraction are numerous, and relatively frequently additional treatment is needed to prevent unwanted process chronification. The present study aims to compare the effects of free and the nanoliposome-encapsulated curcumin on tooth extraction wound closure. The experiments were performed on Wistar rats where both forms of curcumin were applied topically on a tooth extraction wound for seven days. Changes in tissue oxidative stress (malondialdehyde and oxidized proteins concentrations, and catalase activity) and inflammation (nitric oxide levels and myeloperoxidase activity) related parameters were studied three and seven days following the tooth extraction. Also, the extent of pathohistological changes and osteopontin immunohistochemical expression were studied. The obtained results indicate that both forms of curcumin prevent an increase in oxidative stress and inflammation-related parameters in the studied samples at 3-and 7-day time points. Additionally, we found that curcumin diminished tissue inflammatory response and osteopontin expression, while at the same time it caused faster granulation tissue maturation. The encapsulation of curcumin in nanoliposomes proved to be better in improving the extraction wound healing process than the free curcumin, giving this formulation a potential in the pharmaceutical industry.Resumo em Inglês:
Abstract The objective of the study was to develop an easy, cheap, effective, and safe, small-scale method for sample preparation suitable for the simultaneous high-performance liquid chromatography (HPLC)-ultraviolet (UV) assay of capecitabine and its 5′-deoxy-5-fluorocytidine (5′-DFCR) metabolite in mouse blood plasma. The suitability of the proposed method of sample preparation was verified by the optimal effectiveness and efficiency achieved in the overall analytical workflow. The chromatographic separation of capecitabine and its first metabolite was performed on a Hypersil GOLD aQ column with a mobile phase consisting of 1% formic acid, methanol, and water, and run in a gradient elution mode. The absence of interfering endogenous components at the retention times of each analyte was confirmed by the chromatographic analysis of blank matrices and matrices spiked with the corresponding standards. The absence of any tactile matrix effect was also recorded. For the first time, the effect of the vacutainer’s anticoagulant on the extraction efficiency of both analytes was evaluated. The method was found to be accurate, precise, and specific. The estimated mean “extraction” efficiencies were ≥90% for each analyte. The lower limit of quantitation for both capecitabine and 5′-DFCR was 0.05 μg/mL.Resumo em Inglês:
Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine.Resumo em Inglês:
Abstract Flavonoids are a diverse class of polyphenolic substances largely found in plants including citrus peels and are reported to posess a variety of biological activities. We investigated important flavonoids apigenin, hesperidin, narigin, quercetin and tangeritine against diabetes and associated conditions. In current project drug likeness, ADMET analysis, molecular docking and in vitro assays were performed. The apigenin, quercetin and tanagretin exhibited compliance with Lipinski’s rule of five. The molecular docking analysis showed best fit in transcriptional regulator 3TOP and 1IK3 in all tested compounds. During antioxidant assays, all flavonoids presented excellent activities. In the α-glucosidase assay, quercetin showed highest inhibition (76% at final concentration of 52 µg/ml) followed by tangeritin (73% at final concentration of 52 µg/ml). In case of 15-Lox assay, highest inhibition was seen in case of quercetin (75%) followed by apigenin (53%). In the AGEs assay, the quercetin showed 47% inhbition of protein cross link formation preceeded by the tenegretin exhited 37% inhibition. It was therefore concluded that tested flavonoids have significant activities in both in silico and in vitro models that is mainly due to differences in structural features and polar surface area.Resumo em Inglês:
Abstract The present study aims to examine the anti-diabetic effects of fullerene C60 nanoparticle, as an anti-oxidant compound, on serum glucose level, body weight, food and water intake, and pancreatic oxidative stress in the rats with type 1 diabetes. Diabetes mellitus was induced by single intravenous injection of streptozotocine (45 mg/kg) into the tail vein of the rats. Four groups of rats were divided as follow: normal, normal treatment, diabetic, and diabetic treatment groups. Normal treatment and diabetic treatment groups received intra-orally fullerene (1 mg/ kg/daily) up to day 60 following streptozotocine injection. Oxidative stress markers in the pancreas were evaluated on day 60 after inducing diabetes mellitus. Injection of streptozotocine significantly increased serum glucose level as well as food and water intake on all experimental days; it decreased body weight on day 60. Streptozotocine increased MDA level and decreased GSH level and SOD activity in the pancreas. Fullerene significantly decreased food and water intake and increased body weight as compared with the diabetic group. Fullerene also could normalize the pancreatic MDA and GSH markers. The present study suggested that fullerene can decrease diabetic symptoms via its anti-oxidant activity in the pancreas in the rats with type 1 diabetes mellitus.Resumo em Inglês:
Abstract A collaborative physician-pharmacist relationship is a fundamental component of a patient’s primary care. The aim of this study was to investigate the attitude of physicians toward collaborative work with community pharmacists in Sulaimani City, Iraq. A cross sectional design was utilized, and a questionnaire was sent to 60 physicians, of whom 47 completed the questionnaire. A total of 26 (55.3%) physicians stated that they had a history of collaboration with pharmacists in their routine daily work. During/before the treatment process, more than one-third of the physicians “rarely” practiced collaboratively, and one-fifth “never” collaborated. There was little agreement on the community pharmacist’s recommendations; however, after the treatment decision by the physician, a higher degree of agreement was reported, and the number of physicians who were “rarely” or “never” practiced collaboratively decreased to less than 5%. Furthermore, the physicians’ perspective on the pharmacists’ role showed that advising patients on drug administration (85.1%) and preventing drug interactions (76.6%) were the most common duties of the community pharmacists. Physicians agreed on several barriers with respect to collaboration with pharmacists. In conclusion, the physicians’ perspective on the engagement of the community pharmacist in the management of patients was relatively limited. The pharmacist’s recommendation was more accepted after medications were prescribed than before or during decision making on the treatment.Resumo em Inglês:
Abstract Snake envenomation is a public health problem, and while serum therapy prevents death, the local effects of venoms can lead to amputations or morbidities. Thus, alternative treatments deserve attention. In this study, we tested eight derivatives of 1,2,3-triazole against some toxic activities of Bothrops jararaca venom. The derivatives were synthesized, and their structures analyzed by infrared and nuclear magnetic resonance. After that, the ability of compounds to inhibit hemolysis, coagulation, proteolysis, hemorrhaging, edema, and lethal activities of B. jararaca venom was investigated. The derivatives were incubated with B. jararaca venom (incubation protocol), administered before (prevention protocol) or after (treatment protocol) injecting venom into the mice. Then, hemorrhaging assay occurred. As a result, most of the derivatives inhibited the activities, even if they were incubated, injected before or after B. jararaca venom. However, the derivatives TRI 07 and TRI 18 seemed to be the most efficient in impairing hemorrhaging. The derivatives showed a low drug score of toxicity based on an in silico technique. Therefore, the derivatives fulfilled physicochemical and biological requirements to become drugs, and they may be a brand new initiative for designing antivenom molecules to complement antivenom therapy to efficiently block tissue necrosis or any other local effects.Resumo em Inglês:
Abstract The current research focused on screening and finding the significant independent variables in stavudine loaded tablet, followed by optimizing the best formulation using central composite design. The objective of the study to develop stavudine loaded controlled release tablet utilizing reduced factorial design, followed by optimization technique as well as characterization of prepared tablets. Preliminary trial batches were prepared using different grades of hydroxypropyl methylcellulose. The resolution-IV reduced factorial design was selected to screen the significant independent variables in the dosage form design. A total number of eight runs were prepared and responses were recorded. The signified factors identified by half-normal and Pareto chart. The prepared tablets are evaluated for various physiochemical characterizations. Three dependent responses such as hardness, dissolution at 6 hour and 12 hours are considered in optimization process. Later on, drug-polymer interaction study was carried out. The principal of the study design based on finding the best formulation with prefixed set parameter values utilizing the concept of screening technique. It observed that HPMC K15M (57.18 %), HPMC K100 (66.32 %) and PVP K30 (7.97 %) as best composition in a formulation batch would fulfill the predetermined parameter with specific values.Resumo em Inglês:
Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as single-agents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl-2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.Resumo em Inglês:
Abstract Clinical pharmacists have been increasing their participation mainly through actions aimed at patient care, with international studies demonstrating favorable cost-benefit ratio from pharmacists interventions. However, there are few studies carried out in Brazil about the subject. This study aims to assess the economic impact of pharmaceutical interventions (PIs) in a hospital setting performed in October 2018. Each performed PI was registered and associated with the direct cost of drugs for economic impact analysis. A total of 185 PIs were evaluated, comprising 106 patients. The most intervened drugs were antibiotics, presenting the greatest economic impact, R$2,370. The total economic impact was R$2,578, mainly in the Pediatric Intensive Care Unit that represented R$1,701. Regarding the economic impact by PI as the “Suspension of drug without indication” saved R$1,360 while the “Inclusion of required drugs” cost R$807. It was estimated that the savings would be R$30,936 and, if PIs were performed at day zero, the savings would be R$79,728 per year. An average of 1.75 PI per patient was performed with an economic impact of R$14 per PI. Our results showed that clinical pharmacist’s role in the evaluation of pharmacotherapy is important for patients’ health and represents a positive economic impact.Resumo em Inglês:
Abstract The genus Stachys includes about 300 cosmopolitan species, making it one of the largest genera of the Lamiaceae family. The purpose of this paper is to present a review of Stachys species in the flora of Serbia among which some species are endemic to the Balkan Peninsula. This review comprises morphological, phytochemical, medicinal and food application of 17 taxa: S. аlopecuros, S. аlpina, S. аnisochila, S. аnnua, S. аtherocalyx, S. cretica subsp. cassia, S. germanica, S. leucoglossa, S. milanii, S. officinalis, S. palustris, S. plumose, S. recta, S. tymphaea, S. scardica, S. serbica, and S. sylvatica. The species of the genus Stachys are rich sources of biologically active substances and well known for their worldwide application. For most of the Stachys species, it has been shown that their extracts possess biological activities such as antibacterial, anti-inflammatory, antioxidant, and anticancer. The main goals of this review include the morphological description of species, representation of the major secondary metabolites, and presentation of traditional knowledge in food preparation.Resumo em Inglês:
Abstract The chemical hydroxymethylation of the antimicrobial nitrofurazone leads to the prodrug NFOH, also increases the anti-T. cruzi activities (in vitro and in vivo), as well as showed non-genotoxic (Ames and micronucleus assays). In the present study, we assessed the anti-T. cruzi effect of the NFOH In vivo - in acute Swiss and C57Bl/6 experimental Chagas models. The treatment started at 5 days post-infection during 20 consecutive days (orally, once day, 150mg/kg), and the parasitaemia as well as histopathology analysis were performed. In both experimental murine models, NFOH was able to reduce parasitemia blood avoiding parasitic reactivation, during immunosuppression period (dexamethasone 5mg/kg, 14 days), in 100% of the mice, and decrease tissue parasite nests, demonstrating absence of amastigote forms in all organs (100%) analyzed, data similar to benznidazole (BZN). Therefore, the results shown here pointing to the NFOH as promising compound for further preclinical studies, being a high potential drug to effective and safe chemotherapy to Chagas disease.Resumo em Inglês:
Abstract Pharmacist-physician collaboration is a strategy for optimizing patient care and improving health outcomes. Nevertheless, there is a lack of information in Brazil about collaborative practices among these professionals. The aim of this study was to measure collaborative attitude of pharmacists and physicians who were working together in a teaching hospital. A cross-sectional study was conducted from June 2018 to January 2019 with pharmacists and physicians working in a teaching hospital in Northeastern Brazil. These professionals were invited to provide responses to the Brazilian version of the “Scale of Attitudes Towards Pharmacist-Physician Collaboration” (SATP2C); their scores ranged between 16 and 64 points. The software Epi Info TM (version 3.5.4) was used for data analysis, and data were expressed in means. Forty-four professionals participated in this study. The mean age was 33.5 (DP = 7.1) years. More than half of participants were male (n = 25, 56.8%). The means from the SATP2C for pharmacists and physicians were 54.20 and 50.91, respectively, indicating good collaborative attitudes. There was no statistical difference between the mean scores of pharmacists and physicians. Participants showed a predisposition for collaborative teamwork. Future studies should focus on understanding the process by which collaboration translates into clinical practice.Resumo em Inglês:
Abstract The inhibition of calculi forming oxalate by dietary Basella rubra plant organs leaf and stem pod has been investigated. The weight reduction assay was studied. Also a concoction of the plant organs was tested. Leaf extract was found with considerable activity whereas the concoction seems to be not much active as the stem pod extract. Soluble oxalate of the plant organs are partially removed prior to extraction of active constituents. The active component/s seem to be a non-protein and non-tannin molecule/s that may act through inhibition of calcium accumulation there by proving the positive activity against the calculi or kidney stone. Regular consumption of leaf and stem pod extracts of our plant would be helpful in calculi prophylaxis.Resumo em Inglês:
Abstract The aim of this study is the association between the scores of disease activity, functional capacity and quality of life among patients diagnosed with rheumatoid arthritis, under clinical treatment at the Regional University Hospital of Campos Gerais - Wallace Thadeu de Mello and Silva. The sample was composed by volunteer patients, who freely underwent 3 research questionnaires. With the results of the survey, the disease activity score was correlated to the functional capacity and the quality-of-life scores. A mean of 3.87 and 1.2 was observed for the disease activity and the functional capacity scores, respectively, yet not achieving a correlation between those two variables. A strong correlation between the disease activity and the “functional capacity”, “general health status” and “mental health” domains was found. The lowest average observed corresponded to “physical limitation”, from the quality-of-life questionnaire. There was no statistically significant correlation between disease activity and functional capacity, although disease activity seems to affect the mental health, general health status and functional capacity of patients.Resumo em Inglês:
Abstract Nowadays, the number of medicines manufactured using advanced technologies such as biotechnology, nanotechnology, and 3D printing is increasing along with the accelerated pace of technological change. Evaluating high technology medicines from the perspective of community pharmacists is important for the quality of the pharmacy practice. The aim is to analyze the knowledge, attitude, and behavior of community pharmacists regarding advanced technology medicines and to examine the social and ethical aspects from the pharmacist’s perspective. A face-to-face cross-sectional survey was conducted with each of the 879 community pharmacists in Istanbul using a stratified sampling method. In this context, the gaps in pharmacists’ knowledge of high technology medicines were determined. It has been found that the pharmacists’ level of knowledge and willingness to learn new technologies differs according to the current education levels of the pharmacists and diversity in patient profiles. The pharmacists should close the knowledge gaps and update their information about medicines that are manufactured via the implementation of advanced technologies. The more pharmacists adapt to technology, the better guidance they can offer to society. This will also ensure that communication between the pharmacist and the patient to be built on trust, and significantly improve pharmacy practice.Resumo em Inglês:
Abstract The delivery of clinical pharmacy services has been growing in Brazilian community pharmacies, and it is necessary to have a comprehensive understanding of the topic. This scoping review aimed to provide an overview of Brazilian studies about clinical pharmacy services in community pharmacies. Original research articles, with no restriction of time, study design, or patient’s health condition, were included. Searches were conducted in PubMed, Scopus, Web of Science, Scielo, and Lilacs. Two reviewers conducted the screening, full-text reading, and data extraction independently. ROB and ROBINS-I were used for the assessment of quality. Charts and tables were built to summarise the data. Seventy-two articles were included. A diversity of study designs, number of participants, terms used, and outcomes was found. São Paulo and Sergipe States had the highest number of studies (n=10). Pharmacists’ interventions were not fully reported in 65% of studies, and most studies presented an unclear risk of bias. Studies were very diverse, impairing the comparisons between the results and hindering their reproducibility. This review suggests using guidelines and checklists for better structuration of pharmacists’ interventions as well as reporting results and measuring fidelity in future research.Resumo em Inglês:
Abstract Resistant starch is particularly concerned with beneficial effects in regulating blood glucose concentration and lipid metabolism, reducing the risk of diabetes and cardiovascular diseases. This study aimed to validate the effects of wheat starch acetate containing 32.1% resistant starch on postprandial blood glucose response and lipid profile on obesity, dyslipidemia Swiss mice induced by a high-fat diet. The result showed that there was a restriction on postprandial hyperglycemia and remained stable for 2 hours after meal efficiently comparing with the control group fed natural wheat starch. Simultaneously, when maintaining the dose of 5g/kg once or twice a day for 8 weeks, wheat starch acetate to be able to reduce body weight and blood glucose, triglyceride, cholesterol levels compared to the control group (p<0.05).Resumo em Inglês:
Abstract In the last decades, ferroptosis and its relationship with Parkinson’s disease have gained significant attention. Compounds that affect ferroptosis and iron-dependent pathways in particular, have possible candidates for study in this context.Sinapic acid is an iron-chelator and high antioxidant bioactive phenolic acid. Its neuroprotective action, due to the antioxidant capacity, has been shown in several experimental models.However, the relationship between iron and antioxidant actions is still misunderstood and therefore, in the current study, we tried to investigate the effects of sinapic acid in rotenone-induced Parkinson’s disease with the aspect of ferroptosis and iron-dependent alterations.The Parkinson’s disease model was induced by a single dose intrastriatal and intrategmental rotenone (5µg/µl) injection.Sinapic acid (30mg/ kg) was orally administered during a 28-day period after the Parkinson’s disease model was validated.Our results demonstrated that sinapic acid treatment attenuated rotenone-induced increase of serum transferrin and iron levels.Furthermore, sinapic acid inhibited rotenone-induced heme oxygenase-1(HO-1) increase and decrease of glutathione peroxidase-4 (GPx-4) levels in brain tissue. Also, sinapic acid treatment decreased motor impairment, likely as a result of the ameliorative effects on the tyrosine hydroxylase immunoreactivity loss after the rotenone insult.Our study suggests that the iron regulatory role of sinapic acid possibly plays a role in the protective effect on rotenone-induced neuronal damage.Resumo em Inglês:
Abstract Nephrotoxicity and hepatotoxicity are frequently seen adverse effects during cisplatin chemotherapy. In this study, we investigated the effects of agomelatine on cisplatin-induced toxicity in the kidney and liver. Animals were administered with a single dose of cisplatin (7 mg/kg, i.p.) and treated with agomelatine (20 and 40 mg/kg, p.o) for seven days. Renal and hepatic functions were evaluated by measuring concentrations of creatinine, BUN, AST and ALT in the serum. Oxidative stress and protein peroxidation were assessed by measuring SOD, CAT, GSH and AOPP levels in both tissues. Serum PON-1 levels were also evaluated. Histopathological analysis was performed to determined structural changes in the kidney and liver. Agomelatine (20 mg/kg) treatment approximately halved cisplatin-related increase in serum creatinine, BUN, AST and ALT levels. Agomelatine (20 mg/kg) significantly prevented the cisplatin-induced excessive decrease in SOD, CAT, GSH in both tissues and serum PON-1 levels. Agomelatine (20 and 40 mg/kg) protected the structural integrity of the kidney against cisplatin-insult. Although agomelatine (40 mg/kg) protected the kidney and showed parallel results with 20 mg/kg biochemically, it failed to show the same liver tissue effects in both analyses. Although agomelatine protected against cisplatin-induced toxicity in the kidney and liver, care should be taken with higher doses for possible hepatotoxicity.Resumo em Inglês:
Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of β1-adrenergic receptor (β1AR), β-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac β1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox.Resumo em Inglês:
Abstract The current investigation was used to improve the rate of dissolution of an anti-diarrheal drug i.e., racecadotril (RT) at low pH conditions (i.e., in the stomach) by reducing the water secretion and electrolyte in to the intestine by liquisolid tablets. Different formulations (liquisolid) were prepared using Avicel PH 102 as a carrier. Aerosil 200 as a coating material and sodium starch glycolate used as a disintegrant. Polyethylene glycol 200 was used as a non-volatile vehicle to dissolve the drug. FTIR, DSC, XRD and dissolution studies were conducted to characterise liquisolid tablets. Characterisation studies indicated that no interactions between carrier and drug. Solid state characterization had shown a reduction in crystallinity that further supports increment in solubility and dissolution. The optimised formulation showed a significant increase in dissolution i.e., 99.54±0.62% in 30 min compared to directly compressible tablets (38.47±0.26%). The % dissolution efficiency of racecadotril liquisolid tablets 76.86% compared to marketed tablet (27.56%) and conventional direct compression tablet (17.11%). Significant reduction in mean dissolution time of racecadotril from liquisolid tablets (6.84 min) compared to direct compression tablet (44.57 min), indicating faster release of drug and faster onset of action. Formulation of liquisolid tablets could enhance solubility, dissolution and bioavailability of racecadotril.Resumo em Inglês:
Abstract This study investigatedthe efficacy and safety offluticasone propionate nasal spray in treatment of adenoidal hypertrophic snoring in children.Fifty-six children with adenoidal hypertrophic snoring were enrolled. According to adenoidal-nasopharyngeal ratio (ANR) in lateral nasal X-ray examination,the children were assigned in moderategroup (23 cases) and severegroup (33 cases).The fluticasone propionate nasal spray was used for all patientsfor 4 weeks.In 56 patients, after treatment, compared with before treatment, the snoring, sleep apneaand nasal obstruction scores in moderategroupand the nasal obstruction score in severegroupwere significantly decreased,respectively (P < 0.05).The decreases of snoring, sleep apnea, mouth breathing and nasal obstruction scores after treatment in moderate group were significantly higher than those in severe group, respectively (P <0.001).After treatment, in 18 patients with ateral nasal X-ray examination,the adenoid size was obviously reduced, and the nasopharynx airway was obviously enlarged. The meanANRdropped from 0.76±0.10 to 0.72±0.09(P <0.001).Duringtreatment, only 2 of 56 patients were reported with intranasal dryness and occasional epistaxis, which were self-healed without treatment.Fluticasone propionate nasal spray is effective and safe for treatment of children’s snoring caused by adenoidal hypertrophy.Resumo em Inglês:
Abstract The purpose of this study is to evaluate the preventive effects of Urtica dioica (UD) on muscle ischemia/reperfusion (I/R) injury. A total of 27 male Wistar rats were divided into three groups as the control group (1), I/R + saline group (2), and I/R+UD group (3). Group 1 did not receive any treatment. Group 2 was administered a total of 2mL/kg saline (1mL/kg before ischemia and 1 mL/kg after reperfusion), and group 3 was given a total of 2mL of UD (1mL/kg before ischemia and 1mL/kg after reperfusion) as treatment. Saline and UD were administered via intraesophageal canula once a day for five days. At the end of five days, all the rats were exposed to muscle ischemia for 60 min followed by 60 min of reperfusion of the bilateral hindlimbs induced using a tourniquet. Muscle tissue histopathologies were evaluated by light microscopy. Furthermore, oxidative/nitrosative stress biomarkers such as catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrotyrosine (3-NT), nitric oxide (NO), and myeloperoxidase (MPO) as an inflammatory marker in tissue samples were measured. UD treatment significantly decreased oxidative/nitrosative stress biomarker levels and MPO (p<0.05). We established that UD treatment could alleviate muscle injury induced by muscle I/R in rats by inhibiting the inflammation and oxidative/nitrosative stress.Resumo em Inglês:
Abstract Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.Resumo em Inglês:
Abstract The present research evaluated the anti urolithic potential of Cyperus rotundus tubers extract using in silico, in vitro and in vivo techniques. In silicostudy was performed of Cyperus rotundus constituents and pathological protein oxalate oxidase (PDB Id: 2ETE). In vitrostudy, nucleation and aggregation assay involved for assessment of ethanol extract of Cyperus rotundus tuber (50-3000 µg/ml).In vivo studies involved that the Cyperus rotundusethanolic extract (100, 200 and 400 mg/kg B.wt.) wastreatedonsodium oxalate induced urolithiatic rats for seven days,evaluated kidney function by urine and serum biochemical analysis and statistical analysis performed usingGraphPad prism5 software.In silico results showedthat Cyperus rotundus constituents,Humulene epoxide, 4-Oxo-alpha-ylangene, Cubebol were exhibited better binding energyonoxalate oxidase.Ethanolic extract of Cyperus rotundustuber was exhibited nucleation, aggregation of calcium oxalate monohydrate crystals inhibition in dosedependent manner. Sodium oxalate treatment was triggered biochemical changesin the urine that have been substantially prevented by the ethanolic extract of Cyperus rotundus tuber. The current findings Cyperus rotundus anti urolithic activity due to antioxidant essential oils. The molecular docking results could be used to optimize lead and develop the appropriate urolithiasis treatment.Resumo em Inglês:
Abstract A phytochemical study of Tecoma genus (Bignoniaceae) was accomplished by antitumor activity of ethanolic extracts. Species of this genus are composed of small shrubs often used as ornamental plants. The Tecoma stans species is used in folk medicine for different purposes. Recent work shows in vitro anticancer activity against human breast cancer. The ethanolic extracts from leaves and trunks of Tecoma casneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were tested in vitro. The assays used were against line tumor cells by the MTT method and the most active extracts were further studied. In this way, the ethanolic extract from T. stans var. stans trunks presented the higher cytotoxicity against the tumor cell lines studied (CC50 0.02 to 0.55 µg/ml) when compared to the other extracts tested (CC50 0.08 to 200.0 µg/ml). Accordingly, this extract was selected for chromatographic fractionation from which five known lignans were isolated. Further, paulownin, paulownin acetate, sesamin, olivil and cycloolivil were identified using 13C and 1H NMR, IR, UV and spectroscopy and spectrometric MS techniques. These isolated compounds were tested and exhibited CC50 ranging from 13.01 to100.0 µg/ml which is superior to the ethanolic extract of trunk of T. stans.Resumo em Inglês:
Abstract Epidemiological studies suggest that acute kidney injury has certain effect on myocardial function. In this study, for the first time, we tested a boron compound namely lithium tetraborate an act as an anti-oxidant and anti-inflammatory agent in ischemia-reperfusion injury. For this, we employed an in vivo rat model with kidney ischemia reperfusion injury to evaluate cardiac injury to clarify the mechanisms of lithium tetraborate. The evaluation of cardiac injury through kidney artery occlusion and reperfusion rat model indicated that lithium tetraborate could (1) reduce oxidative stress-induced endothelial dysfunction; (2) attenuate the inflammatory response of cardiac cells; and (3) alleviate the apoptosis and necrosis of myocytes. In summary, lithium tetraborate demonstrates significant therapeutic properties that contribute to the amelioration of cardiac damage, and it could be a promising candidate for future applications in myocardial dysfunction.Resumo em Inglês:
Abstract The present study was designed to evaluate the beneficial synergistic effects of S-allyl Cysteine (SAC) and Taurine (TAU) on hyperglycemia, lipid profile and renal damage markers in type 2 diabetes mellitus (T2DM) in rats. Experimental T2DM was developed by administering an intraperitoneal single dose of nicotinamide (NA; 230 mg/kg) and streptozotocin (STZ; 65 mg/ kg) in adult rats. Control and diabetic rats were treated with SAC (150 mg/kg); TAU (200 mg/ kg) or SAC and TAU (75+100 mg/kg) combination for four weeks. Measurements of traditional markers of kidney toxicity in serum, such as blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), together with serum cholesterol/triglyceride such as serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) may yield a snapshot of renal damage and lipid profile in NA/STZ-treated rats. The variation in levels of fasting blood glucose, glycosylated hemoglobin, insulin and lipid profile was significantly augmented in SAC/TAU treatment group. The diabetic group showed elevated renal injury markers in serum, which were decreased significantly by SAC/TAU treatment. Thus the results of the experiment clearly indicate the potential of the SAC/TAU combination in improving diabetic complications.Resumo em Inglês:
Abstract The main purpose of this work was to compare the effects of the four preparation methods on the TFLX/HP-β-CD inclusion complex. The effects of different preparation methods on the inclusion complex were investigated by SEM, DSC, PXRD, FT-IR and 1H NMR. All the characterization information indicated that the four preparation methods could cause interaction between TFLX and HP-β-CD, but the inclusion complex prepared by solvent evaporation has more reaction sites. Phase solubility experiments demonstrated that the inclusion reaction was spontaneous. In vitro dissolution experiments showed that the dissolution of the inclusion complex in water was: solvent evaporation method (64.39%) > grinding method (42.37%) > ultrasonic method (40.00%) > freezing method (36.08%), and all higher than pure TFLX and physical mixture. These results suggest that the solvent evaporation is the most suitable method for preparing TFLX/HP-β-CD inclusion complexes.Resumo em Inglês:
Abstract In this study, we investigated the effects of polymers on the pharmaceutical cocrystal formation process. Ibuprofen (IBU) was selected as the active pharmaceutical ingredient (API), nicotinamide (NIC) and saccharin (SAC) as the cocrystal coformer (CCF), ethanol/water as the solvent, polyvinylpyrrolidone (PVP) and poly (ethylene glycol) (PEG) as the representative polymers. We prepared IBU-NIC and IBU-SAC cocrystals in ethanol-water cosolvent in the absence or presence of polymers. Cocrystal screening products were characterized by FTIR, DSC, PXRD, and HPLC. The results showed that the mixture of IBU and IBU-NIC cocrystal can be prepared in ethanol-water cosolvent without polymers. The addition of PVP facilitates the formation of pure IBU-NIC cocrystal; however, no cocrystal was formed in PEG solutions. SAC could not cocrystallize with IBU in the ethanol-water solvent in the absence of polymers. Neither PVP nor PEG could facilitate the formation of the IBU-SAC cocrystal.Resumo em Inglês:
Abstract To investigate the pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus herb-pair in kidney-yin deficiency model, which was made by continuously oral gavage of thyroxine. A simple and rapid LC-MS/MS method was developed and validated for the determination of loganin and morroniside in rat plasma and used for the pharmacokinetics study. The kidney-yin deficiency significantly changed the AUC(0-∞), Cmax and CLz/F of loganin and morroniside. The T1/2z of morroniside increased significantly in the kidney-yin deficiency rats. For the pharmacodynamics study, the liver index, kidney index, and ALT, TBIL, UREA, CREA level in the kidney-yin deficiency mice were examined. The herb-pair had been proved to be effective for the treatment of kidney-yin deficiency by affecting the liver, kidney, ALT, UREA and CREA, which showed positively correlated with the dose. The pharmacokinetics and pharmacodynamics studies in the pathological status could offer more valuable information for the future application of Astragali Radix-Corni Fructus herb-pair.Resumo em Inglês:
Abstract Neuropathic pain (NP) affects more than 8% of the global population. The proposed action of the transient receptor potential ankyrin 1 (TRPA1) as a mechanosensor and the characterization of the transient receptor potential melastatin 8 (TRPM8) as a cold thermosensor raises the question of whether these receptors are implicated in NP. Our study aimed to evaluate the involvement of TRPA1 and TRPM8 in cold and mechanical signal transduction to obtain a comparative view in rat models of streptozotocin-induced diabetes (STZ) and chronic constriction injury of the sciatic nerve (CCI). The electronic von Frey test showed that STZ rats presented mechanical allodynia that was first evidenced on the 14th day after diabetes confirmation, and four days after CCI. This phenomenon was reduced by the intraplantar (ipl) administration of a TRPA1 receptor antagonist (HC-030031; 40 μL/300 μg/paw) in both NP models. Only CCI rats displayed cold hyperalgesia based on the cold plate test. The pharmacological blocking of TRPA1 through the injection of the antagonist attenuated cold hyperalgesia in this NP model. STZ animals showed a reduction in the number of flinches induced by the intraplantar injection of mustard oil (MO; TRPA1 agonist; 0.1%/50 μL/paw), or intraplantar injection of menthol (MT; TRPM8 agonist; 0.5% and 1%/50 μL/paw). The response induced by the ipl administration of MT (1%/50 µL/paw) was significantly different between the CCI and SHAM groups. Together, these data suggest a different pattern in nociceptive behavior associated with different models of NP, suggesting a variant involvement of TRPA1 and TRPM8 in both conditions.Resumo em Inglês:
Abstract Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.Resumo em Inglês:
Abstract Aloe vera possesses a great therapeutic importance in traditional medicine. It has attracted the attention of modern medical fields due to its wide pharmacological applications. The bioactive substances in Aloe vera proved to have antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Taken into our consideration the long history of clinical applications of Aloe vera in traditional medicine, especially for promoting the healing of cutaneous wounds with rare adverse effects, it provides a cheap alternative to many expensive synthetic drugs. Recent techniques in tissue engineering created novel scaffolds based on Aloe gel extracts for wound healing applications. Nonetheless, further guided researche is required to foster the development of Aloe vera based scaffolds for the benefit of worldwide populations. Here, I systemically summarize the main events following wounding and the mechanism of action of Aloe vera in promoting the healing process. I hope to provide a solid piece of information that might be helpful for designing new research studies into this topic.Resumo em Inglês:
Abstract Benign prostatic hyperplasia (BPH) is a multifactorial disease, highly associated with aging and characterized by increased prostate smooth muscle (PSM) contractility. Animal models have been employed to explore the aging-associated PSM hypercontractility; however, studies have focused in old animals, neglecting the initial alterations in early ages. The determination of prostatic dysfunctions onset is crucial to understand the BPH pathophysiology and to propose new BPH treatments. Considering that PSM contractility in 10-month-old rats has already been explored, the aim of the present study was to characterize the PSM contractility in younger rats. Male Wistar control (3.5-month-old), 6- and 8-month-old rats were used. Concentration-response curves to phenylephrine and electrical-field stimulation (EFS) were conducted in prostate from all groups. For the first time, we showed that 6- and 8-month-old rats exhibit PSM hypercontractility. The increased prostate contractility to phenylephrine starts around at 6-month-old, worsening during the aging. The 8-month-old rats exhibited hypercontractility to phenylephrine and EFS compared to the control and 6-month-old groups. Reduced phenylephrine potency was observed in 8-month-old rats, indicating an increased age-dependent prostate sensibility to this agonist. Collectively, our findings support the use of 6- and 8-month-old aged rats as new models to explore prostate hypercontractility in BPH.Resumo em Inglês:
Abstract Medicinal chemistry made it possible for pharmacists to propose pharmacodynamics and pharmacokinetics explanations of many existing drugs. Moreover, medicinal chemistry education provides pharmacy students with a reasonable understanding of drug physicochemical properties, mechanism of action (MOA), side effects, metabolism and structure-activity relationship (SAR). This paper highlights the importance of these medicinal chemistry key elements in understanding other pharmacy core courses, mainly pharmacology and clinical therapeutics. Such elements can be utilized as a tool for pharmacists while training or counseling their patients on the use of their treatments. Different new examples from the literature have been incorporated in this paper to show how chemical structures of existing drugs can provide essential information about main concepts in the education of pharmacology and clinical therapeutics, and the key structural elements for the discovery and development of other same class drugs.Resumo em Inglês:
Abstract Stroke is one of the most important health concerns worldwide. Calcium ions accumulation in the nerve cells and increase in the catecholamines level of the brain following cerebral ischemia/reperfusion (I/R) are accompanied by damaging effects. Therefore, the present study aimed to evaluate the effects of diltiazem, as a calcium channel blocker, and metoprolol, as a β-adrenoceptors antagonist, on I/R injury. In this study, 30 male Wistar rats were divided into control, I/R, metoprolol, diltiazem, and metoprolol plus diltiazem groups (n=6 in each). Metoprolol (1 mg/kg/day) and diltiazem (5 mg/kg/day) were injected intraperitoneally (i.p.) for 7 days before I/R induction. On day 8, the animals underwent ischemia by bilateral common carotid arteries occlusion for 20 min. Histopathological analysis showed a significant reduction in leukocyte infiltration in diltiazem, metoprolol, and diltiazem plus metoprolol treated rats compared with the I/R group (P<0.05, P<0.01, P<0.01, respectively). In addition, in all treated groups, myeloperoxidase activity and malondialdehyde levels in the brain tissue significantly declined compared with the I/R group (P<0.001). Furthermore, pre-treatment with diltiazem and metoprolol alone or in co-administration remarkably reduced infarct size following I/R (P<0.001). Overall, the results indicate the considerable neuroprotective effects of metoprolol and diltiazem in cerebral I/R.Resumo em Inglês:
Abstract Recent studies have demonstrated that 30% of the world’s population suffers of anemia, half of the cases are related to iron deficiency, and the most common treatment is the use of iron supplementation. In this framework, the iron and zinc determination from different dietary supplements was performed by flame atomic absorption spectrophotometry. Concerning the dissolution of supplements, direct acid dissolution, wet digestion, and microwave digestion (MW) techniques were used for sample preparation. The iron and zinc recovery results demonstrated that the MW technique was the most appropriate for all of the supplements with the highest metal recovery yields. Moreover, the method validation parameters referred to a linear range for iron of 0.1-4 mg L-1 with a regression coefficient (R2) of 0.9998 ± 0.002, while for zinc it was 0.01-1 mg L-1 (R2 = 0.9997 ± 0.003). The limit of detection and quantification values were calculated as 0.03 and 0.09 mg L-1 for iron and 0.01 and 0.02 mg L-1 for zinc, respectively. The accuracy of the method was evaluated from the % recovery yield for iron and zinc, which, respectively, resulted in an oscillate of 99.2% to 102%, and 99.4% to 100.4% for the dietary investigated supplements. The precision of the method was determined by intra-day and inter-day precision with a relative standard deviation that was <2.0%.Resumo em Inglês:
Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612).Resumo em Inglês:
Abstract The prevalence of epidemiological diseases, including diabetes, has continued to increase because of the adaption of Western culture and the lack of self-care activities among patients with diabetes. Therefore, in this cross-sectional study, we aimed to assess self-care plans and determinants among diabetes outpatients in Warangal. We conducted a prospective observational study among diabetes outpatient clinic in Warangal, India over 6 months from October 2019 to March 2020. We used the expanded Summary of Diabetes Self-Care Activities (SDSCA) questionnaire. A P value of less than < 0.05 was considered statistically significant. Respondents (mean age, 52.3 (standard deviation (SD), 11.01) years) had an overall SDSCA score of 49.18 ± 3.57 (SD). Mean scores for the diet, physical activity, foot care, medication adherence, and blood sugar testing scales were 12.79 (SD, 1.61), 10.24 (SD, 1.77), 15.67 (SD, 1.5), 5.66 (SD, 1.17), and 4.80 (SD, 0.68), respectively. Patients’ age, education, disease duration and hemoglobin A1C (HbA1C) levels of <7.5% (P < 0.001)) had significantly higher mean scores for blood sugar testing, diet, physical activity, and adherence (P < 0.001). The employment status is associated with all the domains of Summary of Diabetes Self-Care Activities (P < 0.001). Taken together, our results revealed that patients with diabetes in Warangal had poor self-care planning, highlighting the need for strengthening initiatives that generate awareness regarding diabetes and improving related self-care practices.Resumo em Inglês:
Abstract Brazilian pharmacists’ education and training aims to prepare them for the various activities they will undertake during professional practice, especially in the national health system (SUS). By using an exploratory transversal study based on a validated questionnaire, we have characterized the educational and training background of pharmacists working in SUS municipal units in Ribeirão Preto, State of São Paulo (SP), Brazil, and the frequency with which these professionals carry out several activities. Pharmacists working in these municipal outpatient units (N=44) graduated between 1981 and 2014 (56.8% of them graduated from public state or federal institutions), are predominantly female (84%), and are aged 25-57 years; 34% of these pharmacists have a “Generalist” degree, and 90.9% attended postgraduate programs, mostly specialization (75%). All the pharmacists pointed out the need for continuing education. The frequency with which they carry out activities varies, but those involving direct contact with patients predominate. Consultations, therapeutic follow-up, case discussions, and health promotion activities take place only occasionally. We concluded that pharmacists who work in the municipality of Ribeirão Preto, SP, are very much involved with dispensing, but not with health education or pharmacotherapeutic follow-up, so investing in education and training in these areas is necessary.Resumo em Inglês:
Abstract We aimed to measure the prevalence of adverse events related to oral hormonal contraceptive (OHC) use and their associated factors in undergraduate pharmacy students. A cross-sectional study was conducted by using an online questionnaire for female students of the Faculty of Pharmaceutical Sciences of the University of São Paulo from July to August 2020. A descriptive analysis of the data was carried out, which was followed by determining the prevalence ratios to identify possible factors associated with adverse events resulting from OHC. A total of 269 valid responses were obtained, among which 50.2% (n = 135) of the students reported using OHC as a contraceptive method and 21.2% (n = 57) affirmed that they had at least one adverse event related to OHC use, which corresponds to 42.2% of those who had used OHC. The most common adverse event was headache (70.2%), and a period of less than one month was the most cited (49.1%). Only migraine comorbidity was associated with the occurrence of adverse events related to OHC. These findings reinforce the high incidence of adverse events among OHC users and the low rate of discontinuation due to these events. There is a need to provide more information on contraceptive methods to users, including its risks and contraindications.Resumo em Inglês:
Abstract The aim of this work was to perform an extended stability study for the analgesic containing fentanyl, clonidine and ropivacaine in physiological saline solution 0.9% at different infusion sites, such as infusion bags, epidural infusion sets and syringes. The extended stability was assessed by an HPLC system equipped with a photodiode array detector set at 210 nm. The separation was conducted on a C18 column maintained at 40˚C and using an isocratic mobile phase consisted of buffer solution-methanol-acetonitrile (45:45:10, v/v/v). The presence of particulate matter and the pH of each solution were also investigated. Twenty-four hours after the preparation, the formation of one suspected product was observed and for all drugs, in 24 hours it was observed the concentration decrease in different sets (PVC infusion bags, syringes and epidural infusion administration sets). The pH values of each solution varied no more than 5% during the study and no particle was observed. Conclusion: The extended stability study was applied to the analgesic solution and promoted the detection of an unexpected peak in 24 hours. Based on it, further stability studies are necessary to determine the extended stability data.Resumo em Inglês:
Abstract A simple and selective liquid chromatography tandem with mass spectrometry (LC-MS/ MS) method for quantification of lobetyolin in rat plasma was developed and validated. Chromatographic separation was achieved on a Thermo ODS C18 reversed-phase column using 0.1% aqueous formic acid-methanol (50:50, v/v) in an isocratic elution mode at a flow rate of 0.4 mL.min-1. LC/MS performance was done in a positive ion ESI mode and the MS/MS transitions were monitored at m/z 419.3 [M+Na]+ → m/z 203.1 for lobetyolin and m/z 394.9 [M+Na]+ → m/z 231.9 for IS, respectively. The assay exhibited a linear dynamic range over 1.0-500 ng.mL-1 for lobetyolin in plasma. Both the precision (%RSD) and accuracy (RE%) were within acceptable criteria (<15%). Recoveries ranged from 87.0% to 95.6%, and the matrix effects were from 91.0% to 101.3%. After oral administration, the peak plasma concentration of lobetyolin was obtained as 60.1 ng.mL-1 at 1.0 h. The proposed LC-MS/MS method could be applied to a pharmacokinetic study employing 66 samples from 6 Wistar rats.Resumo em Inglês:
Abstract Protease-activated receptors (PARs) are metabotropic G-protein-coupled receptors that are activated via proteolytic cleavage of a specific sequence of amino acids in their N-terminal region. PAR2 has been implicated in mediating allergic airway inflammation. This study aims to study the effect of PAR2 antagonist ENMD1068in lung inflammation and airway remodeling in experimental asthma. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with ENMD1068 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs were removed at different time intervals after OVA challenge to analyze inflammation, airway remodeling and airway hyperresponsiveness. Ovalbumin promoted leukocyte infiltration into BALF in a PAR2-dependent manner. ENMD1068 impaired eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in the lung parenchyma into BALF and reduced the loss of dynamic pulmonary compliance, lung resistance in response to methacholine, mucus production, collagen deposition and chemokine (C-C motif) ligand 5 expression compared to those in OVA-challenged mice. We propose that proteases released after an allergen challenge may be crucial to the development of allergic asthma in mice, and PAR2 blockade may be useful as a new pharmacological approach for the treatment of airway allergic diseases.Resumo em Inglês:
Abstract Instrumental techniques are preferred over bioassay methods for antibiotic quantification mainly due to speed and ability to quantify metabolites in biological samples; however, the potency and biological activity of these drugs cannot be assessed. Two methods - agar well diffusion (bio-assay) and spectrophotometric methods were used to evaluate amikacin sulfate injection. Agar plates were inoculated with S. aureus inoculum; zones of inhibition from its susceptibility to amikacin were obtained, while spectrophotometric absorption at 650 nm of ninhydrin- derivatized amikacin in phosphate buffer (pH 8) was measured. Methods performance showed linearity from 1 - 16 μgmL-1 (bioassay, r = 0.9994) and 10-50 μgmL-1 (spectrophotometric, r = 0.9998). Molar absorptivity was 2.595 x 104 Lmol-1cm-1. Limits of detection and quantification were 1.07 and 3.24 μgmL-1 respectively for bioassay method, while corresponding values for spectrophotometric method were 0.98 and 2.97 μg mL-1. Relative standard deviations were ≤ 2.0% for both methods, with recoveries from 95.93 - 100.25%. Amikacin in brands ranged from 97.53 ± 2.68 to 100.84 ± 1.82%, student’s t-test was ≤ 2.78 (n = 4) with respect to label claim for both methods. Experimental paired t-test (t = 2.07; n = 4) and F-test (F = 3.94; n = 4) values indicated no significant difference between both methods, hence comparable and can jointly be used in quality control assessment of antibiotics.Resumo em Inglês:
Abstract The World Health Organization recognized the use of herbal medicines as a therapeutic resource and its application in the primary attention to heath. The begin of this expansion was in 2006, with the National Policy on Integrative and Complementary practices of the Unified Health System (SUS). This research aimed to evaluate the questionnaires applied to doctors, who may have prescribed industrialized herbal medicines and to identify the difficulties involved with the implementation of this therapy as an integrative and complementary practice. It is a quantitative, observational and transversal study conducted in the municipality of Pinhais/Brazil. The questionnaire applied had as themes the experience of personal use of industrialized herbal medicines, improvement after their use. Forty-four individuals from four different nationalities: Brazilian (88.64%), Cuban (6.82%), Mexican (2.27%) and Argentinian (2.27%), ages between 25 and 69 years, mainly male sex (54.55%) answered the questionnaire. According to the study, the doctors consider herbal medicines an alternative to the conventional treatment and these medical professionals have already prescribed some industrialized herbal medications. Despite the difficulties faced by medical doctors with the prescription of herbs, it is possible to define strategies to assist these professionals, such as the incentive the actions by the governments.Resumo em Inglês:
Abstract Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.Resumo em Inglês:
Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study.Resumo em Inglês:
Abstract ROS (Reactive Oxygen Species) production is a usual plant reaction to environmental stresses such as allelopathy. Plants possess antioxidant enzymes to scavenge cells and resist against the ROS. This study was conducted to evaluate changes in antioxidant enzymes (CAT, GPX, APX) in radish seedlings in response to allelopathic effect of safflower root and shoot residues grown under normal irrigation and drought stress. Safflower allelopathic effect led to an increase in antioxidant enzymes activities. GPX activity increased more than CAT and APX. Radish seedlings exposed to safflower residue grown under drought stress showed more antioxidant enzymes activities. Root residues enhanced the activities of antioxidant enzymes greater than shoot. Seedlings exposed to root residues grown under drought stress had the highest level of antioxidant enzymes activities.Resumo em Inglês:
Abstract L-Malic acid is the Active Pharmaceutical Ingredient of the latest generation of compound electrolyte injection (STEROFUNDIN ISO, Germany) and plays a very important role in the rescue of critically ill patients. The optical purity of L-malic acid is a Critical Quality Attributes. A new reversed-phase high performance liquid chromatography (RP-HPLC) method for pre-column derivatization of D-malic acid enantiomer impurity in L-malic acid bulk drug was established. The derivatization reaction was carried out using (R)-1-(1-naphthyl)ethylamine ((R)-NEA) as a chiral derivatization reagent. The Kromasil C18 column was used with a detection wavelength of 225 nm, a flow rate of 1.0 mL·min-1, and a column temperature of 30 °C. The mobile phase was acetonitrile-0.01 mol·L-1 potassium dihydrogen phosphate solution (containing 20 mmol·L-1 sodium heptanesulfonate, adjusted to pH 2.80 with phosphoric acid) (at a ratio of 45:55) and the resolution of D-malic acid and L-malic acid derivatization products reached 1.7. The proposed method possesses the advantages of simple operation, mild conditions, stable derivatization products and low cost. Also it gave better separation and was more accurate than previous methods.Resumo em Inglês:
Abstract Safety culture is a product of values, attitudes, skills, and behavioral patterns, and it determines the commitment of the management to a secure organization. The evaluation of safety culture in hospitals helps to identify and manage the relevant patient safety issues in hospital routines and working conditions proactively. Thus, this study is aimed to evaluate patient safety culture in all the departments of a university hospital of medium complexity. This study employed a cross-sectional and analytical design employed in the Portuguese version of the Hospital Survey on Patient Safety Culture. A sample of all hospital staff participated in this study, which was conducted from December 2016 to May 2017. The percentage of positive responses was calculated to identify the strong and weak areas in patient safety. Of the 413 questionnaires distributed, 368 valid responses were returned. The response rate was, therefore, 89%. The overall percentage of positive responses was 50.3%. The “Supervisor/manager expectations and actions promoting patient safety” dimension obtained the highest percentage of positive responses (67.1%). The “Nonpunitive response to error” dimension was considered the weakest for safety culture, with only 22.9% positive responses. Furthermore, most professionals (70.6%) did not report any events in the previous 12 months. Nevertheless, 69.5% of participants considered patient safety within their unit/work area as “very good” or “great.” The results showed that the employees’ perception of patient safety diverged from the reality within the institution. Therefore, efforts should be made to promote an acceptable safety culture in all hospital areas.Resumo em Inglês:
Abstract The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr’s index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs’ gastrointestinal toxicity upon oral administration of ramipril.Resumo em Inglês:
Abstract In this study, we investigated the influence of the olfactive stimulus on visual attention. Two groups of 30 subjects participated in two experiments. Both experiments presented two arrays of fruits stimulus intercalated by an olfactive intervention. The stimulus was received in the form of images by the first group and in the form of words by the second group. An eye-tracking device monitored the timekeeping of visual attention dispensed in each stimulus. The results showed that olfactive priming influenced visual attention in both cases but with a greater degree in the images stimulus group. This study shows for the first time that image information is more susceptible to priming olfactive information than wording information. This effect may be associated with the formation of mental images in working memory, aroused by fragrances.Resumo em Inglês:
Abstract To evaluate possible new drugs for the treatment of Colorectal Carcinoma (CRC) using in silico tools was the main objective of this study. The method of analysis used was the in silico evaluation of tumor markers and their interaction with selected drugs, through the study of its pharmacokinetic and pharmacodynamic characteristics. A potential therapeutic target pointed out in this study was the Cell Division Cycle 25 B (CDC25B), belonging to the CDC25 phosphatase family. Overexpression of CDC25 phosphatases is often associated with a wide variety of cancers. In addition, CDC25B is an oncogenic protein that induces neoplastic transformation. In CRC, CDC25B is overexpressed to activate the CDC2/cyclin B complex and improve the growth and survival of these tumors. Four drugs were identified for evaluation, with α-amyrin being selected for docking, because it was that had the best characteristics according to the methodology used. The α-amyrin ligand obtained the interaction energy value of -7.6 G (Kcal/mol), while the standard CDC25B ligand obtained -10.0 G (Kcal/mol). TThe results showed that the CDC25B protein was the only structure cocrystallized with α-amyrin and presented favorable outcomes in docking, being a candidate for further studies for its use in the CRC targeted therapy.Resumo em Inglês:
Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.Resumo em Inglês:
Abstract We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats.Resumo em Inglês:
Abstract Phytochemicals present in detox juices and probiotics have demonstrated protective effects on cardiovascular risk factors. The consumption of these products alone modulate metabolic mechanisms and biomarkers. However, the effects of the combination of detox juice and probiotics have not yet been evaluated on atherogenic parameters. A randomized controlled study was carried out with 40 healthy volunteers (20 men and 20 women), aged between 18 and 50 years old. The volunteers ingested 200mL of juice for 30 days. Before and after supplementation, the anthropometric and lipid profiles and plasma concentrations of TBARS, Myeloperoxidase, Glutathione, Protein and non-protein Thiols and Vitamin C were analyzed. A reduction in LDL-c (p=0.05), triglycerides (p=0.05) and a significant increase in HDL-c (p=0.002) was observed. There was a significant decrease in the concentrations of TBARS (p=0.01), myeloperoxidases (p=0.02) and a significant increase in the Vitamin C and GSH (p=0.01). There wasn`t improvement in anthropometric parameters and total cholesterol. The findings highlight that supplementation with probiotic detox juice improves the lipid and antioxidant profile, suggesting a possible positive effect in reducing the risk of cardiovascular disease in healthy volunteers. Nevertheless, more robust researches with a prolonged treatment period should be conducted.Resumo em Inglês:
Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.Resumo em Inglês:
Abstract 1’-acetoxychavicol acetate (ACA)-loaded nanostructured lipid carriers (NLCs) were formulated for prostate cancer therapy and to determine the optimal therapeutic dose, we developed a rapid, specific, and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method to quantify the ACA content in NLCs. The method was validated according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. Chromatographic separation of ACA from the lipid components was performed with an Agilent 1220 Infinity LC system and ultraviolet detector using an Agilent Poroshell C18 column (4.6 x 250.0 mm). The mobile phase consisted of acetonitrile and water (80:20 [v/v]) with a flow rate of 0.8 mL/min in isocratic mode. Linearity of the standard curve was assessed at an ACA concentration range of 5-200 µg/mL, and a 1/x weighted linear regression was adopted for the calibration curve. The calculated limits of detection and quantification were 0.59 µg/mL and 1.79 µg/mL, respectively. The mean percent recovery of ACA was 100.02% (relative SD, 2%), and the coefficients of variation for intraday and interday assays were within the values required by the ICH. We also demonstrated robustness of the method by altering the mobile phase ratio and flow rate. Furthermore, we proved specificity of the method for ACA by comparing chromatograms of the blank NLC and ACA-NLC. Hence, we effectively used this validated method to determine the drug-loading capacity and entrapment efficiency of the NLCs.Resumo em Inglês:
Abstract Herein the chemical constituents and the anti-pain properties of the essential oil from the stem bark of Casuarina equisetifolia L. (Casuarinaceae) grown in Nigeria were evaluated. The essential oil was obtained by hydrodistillation method in an all glass Clevenger-type apparatus, and characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The hot plate method was used to determine the anti-nociceptive property whereas the anti-inflammatory activity was evaluated by carrageenan-induced and formalin experimental models. The pale-yellow essential oil was obtained in yield of 0.21% (v/w), calculated on a dry weight basis. The main constituents of the essential oil were methyl salicylate (30.4%), a-zingiberene (15.5%), (E)-anethole (9.5%), b-bisabolene (8.6%), b- sesquiphellandrene (6.9%), and ar-curcumene (6.2%). In the anti-nociceptive study, the rate of inhibition increases as the doses of essential oil increases with optimum activity at the 30th and 60th min for all tested doses. The essential oil displayed anti-nociceptive activity independently of reaction time at the highest tested dose (200 mg/kg). The essential oil of C. equisetifolia moderately reduced pain responses in early and late phases of the formalin test. The oil inhibited the paw licking in the neurogenic phase (60-63%) compared to the late phase of the formalin test. The carrageenan- induced oedema model revealed the suppression of inflammatory mediators within the 1st - 3rd h. Thus, C. equisetifolia essential oil displayed both anti-nociceptive and anti-inflammatory activities independent of the dose tested. The anti-inflammatory and anti-nociceptive activities of C. equisetifolia essential oil are herein reported for the first time.Resumo em Inglês:
Abstract Kombucha (tea and biocelluose) has been used worldwide due to its high nutritional, functional, and economic potential. This fermented tea has been used in folk medicine to treat several pathological conditions and its biocellulose in the industrial sector. In this context, this paper presents a scientific literature review on the main phytochemicals of Kombucha and respective biological activities to assess their potential uses. The tea has presented a wide range of bioactive compounds such as amino acids, anions, flavonoids, minerals, polyphenols, vitamins, and microorganisms. Moreover, its biocellulose is rich in fibers. These compounds contribute to various biological responses such as antioxidant, hepatoprotective, antitumoral, antidiabetic, and antihypercholesterolemic effects. In this sense, both the tea and its biocellulose are promising for human use. Besides, Kombucha presents itself as a drink option for vegetarians and/or those seeking healthier diets, as its biocellulose can bring metabolic benefits. Our review demonstrates that both can be used as functional foods and/or sources of bioactive compounds for food and industrial applications.Resumo em Inglês:
Abstract The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 μg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 μg/mL, for LOR and 29.60 and 89.69 μg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines.Resumo em Inglês:
Abstract Depression plays an important role in non-adherence to medical recommendations. Fluoxetine is a first line of depression treatment. This study aimed to evaluate adherence to drug therapy in fluoxetine users by different methods. A cross-section study was conducted with 53 depressed patients on fluoxetine for at least six months. Drug therapy adherence was assessed by validated questionnaires [Brief Medication Questionnaire (BMQ) and Morisky-Green test (MG)] and by the blood concentration of fluoxetine and its active metabolite norfluoxetine. Blood samples were taken before the daily first dose of fluoxetine. The plasmatic concentration of fluoxetine and norfluoxetine indicated that 58.5% volunteers were within the recommended therapeutic range and thus considered adherent to drug therapy. However, questionnaires indicated a non-adherent majority: 41.5% patients had a high degree of adherence in MG and only 13.2% were adherent to pharmacological treatment in BMQ. Most fluoxetine users showed a plasma concentration of fluoxetine and norfluoxetine within the therapeutic range, despite the low adherence to the drug therapy evaluated by the questionnaires. Thus, we suggest that plasma levels of fluoxetine and norfluoxetine could be used as the main method to check adherence to treatment.Resumo em Inglês:
Abstract Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 μM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors.Resumo em Inglês:
Abstract Warfarin has been associated with bleeding and venous thromboembolism. Objective: This study aimed to estimate the association between bleeding and concomitant self-medication, and the incidence of adverse drug reactions in patients using warfarin. Setting: the public health network of Ijuí, a municipality in southern Brazil. This was an open prospective cohort, conducted for a period of 18 months with users of warfarin, treated at the public health service. The association between bleeding and self-medication was evaluated by means of the Cox Model with left truncation, using the time variable. Main outcome measurement: bleeding reported in the follow-up. Cases of thromboembolism and death were also registered. All patients treated with warfarin in the public health system of the municipality (98) were identified. Sixty-eight were interviewed and followed up, of whom 63 completed follow-up and five died during the study. Bleeding rates of 37.7 /100 patients/year, thromboembolism of 4.8/100 patients / year and deaths of 4.8 /100 patients / year were observed. The results showed that patients, who take warfarin and self-medicated present a two-fold increased bleeding, compared with those who do not self-medicate. The bleeding risk associated with self-medication ranged from 2.001 to 2.685; those values maintained their significance even when adjusted for number of interactions, CYP polymorphism, TTR and age in COX analysis. These results greatly suggest the need for providing greater assistance to patients who take anticoagulant medications with the purpose of reducing self-medication and consequently, adverse reactions.Resumo em Inglês:
Abstract The study was aimed at assessing and comparing physicians’ and pharmacists’ attitudes and experiences with collaborative practices, along with the extent of barriers toward interprofessional collaboration in Iraqi healthcare settings. A descriptive, cross-sectional study was conducted among physicians and pharmacists in different healthcare settings in Baghdad, Iraq through an interview using a structured 3-part questionnaire, assessing the demographic characteristics, attitudes and barriers to interprofessional collaborative practices. A total of 384 participants were enrolled in this study. The physicians and pharmacists reported a significant positive attitudes towards collaboration, such as ‘’pharmacists are qualified to assess and respond to patients’ drug treatment needs’’ (69.8%, vs. 89.6%,; P=0.001);‘’pharmacists have special expertise in counseling patients on drug treatment’’ (59.9%, vs. 86%; P=0.001); ‘’physicians and pharmacists should be educated to establish collaborative relationships’’ (80.7%, vs. 100%; P=0.001), respectively. However, 57.3% of the physicians agreed about ‘‘lack or inadequate of pharmacists’ time to provide direct and effective patient care because of medications dispensing duties’’, while 56.8% of the pharmacists disagreed about this barrier (P=0.005). Both professions reported significant, positive attitudes and shared some barriers toward collaborative practices; however, there is a disagreement in some areas in which both professions would like more collaboration for better patient care.Resumo em Inglês:
Abstract Diabetes is a self-managed condition with knowledge, attitudes and practices that can influence the overall treatment and outcomes delay the complications of diabetes. However, the few reported studies published point out that: low education level, poor adherence to pharmacotherapy and diet recommendations, infrequent monitoring of blood glucose, and insulin dosage regimen are associated with higher hemoglobin levels. This study aimed to assess the knowledge, adherence medication, and complexity of pharmacotherapy in T1DM patients in Brazil. A cross-sectional study was conducted involving 156 T1DM patients who were attending in primary care. Logistic regression analyses were conducted to assess the variables associated with glycemic control. The overall assessments of T1DM patients for the glycemic control were bad (121, 77.6%). However, T1DM patients with high MedTake Test (OR=2.4, CI=1.1-5.7) and Morisky-Green Test (OR= 2.5, CI=1.1-6.1), and in the use of dosage insulin (>40 units, OR=0.3, CI=0.1-0.7) and postprandial glucose (100-125mg/dl, OR=3.8, CI=1.1-14.6) had better glycemic control compared to uncontrolled patients. Glycemic control in Brazilians adults with T1DM is low. We suggested the screening patients with low MedTake and Morisky-Green Tests, increasing patient knowledge as part of a complex intervention that may lead to substantially improved treatment outcomes in primary care.Resumo em Inglês:
Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1β, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties.Resumo em Inglês:
Abstract There is a global improvement in critical care services that leads to prolonged survival after ICU stay. This improvement has increased the demand for multidisciplinary critical care services beyond the ICU. Recently, efforts focused on the patient’s quality of life after ICU discharge and family involvement in their care. Most older adults who survive an ICU stay are challenged by complex medication changes following discharge, as are their caregivers. Limited literature addresses the standard of practice for medication management and critical care pharmacists’ involvement in post-ICU services. This narrative review describes the available literature that addresses medication management in post-ICU settings by critical care pharmacists and potential axes for future research. The included articles were articles published in English related to adult ICU survivors and addressed pharmacist involvement or medication management. The main findings summarize the most performed pharmacist services following ICU discharge, including medication reconciliation, full medication review, and adverse drug event preventative measures. This review concluded a lack of consensus about the standard model of post-ICU pharmacy services and the relationship of these services with long-term outcomes.Resumo em Inglês:
Abstract The use of Echinacea purpurea (EP), a plant native from North America, is widely diffused throughout the world, presenting many pharmacological applications, mainly for the treatment of infections of respiratory and urinary tracts. Due to the widespread commercialization of EP-based products, an effective evaluation of their pharmacological properties is essential to assure efficacy during clinical use. In this study, in vitro tests were performed to evaluate the antimicrobial activity of dried extracts of EP by the microdilution method. In addition, a phagocytosis model was employed to assess the immunomodulatory potential of the extracts. The increase in reactive oxygen species production, as well as the intracellular proliferation rate of Cryptococcus gatti after phagocytosis by macrophages in the presence of EP dried extracts were also evaluated. The analyzed samples showed no significant antibacterial activity; however, a slight antifungal activity was verified. Positive effects of EP extracts on the modulation of cellular immune response were observed in different experiments, indicating that this mechanism may contribute to the control and treatment of infections.Resumo em Inglês:
Abstract Rumex vesicarius hasbeen extensively used for the management of diabetes in the traditional system of medicine. The current study was designed to investigate antidiabetic and antihyperlipidemic effects of R.vesicarius and also to explore metabolomic profiling using UPLC-QTOF-MS. The effect of extracts was observed by checking the biochemical and histopathological parameters in diabetic rats. The results had shown a significant dose- dependent inhibition potential of aqueous extract of R. vesicarius seed against α-amylase and α-glucosidase along with significant inhibition in DPPH free-radical scavenging activity. Oral administration of R. vesicarius to diabetic rats significantly ( p< 0.05) ameliorated blood glucose level. It also improved the function of the liver and kidney as well as ameliorated dyslipidemia in diabetic rats. Histopathological examination of the treatment groups reversed the damage of the pancreas, liver, and kidney tissues confirming the antidiabetic efficacy of R. vesicarius. UPLC- QTOF-MS analysis of the extract revealed a total of 42 bioactive compounds, which might contribute to the antidiabetic activity. Based on our findings, we can conclude that R. vesicarius might be a promising candidate for the management of diabetes.Resumo em Inglês:
Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds.