Resumo em Inglês:

A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2-23.2 µg/mL) and PTP1B (IC50 = 2.9-21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

Resumo em Inglês:

The effect of solvent polarity on extraction yield and antioxidant properties of phytochemical compounds in bean seeds was studied. Seed flour of three varieties of bean was extracted in a series of organic solvents with increasing polarity (n-hexane, petroleum ether, chloroform, ethyl acetate, ethanol, acetone and water). Preliminary screening of phytochemicals showed the presence of tannins, flavonoids, cardiac glycosides, anthocyanins, terpenoids, carotenoids, ascorbic acid and reducing compounds in all extracts. One way analysis of variance (ANOVA) of results showed that extraction yield, phytochemical content and antioxidant properties were significantly influenced (p<0.05) by the polarity of extracting solvents. The regression analysis of data showed polarity-dependent second order polynomial variations in the extraction yield, phytochemical contents, antioxidant activity, reducing properties and free radical scavenging activity of each variety. Extraction in highly polar solvents resulted in high extract yield but low phenolic and flavonoid content as compared to non-polar ones. The polarity-dependent increase in total antioxidant activity and reducing properties indicates the extraction of strong antioxidant compounds in polar solvents. The study suggests the use of a combination of polar and nonpolar solvents to increase the extraction efficiency of phytochemicals with good antioxidant quality from the bean and other legume seeds.

Resumo em Inglês:

Vitis vinifera (black raisin) is commonly used in traditional medicine for the treatment of various ailments. In the present study, anti-oxidative and anti-cancer efficacy of oleanolic acid from ethyl acetate fraction of black raisins was evaluated and oleanolic acid was isolated without using of any chromatographic techniques and subjected to spectral assessment using UV-Vis spectrophotometer, 1H NMR, 13C NMR, MS and FT-IR for structural confirmation. Antiproliferative efficacy of oleanolic acid against human colon adenocarcinoma HCT-116 cells was assessed using cell viability assay. The minimum inhibitory concentration (IC50) was determined and found to be 40 µg/mL at 48h incubation. Furthermore, antioxidant property of oleanolic acid was analyzed using DPPH method (IC50 is 61.5µg/mL) by compared to standard antioxidants ascorbic acid, gallic acid, pyrogallol and butylated hydroxytoluene. Hence, the present study aims to establish the use of oleanolic acid as a potential therapeutic agent against human colon cancer.

Resumo em Inglês:

The aim of the present study was to characterize and evaluate nanoemulgel of snakehead fish powder (SFP) for the poorly water-soluble drug. SFP was formulated into nanoemulsion utilizing the best comparison of surfactant, co-surfactant, and oil. Diverse nanoemulsion components (oil, surfactant, and co-surfactant) were chosen based on solvency and emulsification capacity. SFP 0.1% loaded nanoemulsion which tested by stress-stability testing which carried out for all formulations and those that passed these tests were characterized for droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, and transmittance. After that, nanoemulsion was added with 1.5%, 2.0%, and 2.5% of HPMC in different concentrations and mixed until nanoemulgel form and evaluated for pH, viscosity, spreadability, and extrudability measurement. The results of this research showed that SF nanoemulsion produced clear, stable, and transparent formula having the transmittance value 99.87%. Mean droplet size and zeta potential of the optimized nanoemulsion (NE4) were found to be 98.6±0.93 nm (PDI 0.1±0.20) and -57.5±0.3 MV respectively. Meanwhile, the evaluation results of nanoemulgel (NEG) showed NEG1.5 gave pH 6.0, viscosity 210 cP, spreadability 5.8 g cm/s and extrudability 1.4 g/cm2. Otherwise, NEG2.0 and NEG2.5 had high viscosity and pH generating low spreading on the skin i.e. 3.9 g cm/s and 2.8 g cm/s respectively. The results of the evaluation and preparation stability test showed a good level of stability of NEG1.5 with the viscosity and pH by one way ANOVA which did not change significantly.

Resumo em Inglês:

Piroxicam (PRX) was determined in pharmaceutical capsules with differential pulse voltammetry (DPV) in a three electrode system consisting of a pencil graphite electrode (PGE) as working electrode, a Pt wire and a reference electrode of Ag/AgCl/KCl 3 M. An irreversible oxidation peak was observed in Epa c.a. 0.6 V, which correlates to the oxidation of PRX. The coefficient of linear correlation obtained was 0.9946, with limit of detection of 2.1 µM and limit of quantification of 4.7 µM. PGE assays showed good analytical performance compared to high performance liquid chromatography and spectrophotometry, showing the potential to be further developed and employed in quick and simple analyses.

Resumo em Inglês:

Diabetes Mellitus (DM) is a metabolic syndrome characterized by hyperglycemia. Chronic complications affect a number of organs, including the lungs. Cissampelos sympodialis Eichl (Menispermaceae) is a plant used to treat respiratory diseases. The aim of this study was to evaluate the effect of Cissampelos sympodialis extract (CSE) in lungs of diabetic rats. We used 30 Wistar rats divided into three groups: control group (CG), diabetic group (DG) and diabetic Cissampelos sympodialis treatment group (DTG). Diabetes was induced by streptozotocin (40 mg/kg i.v.). The CSE (400 mg/kg, po) was administered daily, during four weeks, beginning one week after the onset of DM. The treatment with CSE was not able to reduce blood glucose levels after streptozotocin injection. However, it was able to decrease cholesterol and triglycerides and prevent damage on pancreatic islets morphology. Additionally, morphological alterations such as alveolar septa loss, inflammatory infiltrate and fibrosis were seen in lung tissue of rats with DM, and treatment with CSE apparently reversed these histopathological findings. Thus, CSE treatment reduced the lipid profile and restored the lung architecture of diabetic animals by a mechanism independent of glycemia and which might be associated with the reduction of the damage on the pancreatic islets.

Resumo em Inglês:

Hepatocellular carcinoma is one of the most prevalent malignancies and a leading cause of cancer-related mortality worldwide. However, the therapies to prevent hepatocellular carcinoma are still limited and the emergence of drug resistance leads to the development of new anti-cancer drugs and combinational chemotherapy regimens. Our study was aimed to explore the anticancer effects of the essential oil extract (EEEO) from Euphorbia esula which has been widely used in traditional Chinese folk medicine and possessed potential cytotoxic effects in several human tumor cells. However, the mechanisms of EEEO-induced anti-proliferation and apoptosis have not been completely elucidated. In this study, EEEO was prepared by hydro-distillation and the main chemical component of EEEO was identified by GC-MS. HepG2 cells were treated with EEEO in vitro and then evaluated with respect to proliferation, apoptosis, and levels of reactive oxygen species (ROS) and apoptotic proteins. Our studies showed that EEEO decreased cell viability, elevated ROS levels, and induced apoptosis of HepG2 cells in a concentration- and time-dependent manner. Furthermore, Bcl-2 was down-regulated, while Bax was up-regulated in HepG2 after EEEO treatment. These results suggest that EEEO induced apoptosis of HepG2 cells and indicate that this apoptosis might be mediated by the mitochondrial pathway.

Resumo em Inglês:

The chlorogenic acid, rosmarinic acid, and caffeic acid contents in 100 selected plants were determined using reversed phase high performance liquid chromatography equipped with diode array detector. The optimum condition was 0.2% phosphoric acid in water (solvent A) and methanol (solvent B) as the mobile phase, which was set at 45% B for 20 minutes at a flow rate of 1.2 mL/min. The column temperature was maintained at 30 ºC and the detection wavelength was 325 nm. Among 100 selected plants, 39.64% contained all 3 compounds, 40.54% contained 2 compounds, 14.41% contained only 1 compound, and 5.41% could not detect any of the 3 compounds. The highest contents of chlorogenic acid, rosmarinic acid, and caffeic acid were found in Lonicera japonica flowering buds, Melissa officinalis leaves, and Coffea canephora seeds at the concentration of 9.900 ± 0.004, 19.908 ± 0.171, and 1.233 ± 0.003 g/100 g of dried plant, respectively.

Resumo em Inglês:

Parkinson’s disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson’s disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Resumo em Inglês:

Systemic fungal infections are a growing problem in contemporary medicine and few drugs are licensed for therapy of invasive fungal infections. Differences between fungi and humans, like the presence of a cell wall in fungal cells, can be explored for designing new drugs. (1,3)-β-D-glucan synthase, an enzyme that catalyzes the synthesis of (1,3)-β-D-glucan, a structural and essential component of the fungal cell wall, is absent in mammals and this makes it an excellent target for the development of new antifungal agents. Papulacandins are a family of natural antifungal agents targeting (1,3)-β-D-glucan synthase. In this study we describe the synthesis and biological evaluation of two new Papulacandin analogs as potential (1,3)-β-D-glucan synthase inhibitors.

Resumo em Inglês:

Cancer is one of the most prevalent diseases worldwide and the natural products could be a source of bioactive compounds. Passiflora mucronata (PM) belongs to a very known vegetal genus, although, there are no studies about cytotoxic activity or isolated compounds. Different extracts from PM were obtained by liquid-liquid partition (P), Soxhlet (Sox) and supercritical fluid (SFE1-5) extraction techniques, being compared concerning their yields, chemical profile and cytotoxicity. The Sox extracts showed the highest yields (6.03%: hexane; 2.51%: dichloromethane) followed by SFE (from 4.34 to 1.63%) and partitions (1.06 and 2.26%). The hexane partition (HP) showed the best cytotoxic activity against K562 cell line (IC50 = 18.72 µg.mL-1). From HP, the following compounds were identified and analysed its cytotoxic activities: β-amyrin (IC50 = 3.92 µg.mL-1), β-sitosterol (IC50 = 3.37 µg.mL-1), stigmasterol (IC50 = 3.31 µg.mL-1) and oleanolic acid. Stigmasterol induced about 75% of K562 total apoptosis. The compounds were tested against MA-104 cell line and the selective index (SI) attributed (SI >10 for all compounds). This indicates good selectivity to K562 cell line at the expense of MA-104. This is the first time, identifying those compounds to PM .

Resumo em Inglês:

The present study aimed at the evaluation of Passiflora coccinea (Aubl.) antioxidant and photo protective in vitro activities, looking forward to their application as antiaging or sunscreen agents in cosmetic formulations. Methanolic and glycolic leaf extracts were prepared by three methods: ultrasound assisted extraction (UAE, 30 min.), maceration at room temperature (72 h) and maceration at 30 ºC (72 h). The antioxidant activities of the extracts were measured by DPPH and ORAC-FL assays and they were incorporated into a cosmetic emulsion to have their sun protection factor (SPF) measured spectrophotometricaly. The antioxidant activity of the emulsions were measured by DPPH and ORAC as well. C-glycosyl-flavones were identified in the extracts by ESI-MS/MS, in comparision with standards. The UAE methanolic extract and the maceration at 30 ºC glycolic extract were submmited to HPLC-DAD analysis and isovitexin was quantifyed in both by a validated method. The methanolic extract antioxidant activity was independent of the extraction method, higher than reported for other species of Passiflora and detectable when incorporated into the emulsion formulation. Maceration at 30oC was the most suitable method for glycolic extraction and its antioxidant activity was lower than the value presented by the methanolic extracts. None of the extracts exhibited a SPF value. Isovitexin in the UAE methanolic extract was 12.67 times higher than the most active glycolic extract, aside of their similar chromatographic profiles. Although a SPF value was not detected, the results indicate that P. coccinea can be a potential new source of antioxidants for topical antiaging formulations.

Resumo em Inglês:

Rutin is a flavonoid compound obtained from different vegetables and fruits; specifically, it is found in the seeds of buckwheat and in fruit peels, particularly citrus. It is also an important constituent of red wine. Rutin exhibits various biological properties including antiviral, vasoprotective, anti-inflammatory, and anticarcinogenic activities. However, its antioxidant activity is the most well studied. Despite the potential for in vitro applications, rutin presents low oral bioavailability that affects its biological activities. Nanoparticles composed of polymers, protein, or lipids are of great importance in the pharmaceutical and nutraceutical areas due to their physicochemical properties, which improve the pharmacokinetics of the drug which is loaded within. This study presents the production of bovine serum albumin (BSA) nanoparticles containing rutin by nano spray drying. Nanoparticles were characterized in terms of mean particle size, size distribution, morphology, zeta potential, and drug content; as well as their antioxidant activity. The optimized spray-drying conditions produced spherical particles with a mean size of 316 nm, zeta potential of −32 mV, and encapsulation efficiency around 32%. Moreover, when antioxidant activity toward the ABTS+ radical was assayed, nanoencapsulation increased the IC50 of rutin by 2-fold. The nano spray-drying process proved to be suitable for the production of rutin-loaded BSA nanoparticles with potential antioxidant activity.

Resumo em Inglês:

This research aimed to investigate the antagonistic activity of the bacterial endophytes from Myanmar medicinal plants. Thirty-one bacterial isolates were isolated from Myanmar medicinal plants: Tinospora cordifolia (Wild.) Miers., Catharanthus roseus G. Don., Tectona hamiltoniana Wall. and Boscia variabilis Collett & Hemsl. (Capparaceae). Dual culture and agar well diffusion methods were used for antimicrobial assay. One endophyte from Catharanthus roseus and two bacterial isolates from Boscia variabilis Collett & Hemsl. (Capparaceae) had not only the antibacterial activity towards the human pathogenic bacteria but also the antifungal activity against the plant pathogenic fungi. From 16S rRNA sequencing, one strain from Catharanthus roseus G. Don. was Bacillus amyloliquefaciens DSM7 and two antagonistic strains from Boscia variabilis Collett & Hemsl. (Capparaceae) were Bacillus subtilis subsp. subtilis str. 168 and Bacillus amyloliquefaciens DSM7, respectively. The best medium for the maximum production of the bioactive compounds was Bacillus medium supplemented with the 4% of starch and 0.3% of peptone for B. amyloliquefaciens DSM7 and B. subtilis subsp. subtilis str. 168 showed the maximum antimicrobial compounds production when it was incubated in the medium amended with 3% of starch and 2% of peptone. The optimum conditions for the the maximum production of the antimicrobial compound were the medium pH of 6 at 35 ºC after two days of incubation for B. amyloliquefaciens DSM 7 and B. subtitlis subsp. subtilis str. 168 secreted the maximum concentration of the bioactive compounds at pH 7.5 and 35˚C on second day incubation period. In conclusion, the isolated endophytic bacteria showed the strong antimicrobial activity towards the pathogenic microbes and they could be used in medicine and agriculture as well.

Resumo em Inglês:

A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 µm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min−1. UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 ºC under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL−1; LOQ: 105 ng mL−1) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: tmax was 2.5h, Cmax was 56.5 µg mL−1, t1/2 was 8.2 h, AUC0-36 was 845.9 µg h mL−1. The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.

Resumo em Inglês:

We developed and validated a stability-indicating assay method for the simultaneous determination of enrofloxacin and piroxicam in combination and in the presence of degradation products. Reverse-phase high-performance liquid chromatography analyses were carried out on a Vertisep C18 column and acetonitrile-water (48:52 v/v, pH 3.0) mobile phase with a 1.00 mL min−1 flow rate. The efficient chromatographic separation of these drugs and their forced degradation products was achieved in less than 5min with a peak purity match factor higher than 950. The method used showed linearity in the concentration ranges of 0.25 to 16.0 µg mL−1 for enrofloxacin (r = 0.9997) and 0.125 to 8.0 µg mL−1 for piroxicam (r = 0.9999) as well as precision (relative standard deviation lower than 2%), accuracy (mean recovery 100 ± 2%), and robustness, according to ICH (International Conference on Harmonization) and AOAC (Association of Official Analytical Chemists) guidelines. This method can simultaneously determine the combination of these drugs in a veterinary formulation and separate the drug peaks from their forced degradation products. Additionally, its optimized chromatographic conditions can contribute to the quality control of this formulation in pharmaceutical manufacturing plants and minimize waste from the organic solvent.

Resumo em Inglês:

Two simple, selective and sensitive spectrophotometric methods were developed and validated for the determination of valganciclovir hydrochloride (VLGH) in pure drug and tablets. The first method was based on the reduction of iron(III) to iron(II) by VLGH and subsequent formation of iron(III)-ferricyanide complex (Prussian blue) in acid medium which was measured at 730 nm (method A). In the second method (method B), permanganate was reduced by VLGH to bluish green manganate in alkaline medium and the absorbance was measured at 610 nm. The absorbance measured in each case was related to VLGH concentration. The experimental conditions were carefully studied and optimized. Beer’s law was obeyed over the concentration ranges of 2.5-20.0 and 2.0-40.0 µg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 1.28×104 and 6.88×103 L mol-1 cm-1. The limits of detection (LOD) and quantification (LOQ) were 0.11 and 0.33 µg mL-1 (method A) and 0.21 and 0.64 µg mL-1 (method B). Within-day and between-day relative standard deviations (%RSD) at three different concentrations levels were < 2.4%, and the respective relative errors (%RE) were ≤ 3%. The proposed methods were successfully applied to the determination of VLGH in tablets, and the results confirmed that the proposed methods were equally precise and accurate as the official method.

Resumo em Inglês:

This study evaluated the incorporation of tetracaine into liposomes by RSM (Response Surface Methodology) and ANN (Artificial Neural Networks) based models. RCCD (rotational central composite design) and ANN were performed to optimize the sonication conditions of particles containing 100 % lipid. Laser light scattering was used to perform measure hydrodynamic radius and size distribution of vesicles. The liposomal formulations were analyzed by incorporating the drug into the hydrophilic phase or the lipophilic phase. RCCD and ANN were conducted, having the lipid/cholesterol ratio and concentration of tetracaine as variables investigated and, the encapsulation efficiency and mean diameter of the vesicles as response variables. The optimum sonication condition set at a power of 16 kHz and 3 minutes, resulting in sizes smaller than 800 nm. Maximum encapsulation efficiency (39.7 %) was obtained in the hydrophilic phase to a tetracaine concentration of 8.37 mg/mL and 79.5:20.5% lipid/cholesterol ratio. Liposomes were stable for about 30 days (at 4 ºC), and the drug encapsulation efficiency was higher in the hydrophilic phase. The experimental results of RCCD-RSM and ANN techniques show ANN obtained more refined prediction errors that RCCD-RSM technique, therefore, ANN can be considered as an efficient mathematical method to characterize the incorporation of tetracaine into liposomes.

Resumo em Inglês:

Traditional Chinese Herbal Medicine has been used to prevent and cure disease in China for thousands of years and has gained global interest in recent decades. The Erding formula is a Chinese Pharmacopeia (ChP)-listed herbal preparation used for treating sore throat, carbuncles and boils. Esculetin is a ChP quality control (QC) marker for these indications. A previous study found that a new indication, hyperuricemia, can be added to the Erding formula. Therefore, this study aimed to evaluate whether the traditionally used marker, esculetin, still has bioactivity for hyperuricemia, which is substantially different from the original indications. The study analyzed the quantity of esculetin by high-performance liquid chromatography, assessed the therapeutic effect of esculetin using animal model, and then characterized esculetin and its metabolites in serum via ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The results showed that the esculetin content in the aqueous Erding extract was 0.26±0.05% (w/w). Both the Erding extract and esculetin significantly reduced uric acid levels. Six metabolites of esculetin were identified in mice serum. This study revealed a rational scientific approach to prove esculetin is a reliable bioactive and QC marker for Erding formula in hyperuricemia treatment which contributed to ensure product quality and therapeutic efficacy.

Resumo em Inglês:

The relationship between the expression of HER2 and malignity of breast tumors has led to the generation of antibodies targeting HER2+ tumors. In addition, the expression of scFvs, as the smallest antigen-binding region of antibody containing two disulfide bonds in Escherichia coli often results in accumulating non-functional protein in the cytoplasm. A redox-modified strain of E. coli such as Origami (DE3) may facilitate the formation of proper disulfide bond in cytoplasm. The present study aimed to optimize the expression of anti-HER2 scFv in Origami and evaluate the influence of induction temperature, and host strain on the solubility of the protein. To this aim, chemicallysynthesized anti-HER2 scFv of Trastuzumab was cloned in pET-22b (+). The results demonstrated that anti-HER2 scFv is expressed in Origami, purified by using Ni-NTA column, and detected by anti-His antibody in Western blot analysis. The highest anti-HER2 scFv expression in Origami was achieved 24 h after IPTG induction (1 mM) at 37 ºC. Further, the total anti-HER2 scFv expression level was higher in BL21, compared to Origami strain. However, the ratio of soluble/insoluble forms of anti-HER2 scFv increased in Origami strain. Furthermore, higher soluble expression was achieved when the culture of recombinant Origami was conducted at lower temperature (25 ºC).

Resumo em Inglês:

Chagas disease is a serious public health problem in Latin America and, due to migration, in other non-endemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.

Resumo em Inglês:

This study evaluated the efficacy of combination therapy of secnidazole-diminazene aceturate (SEC-DA) in late treatment of dogs experimentally infected with relapsing strain of Trypanosoma brucei brucei. Fifteen dogs were randomly assigned to 5 groups (A - E) of 3 per group. Group A (uninfected untreated), B (infected untreated), C (infected and treated with DA (3.5 mg/kg) IM stat), D (infected and treated with secnidazole (SEC) (100 mg/kg) orally for 5 days and DA (3.5 mg/kg) IM stat), E (infected and treated with SEC (200 mg/kg) orally for 5 days and DA (3.5 mg/kg) IM stat). Dogs were infected intraperitoneally with 5 x 105 trypanosomes and treatment started 14 days post-infection. Data on parasitaemia, hematology and rectal temperature were recorded. Parasitaemia cleared within 3 days in all the SEC-DA treated dogs and there was no relapse parasitaemia. Parasitaemia did not clear in DA monotherapy dogs. All the SEC-DA treated dogs showed significantly (P < 0.05) higher leucocyte counts, red blood cell count, packed cell volume, hemoglobin concentration and lower rectal temperature than DA monotherapy. It was, therefore, concluded that SEC-DA combination is therapeutically more efficacious than DA monotherapy in the late treatment of T.b. brucei infection in dogs.

Resumo em Inglês:

Contrast-induced nephropathy (NIC) is directly related to increased morbidity and mortality, and its treatment and prevention might be achieved by the administration of antioxidant products. The juçara palmetto (Euterpe edulis Martius) has fruits rich in phenolic compounds, which are known for their antioxidant activity. This work aimed to evaluate the nephroprotective activity of E. edulis pulp in the NIC animal model. The collected fruits were pulped, their contents of polyphenols and anthocyanins were quantified, and their antioxidant activity were evaluated. The nephroprotective effects were determined based on iodine contrast induction and evaluated by biochemical and histological analyses. The results showed that E. edulis pulp was rich in polyphenols (811 ± 16.7 mg EAG/g) and anthocyanins (181.25 mg/100 g) and had very strong antioxidant activity, as demonstrated by the DPPH (2,2-diphenyl-1-picryl-hydrazyl) method, which revealed an antioxidant activity index (AAI) of 3.4, and the 2,29-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method, which revealed an IC50 of 0.59 ± 0.03 mg/mL. In the in vivo experiments, E. edulis pulp tended to provide renal protection and reduce renal dysfunction and tubular morphological lesions in mice after the induction of NIC, and these effects were obtained through the antioxidant activities of the polyphenols in the pulp.

Resumo em Inglês:

Serious health consequences can occur not only from acute exposure to environmental toxicants, but also from chronic exposures to minute quantities. Petroleum substances are widely distributed and used in huge amount, mainly as fuels. A total number of 45 males aged between 20 and 45 years participated in this study. The participants were divided in to two groups: The first group of 25 subjects worked at least 8hours/day in different oil product distribution companies in both Basrah and Thiqar Governorates-Iraq. The second group (control group) of 20 healthy individuals with age and weight matched with the test group and lived far away from hazardous exposure. Heavy metals levels in hair were measured by Atomic Absorption Spectrophotometer. Statistical analysis was performed using GraphPad Prism (version 6.0). Higher levels of lead and cupper were observed in the hair of subjects working in different oil product distribution companies compared to control group. Heavy metals evaluation in hair samples could be used as a good bioindicator of heavy metal exposure in occupational and environmental surveys for various populations for screening for heavy metals toxicity. In the present study high levels of heavy metals were observed in workers at different oil product distribution companies in Iraq.

Resumo em Inglês:

Present study was aimed to prepare and characterize fluconazole loaded nanostructured lipid carriers (FLZ-NLCs) for the treatment of fungal infections. Fungal infections are tremendously widespread and are the often faced dermatological condition worldwide. FLZ-NLCs was prepared by ultrasonication emulsion technique using stearic acid (SA) as solid lipid, castor oil as liquid lipid and tween 20 as a surfactant. The mean diameter of optimized FLZ-NLCs were found to be 359.15 ± 9.83 nm. The drug content and entrapment efficiency of NLCs was found to be 102.97 ± 7.45% and 87 ± 0.59%, respectively. In vitro drug release studies of FLZ-NLCs showed 37.34 ± 2.08% drug release over a period of 72 h. The above studies confirmed the prepared FLZ-NLCs may be useful for the treatment of fungal infections.

Resumo em Inglês:

The leaf extract of Annona squamosa L. has antibacterial, antidiabetic, antioxidant, and anticancerous activities. The present work aims to compare between liposomes and niosomes as carriers for A. squamosa extract to improve its transdermal bioavailability. Physical characterization for niosomes and liposomes was performed using: transmission electron microscope (TEM), scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). In addition, the encapsulation efficiency for A. squamosa in both carriers was evaluated and in-vitro drug release experiments were performed. The results proved the potential of both carriers to penetrate the outer layer of the skin (stratum corneum) which is considered as a strong barrier against the diffusion of many compounds through the skin. Moreover, the results pointed out that niosomes and liposomes lasted long time through the skin, which ensures the presence of antioxidant extract in the skin for prolonged periods. This would have a benefit of targeting free radicals in the skin. The encapsulation efficiency of liposomes for A. squamosa extract exceeded that of niosomes, however, niosomes demonstrated longer time of drug release through the skin. In conclusion, niosomes and liposomes are promising carriers for dermal delivery of the antioxidant extract Annona squamosa.

Resumo em Inglês:

In this study, twenty-two new [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (5a-n, 6a-h) were synthesized under microwave irradiation (MWI). The chemical structures of the compounds were elucidated by their IR, 1H-NMR, LC-MS, and elemental analysis. The compounds were tested for antinociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods in mice. The varying levels of antinociceptive activity of the compounds were compared with those of aspirin. Among these compounds, compound 5g and 5j were found to be significantly more active than the other compounds and the standard in the tests. Also, inhibitory effects of the test compounds on COX-1 and COX-2 activities were investigated. DuP-697 for COX-2 and SC-560 for COX-1 were used as reference standards.

Resumo em Inglês:

Breast cancer cell uptake of Gd-metal is investigated based on the formation of coordinate compounds of gadolinium and glucose (Glu) molecules in solution. The hypothesis is that glucose helps Gd-internalization by complex formations constituted of Gd3+ coordinate to m-glucose molecules, whose valence was complemented by Cl- anions. Such a proposal is an insight toward a metabolic-dependent contrast-agent for cancer and inflammation in magnetic resonance image. A solution was prepared based on anhydrous d-glucose and gadolinium chloride (Gd-Glu). Uptake assays for MDA-MB-231(c231) cells were elaborated collecting incubated c231-cells with Gd-Glu and measuring metal-uptake and their concentrations by Nuclear Activation Analysis (NAA). The ionic solution was studied using Direct-Infusion Electrospray Ionization Mass-Spectrometry (ESI-MS) to identify Gd-Glu interactions. Means and standard deviations of Gd-masses were 13.3±0.8 and 12.5±0.7µg, at 361.5 µg of Gd in 3mL Gd-Glu/PBS solution, in times of 30-50 min, equivalent to the concentrations of 13404±2104 and 11347±2742 µg.g-1 in dried cells. Such values were statistically higher than the control with metal presence. ESI-MS demonstrated the m/z-signals at 516, 552, 696, 923, attributed to positively loaded-species containing Glu, Gd+3 and Cl-. In conclusion, Gd-internalization was increased in aqueous solution due to the gadolinium-glucose coordination. Such findings drive the research to MRI with Gd-Glu complexes.

Resumo em Inglês:

The present study aimed to investigate the in vivo inhibitory effect of histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) combined with sorafenib on human hepatocellular carcinoma HCCLM3 cells. The nude mice transplanted with HCCLM3 cells were randomly divided into control, SAHA, sorafenib and SAHA+sorafenib groups. The nude mice in the later 3 groups were intragastrically administrated with SAHA (10 mg·kg-1·day-1), sorafenib (10 mg·kg-1·day-1) and SAHA (10 mg·kg-1·day-1) combined with sorafenib (10 mg·kg-1·day-1), respectively, for successive 20 days. Finally, the inhibition rate of tumor was measured. The expressions of MEK1/2, p-ERK1/2, Cyclin D1, Bcl-2, Bax, p53, MMP-2, MMP-9 and uPA in tumor tissues were determined. Results showed that, compared with SAHA and Sorafenib groups, in SAHA+sorafenib groups the inhibition rate of tumor was significantly increased (P < 0.05), the expression levels of MEK1/2, p-ERK1/2, Cyclin D1, Bcl-2, MMP-2 and MMP-9 and uPA protein in tumor tissues were significantly decreased, respectively (P < 0.05), and the expression levels of Bax and p53 protein were significantly increased, respectively (P < 0.05). In conclusion, compared with single drug, SAHA combined with sorafenib can enhance the inhibitory effects on HCCLM3 xenografts in nude mice.

Resumo em Inglês:

The effects of new derivatives of caffeine-8-thioglycolic acid (100 µM) on isolated rat brain synaptosomes, human neuroblastoma cell line SH-SY5Y and human recombinant MAOB enzyme (hMAOB) (1 µM) were evaluated. Most of the compounds, administered alone, didn’t show statistically significant neurotoxic effects on SH-SY5Y, when compared to the control (non-treated cells). Of all studied structures JTA-2Ox, JTA-11, JTA-12 and JTA-13 decreased cell viability. In combination with 6-hydroxydopamine (6-OHDA) (100 µM), only JTA-1 and JTA-2 revealed neuroprotective effects, stronger than those of caffeine. All compounds administered alone revealed, neurotoxic effects on synaptosomes, as compared to non-treated synaptosomes. JTA-1, JTA-2 and JTA-3 showed lowest neurotoxic effects and were investigated in a model of 6-OHDA-induced oxidative stress. In this model of neurotoxicity, only JTA-1 and JTA-2 showed statistically significant neuroprotective effect, by preserving the synaptosomal viability and the level of reduced glutathione. Inhibition of hMAOB, was revealed by JTA-1 and JTA-2. They inhibited the enzyme by 23% and 25% respectively, thus approaching the selegiline activity, which was 42%. The possible mechanisms of neuroprotection of JTA-1 and JTA-2 might be a result from the inhibition of hMAOB, which catalyze the production of neurotoxic p-quinone from 6-OHDA.

Resumo em Inglês:

The present work describes the development of a capillary electrophoresis (CE) method for the chiral discrimination of amlodipine (AML) enantiomers using cyclodextrine (CD) derivatives as chiral selectors. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector; and carboximethyl-β-CD (CM-β-CD) was selected for the enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors were varied at the same time to optimize the separation method. The optimized method (25 mM phosphate buffer, pH = 9.0, 15 mM CM-β-CD, 15 ºC, + 25 kV, 30 mbar/1 second, detection wavelength 230 nm) was successfully applied for the baseline separation of AML enantiomers within 5 minutes. Successful validation and application of the proposed CE method suggest its routine use in enantioselective control of AML in pharmaceutical preparations.

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Phosphodiesterases (PDE) are group of enzymes which catalyze the hydrolysis of cAMP and cGMP. Since these cyclic phosphate moieties worked as intracellular second messengers in numerous physiological processes, their inhibition can affect normal physiology of living system. NSAIDs are among the frequently prescribed medications, because of their efficacy as analgesic, antipyretic and anti-inflammatory agents. They are known to block cyclooxygenase pathway. In limited data NSAIDs has been shown anti-tumor potential, and phosphodiesterase inhibition has assumed to be one of the mechanism. To date no further evaluation being done. Further, NSAIDs are classified as cyclooxygenase inhibitors and phosphodiesterase inhibition can imprint its side effects. This study first time investigates the effects of NSAIDs on phosphodiesterase 1 inhibition. The activity against snake venom phosphodiesterase 1 was assayed on a microtitre plate reader spectrophotometer. Selective COX-2 inhibitor, celecoxib, exhibited a potent PDE1 inhibitory activity, at therapeutic doses, with an IC50 value of 29.4 µM. The findings of our study are indicative of new pharmacological actions of cyclooxygenase inhibitors. This article presents the PDE inhibitory properties as a new effects of already existing drugs. These additional effects could be potentially helpful for researchers to assess other physiological and pathological states.

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Metabolism of anabolic androgenic steroids is important for its physiological effects. The aim was to investigate the effects of finasteride (a 5α-reductase inhibitor - 5αR) on cardiac and mutagenic effects promoted by ND. Male Wistar rats were separated into three groups: CONT, received the vehicles of ND and finasteride (Peanut oil+Saline); DECA group, received ND (20 mg.kg.week-1, i.m.), and DECAF received ND and finasteride (100 µg.kg-1, i.p.), for four weeks. After, hypertrophy, cytokines and Angiotensin Converting Enzyme (ACE) activity was determined in heart. Bone marrow was used for micronucleus evaluation. Treatment with ND promotes increase in cardiac hypertrophy, ACE activity and disbalance among pro- and anti-inflammatory cytokines, and combination with finasteride worsened those effects. Association with finasteride ameliorates the toxic effects of ND on bone marrow cells, as was observed by a normalization of the number of micronucleate polychromatic erythrocytes and the mitotic index. Our data demonstrates that deleterious effects promoted by ND are depend, at least in part, of its metabolization. Also, inhibition of 5αR by finasteride present variated effects dependent on organ studied. It can promote increase on cardiac damage and a reduction on mutagenic effects of ND, which demonstrated that dehydronandrolone has diverse role on ND effects..

Resumo em Inglês:

Chronic Kidney Disease (CKD) patients usually require the use of anticoagulants for treatment or prevention of thromboembolic diseases. One such commonly used anticoagulant is enoxaparin. However, special attention is advised when using this drug for CKD patients because dosage adjustments may be needed. This prospective observational study was conducted in adult patients (> 18 years) with CKD stages 3 to 5 who were followed-up daily via prescriptions, medical records and laboratory tests. Enoxaparin doses, renal function and adverse drug events (ADEs) were thus monitored. Of the 87 ADEs identified in this study, 56 (64.3%) occurred in patients requiring enoxaparin prescription adjustment. Out of the 9 patients who had severe ADEs, 8 (88.9%) needed enoxaparin prescription adjustment. The results of this study suggest an overall increased risk of major bleeding and ADEs in patients requiring enoxaparin prescription adjustment. Further investigation of alternative dosing regimens in patients with CKD to maintain efficacy while reducing risks is imperative, as are studies on the utility of monitoring anti-factor Xa activity to guide dosing of enoxaparin. In addition, the role of clinical pharmacists in the management of CKD patients is crucial, as dose adjustments are often necessary.

Resumo em Inglês:

Laurus nobilis L. is a large shrub belonging to the Lauracea family. Its leaves are widely used for food seasoning as well as in folk medicine. Various studies have demonstrated the antiproliferative, antifungal and antibacterial effects of Laurus nobilis, but no studies have investigated the genotoxic effect of the aqueous extract of the plant. The objective of this study was to analyze the genotoxic potential of an aqueous extract of leaves, using the Allium cepa assay and mouse peripheral blood cell micronucleus test. The results showed that the extract did not have any genotoxic activity, but cytotoxic activity was observed in the two experimental models used. The extract had an antiproliferative effect, detected through the reduction of the mitotic index and the polychromatic/normochromatic erythrocyte (PCE/NCE) ratio. The tests also demonstrated a large number of cells undergoing apoptosis and with nuclear abnormalities related to cell death processes. These results can be explained by the presence of phenolic compounds, saponins, flavonoids and alkaloids, detected in the phytochemical analysis of the extract. Therefore, the extract from L. nobilis in the form generally used by the population does not pose risks related to its genotoxic potential, and also contains components with apoptotic and antigenotoxic potential.

Resumo em Inglês:

The functional significance of upregulation miR-34a in combination with albumin-bound paclitaxel nanoparticles in U251 glioblastoma cell line has been evaluated. The MTT assay determined that miR-34a and albumin-bound paclitaxel nanoparticles can reduce cell viability, but the combination of both factors has a stronger effect on cell viability. The application of qRT-PCR has demonstrated that the transduction of miR-34a could lead to exogenous upregulation of miR-34a level and downregulation of SURVIVIN. Moreover, treatment of U251 cells with miR-34a and nanoparticles together considerably inhibit SURVIVIN expression compared to miR-34a and nanoparticles alone. Flow cytometry showed that upon miR-34a overexpression cell cycle arrested in G1 phase, while treatment with nanoparticles increased the cell population in G2 phase. Upregulation of miR-34a along with treatment with nanoparticles elevated the number of cells arrested in G1/ G2 phases of the cell cycle. Expression of miR-34a with albumin-bound paclitaxel nanoparticles reduced cell viability, downregulated SURVIVIN and enhanced cell cycle arrest in G1/G2 phases. Thus, the upregulation of miR-34a with these nanoparticles are potential candidates therapeutic for glioblastoma cancer.

Resumo em Inglês:

Radiotherapy is often used for the treatment of cancer. However, it causes some side effects in patients. This study aimed to determine the hepatoprotective effects of Urtica dioica L. seed-extract (UDSE) in radiation-induced liver injury. Thirty-two male rats were randomly divided into 4 groups (n=8): control(C) group: no action was taken; radiation (R) group: irradiation was administrated at 5Gy single-fraction, radiation with UDSE(R+UDSE) group: irradiation was administrated at 5 Gy single-fraction and animals were fed pellets with 30 mL UDSE/kg; UDSE group: animals were fed pellets with 30 mL UDSE/kg. All of the experiments were performed in all of the groups over 10 days. Malondialdehyde (MDA) and reduced-glutathione (GSH) levels and superoxide-dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px), aspartate-transaminase (AST), and alanine-aminotransferase (ALT) activities were determined. Histopathological findings were also evaluated in liver tissues. SOD, CAT and GSH-Px activities and GSH levels in the serum and liver were significantly increased, while MDA levels decreased in the R+UDSE group compared with the R group (P<0.05). Moreover, AST and ALT serum activities in the R+UDSE group were lower than those in the R group (P<0.05). In addition, radiation induced degenerative/necrotic changes in the R group were significantly compensated in the R+UDSE group. The results showed that radiation increased oxidative stress and decreased antioxidant capacity, as well as degeneration in the liver. However, UDSE attenuated these degenerative changes.

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Polymyxins are a group of antibacterial substances and have remained the drugs of choice for treatment of resistant Gram-negative bacilli. Polymyxin B is administered by intravenous infusion and requires the reconstitution of lyophilized powder with 0.9% saline or 5% glucose solutions. To date, there is little information about polymyxin stability in different infusions solutions, especially at 40 ºC, a temperature that is recommended to study drug stability as it accelerates degradation reactions. Therefore, in this work an analytical method using LC-MS/MS was developed, validated and applied to determine the stability of polymyxin B diluted in 0.9% saline or 5% glucose solutions at 25 ºC and 40 ºC. The stability of polymyxin B solutions was evaluated during 72 hours. Polymyxin B1 and B2 were stable for 24 hours in saline (0.9%) and glucose solution (5%), however a significant degradation of polymyxin B1 and B2 was observed after 48 hours and 72 hours of assay. The reduction of polymyxin content was evidenced in both saline and glucose media, at room temperature as well as at 40 ºC. No significant differences in pH of polymyxin solutions (glucose or saline) were evidenced during stability assay.

Resumo em Inglês:

Ion-pairing liquid chromatographic method was validated for determination of ketoconazole in shampoo and cream samples as per ICH guidelines. The chromatographic conditions were carried out in the isocratic mode using a mixture of methanol and 8 mM sodium dodecyl sulfate (pH 5.5) in a ratio of 45:55 v/v %, as mobile phase. The flow rate was set at 1.0 mL min-1. Chromolith RP-18e (100×4.6 mm) was used as the analytical column with a fluorescence detection at an excitation wavelength of 260 nm and an emission wavelength of 375 nm. The average percentage recovery of shampoo A, shampoo B, shampoo C, cream A and cream B were 99.88, 97.06, 99.58, 96.77 and 97.26, respectively. The limit of detection was 0.12 mg L-1. The drug decomposition under acid degradation, base degradation and oxidative degradation were found to be in the range of 91.63-94.70% indicating that the drug is resistant towards acidic conditions. The drug decomposition under thermal condition and photolysis condition were found to be in the range of 69.05-87.15% and 47.31-66.83% respectively, indicating that the drug decomposition is more sensitive under photolysis conditions. This method is suitable for the quality control of ketoconazole in commercial shampoo and creams.

Resumo em Inglês:

This work describes the chemical characterization of extracts of Jatropha gossypiifolia (from Amazonia region) concerning the presence of phenolic and triterpenic compounds using Ultra High Perfomance Liquid chromatography coupled to Mass Spectrometry in Tandem (UHPLC-MS/MS) methods. The studied compounds belong to the most frequently found classes in medicinal plants (triterpenes, flavonoids, flavones, hydroxycinnamic acids, coumarins, catechins and stilbenes), which have been analyzed as chemical and bioactive markers in hydroethanolic and aqueous extracts. Several polyphenolic compounds identified herein are unprecedented in the scientific literature for this species. The chemical markers identified and quantified in the studied extracts of J. gossypiifolia were gallic acid, chlorogenic acid, catechin, caffeic acid, vanillic acid, p-coumaric acid, ferullic acid, rutin, quercitrin, 3-acetylcoumarin, trans-cinnamic acid, quercetin, luteolin, apigenin, kaempferol, chrysin. α-amyrin, β-amyrin and lupeol. As the majority compounds, (+)-catechin, p-coumaric acid, ferulic acid, luteolin, α-amyrin and β-amyrin were found to be present at mg kg-1 levels. J. gossypiifolia extracts presented a high in vitro activity against different reactive oxygen species (hydroxyl, peroxyl, and superoxide anion radicals). Several polyphenolic compound data presented herein are unprecedented in the scientific literature for this plant species. As a result, this plant can be a new source of bioactive molecules for therapeutic purposes.

Resumo em Inglês:

Verbena litoralis is a plant popularly known as “gervãozinho-do-campo” in Portuguese. It is traditionally used for stomach, liver and gallbladder problems, and as an anti-inflammatory and anthelmintic. The goal of this study was to determine the chemical composition of the crude extract obtained from the aerial parts of V. litoralis by Ultra High Performance Liquid chromatography coupled with Mass Spectrometry in Tandem (UHPLC-MS/MS); assess the anti-inflammatory activity of ethyl acetate fraction and of crude extract; and verify liver, kidney and pancreas damage. In this study, the chemical composition of the extract was identified via UHPLC/MS/MS, assessing the anti-inflammatory activity of the crude extract and the acetate fraction in an induction model of the granulomatous tissue, as well as given liver, kidney and pancreas damage markers. Chlorogenic acid, luteolin, caffeic acid, apigenin, p-coumaric acid, vanillic acid, ferulic acid and quercetin were quantified in the extract. After the seven-day treatment, the granuloma of the animals treated with the plant extract and fraction presented values very close to the positive control (nimesulide). The V. litoralis crude extract and ethyl acetate fraction show anti-inflammatory activity similar to the nimesulide without evidence of liver, kidney and pancreas damage, which attributes the plant’s pharmacological action to the flavonoids found.

Resumo em Inglês:

In the present study, a series of novel 5,7-diisoprenyloxyflavone derivatives were designed, synthesized, and evaluated for their antibacterial activity. Most of these compounds displayed significant antibacterial effects against Gram-positive bacteria, especially against strains of multidrug-resistant clinical isolates. Compounds 4c, 4g, 4i, 4j, 4k, 4l, 4n, 4q and 4t showed high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentrations of 4.0-20 µM. Compound 4k showed the most potent activity among these compounds against all multidrug-resistant clinical isolates tested. Unfortunately, none of the compounds were active against Gram-negative bacteria at the doses of 24-164 µM.

Resumo em Inglês:

Failure on the water treatment poses hemodialysis patients at risk of injury and death. Identifying if the patients are exposed to water quality related microbiological risks is an important objective to reduce the mortality for chronic renal patients and is the main issue of this study. We evaluated the microbiological water quality used by 205 dialysis services in São Paulo State, Brazil between 2010 to 2016. The study included heterotrophic bacteria count, total coliforms research, and bacterial endotoxin determination in 1366 dialysis water samples. The number of unsatisfactory clinics for at least one microbiological parameter decreased 16.0% between 2010 to 2015 but increased 57.2% in 2016. In 2010, the most frequent unsatisfactory parameter was related to heterotrophic bacteria count (54.8%) followed by endotoxin determination (45.2%). However, in 2013 an opposite situation was observed: endotoxin determination as the parameter of the higher incidence of nonconformities. Total coliform was verified at a lower frequency. We highlighted the importance of regular monitoring of dialysis water quality to prevent infections caused by dialytic procedures and to ensure that the water is a safe component of the treatment.

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An electrically-assisted microextraction method called electromembrane extraction, followed by a simple high performance liquid chromatography and ultraviolet detection was developed and validated for determining phenobarbital in biological samples. The major parameters influencing the electromembrane extraction procedure including solvent composition, voltage, pH of acceptor and donor solutions, salt effect, and time of extraction were evaluated and optimized. The drug was extracted from the donor aqueous sample solution (pH 9) to the acceptor aqueous solution (pH 13). The donor and acceptor phases were separated by a hollow fiber dipped in 1-octanol as a supported liquid membrane. A voltage of 40 V during 20 minutes was applied as the driving force. The enrichment factor was obtained >51 which enhanced the sensitivity of the instrument. Limit of detection and limit of quantitation were 7.5 and 25 ng/mL, respectively. The method was linear over the range of 25-1000 ng/mL for phenobarbital (R2 >0.9998) with repeatability (%RSD) between 0.4% and 6.8% (n = 3). The proposed method was successfully applied to human plasma and urine samples with relative recovery of 70-80% and %RSD < 6.8%.

Resumo em Inglês:

Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twenty-four healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected.

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The para rubber tree (Hevea basilensis) is an economically important tropical tree species that produces natural rubber, a valuable industrial raw material. Innovative products that are derived from by-products from the rubber production process, such as seeds, are important for the sustainability of the para rubber industry. Therefore we subjectively assessed para rubber seed oil for its makeup-removal efficacy and developed it into a makeup cleansing product with appropriate quality control measures for the cosmetic industry. The makeup-removal efficacy of para rubber seed oil was analyzed using a validated UV-Vis spectroscopy, which indicated that the oil removed 86.21 ± 2.48% of liquid foundation [relative standard deviation (RSD) = 2.88%]. Therefore, we developed stable makeup removers containing 40-70% para rubber seed oil. Bio-oil removers containing 50% and 60% oil had the best appearance and texture and were subsequently evaluated for their makeup-removal efficacy. The bio-oil remover with the higher oil content was significantly better at removing makeup (95.26 ± 0.97% removal by the 60% oil compared with 73.88 ± 3.97% removal by the 50% oil). To conclude, para rubber seed oil is a promising new bio-oil for the cosmetic industry, which broadens consumers’ choices of bio-oil makeup removers. We believe that the manufacture and quality control of this innovative and efficient makeup remover are feasible on an industrial scale.

Resumo em Inglês:

Snake bites are a serious health hazard occurs throughout the world especially in tropical countries like India. Anti-Snake Venom Serum is the only remedy available to treat snake bite victims successfully till date. Infusion of ASV may lead to adverse reactions ranging from severe itching of the skin, hives to potentially serious allergic reactions. Considering all above difficulties research workers all over the world is constantly in search of a cheap and readily available easy formulate remedy for treating snake bite victims. In present study aqueous extract of Rauvolfia serpentina root was checked for the antidote properties against Naja naja venom by in vitro and in vivo methods. Various in vitro neutralization tests like Acetyl cholinesterase, Protease and ATPase activity of Naja naja venom were carried out and the root extract was neutralized all the toxic effects induced by the venom. The in vivo assessment of venom lethality (LD50) of Naja naja venom was found to be 0.301 µg. The aqueous root extract was effectively neutralized the venom lethality and effective dose (ED50) was found to be 12.88 mg/ 3LD50 of Naja naja venom. LC-MS analysis from root extract of Rauvolfia serpentina was done for confirmation of the bioactive compounds.

Resumo em Inglês:

The objective of this study was to determine specific combination of pharmaceutical excipients that lead to formulation of efficient nebivolol hydrochloride SMEDDS and its subsequent formulation into IR-SET (Immediate release- Self emulsifying tablet) which will enhance its solubility and dissolution. Solubility and Pseudo-ternary phase studies were carried out to identify the excipients showing highest solubility and to identify the zone of microemulsion with selected ingredients. Liquid-SMEDDS (L-SMEDDS) were optimized for Concentration of oil(X1) and Smix(X2) and formulated using a combination of Kollisolv GTA as oil, Tween 80 as surfactant and propylene glycol as co-surfactant which gave smaller droplet size(Y1) 55.98nm , Emulsification time (Y2) 16±1.5 s,% transmittance (Y3) 99.94±0.47%. Neusilin US2 was used as solid carrier for solidification of L-SMEDDS in to Solid-SMEDDS (S-SMEDDS) by adsorption technique. IR-SET of nebivolol were formulated with S-SMEDDS and optimized for the concentration of binder (X1) (PVP K30) and superdisintegrant (X2) (KOLLIDON CL) which showed low Disintegration time (Y1) (92±0.5s) and low Friability(Y2)(0.424±0.03%). Also the DSC and XRD data revealed the molecular state of the drug in S-SMEDDS. The extent of in-vivo drug release and ex-vivo diffusion values from L-SMEDDS and IR-SET was much higher than pure drug and marketed tablet. In conclusion, the results showed potential of SMEDDS to improve solubility and thus the bioavailability.

Resumo em Inglês:

The repositioning of approved drugs is atopic of interest for the academy and the pharmaceutical industry. The synergistic combination of these drugs can be successful in the treatment of infections caused by resistant bacteria. This study aimed to assess the in vitro synergistic antibacterial activity of sertraline and disulfiram and their interaction with ciprofloxacin and sulfamethoxazole/trimethoprim. We determined the minimum inhibitory concentration, the minimum bactericidal concentration and the fractional inhibitory concentration index. Eighteen bacterial strains were used, being nine American Type Culture Collection reference strains and nine multidrug resistant clinical isolates. Synergy was detected between sertraline and disulfiram against a strain of Staphylococcus aureusATCC 25923 and a clinical isolate of S. aureus. When associated to sulfamethoxazole/trimethoprim and ciprofloxacin, sertraline and disulfiram showed eight synergistic events, which occurred against three different standard strains and two multidrug resistant clinical isolates. When the minimum bactericidal concentration was determined, the bactericidal activity of sertraline was enhanced with disulfiram. Our results suggest that these drugs, widely used to treat depression and chronic alcoholism, have antibacterial potential individually, in association, and combined with antimicrobials, what makes their repositioning a promising therapeutic alternative for the effective treatment of infections caused by multidrug resistant bacteria.

Resumo em Inglês:

This study investigated the effect of ionic liquid (IL)-microwave assisted extraction (MAE) on γ-oryzanol extraction from rice bran (Oryza sativa L.). The conditions included the concentration of IL, liquid (IL)/solid (sample) ratio, extraction time, and microwave power. The use of 1-butyl-3-methylimidazolium ([Bmim]BF4) as a selected solvent in IL-MAE method was developed for extraction of γ-oryzanol from rice bran. The Box-Behnken design on four factors with response surface methodology (RSM) was used to optimize the experimental conditions. The optimum conditions for the MAE were a [Bmim]BF4 concentration of 0.7 M, liquid/solid ratio of 15 mL/g, extraction time of 10 minutes, and 30% microwave power with a γ-oryzanol value of 0.41 mg/g. The experimental values agreed with those predicted by the RSM models. A microplate reader method was used to determine the IC50 value in tyrosinase inhibitory activity of the extract. An IC50 value of the extract obtained from IL-MAE was 1240 µg/mL. This study suggests that IL-MAE is suitable for the extraction of γ-oryzanol from rice bran and that under the optimum conditions the extract has low activity as a tyrosinase inhibitor.

Resumo em Inglês:

Melatonin (MLT) is a strong free radical scavenger that protects the body from the deleterious effects of excess oxidants. Synthesis of MLT analogue compounds with antioxidant potency has recently attracted the interest of researchers. In general, the strategy consists of modifying the groups in the different sites of the indole ring or replacing the indole ring with an analogue. As part of our ongoing research, the antioxidant capacity and cytotoxicity of newly synthesized MLT analogue naphthalene derivatives were evaluated. The radical scavenging activity was tested by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Most of the synthesized compounds showed significant antioxidant activity in comparison to MLT. The structure-activity relationship was identified. The in vitro cytotoxic effects of the synthesized compounds were also investigated in CHO-K1 cells using the MTT assay.

Resumo em Inglês:

This work presents the physicochemical properties of the prepared lac lakes. The study revealed the stability, cytotoxicity and use of lac lake pigment as a cosmetic colorant. SEM, XRD and DSC were used to study the characteristics of the lac lakes.. The color stability of lac dye and its lakes was investigated at ambient temperature and at 45 °C, in sunlight,fluorescent light and darkness, for 3 months. Cytotoxicity on human dermal skin fibroblast cell lines was tested using MTT assay and the use of the lakes as a colorant in lip color product was studied. Different metal salts resulted in lac lakes of different shades and appearance. SEM, XRD and DSC results indicated that the morphology and structure of lac dye were changed after reacting with metal salts which support the coordination of metal ion with lac dye. The lac lakes were not cytotoxic to human dermal skin fibroblast cells (0.78-100 µg/mL). Lac lakes exhibited less alteration of color shade over acidic and basic conditions when compared with the lac dye itself. Additionally, the lake pigments displayed better color stability than lac dye and produced an orange-brown shade of lip color product. The results suggest that lac lake pigments have good potential for use as cosmetic colorant.

Resumo em Inglês:

Resumo Amiodarone hydrochloride is one of the most important drugs used to treat arrhythmias. The USP monograph for amiodarone hydrochloride describes an HPLC method for the quantification of seven impurities, however, this method shows problems that result in unresolved peaks. Moreover, there is no monograph for tablets in this compendium. Thus, a stability indicating HPLC method was developed for the determination of amiodarone, its known impurities and degradation products in tablets. A detailed forced degradation study was performed submitting amiodarone API, tablets and placebo to different stress conditions: acid and alkaline hydrolysis, oxidation, metal ions, heat, humidity, and light. Amiodarone hydrochloride API was susceptible to degradation in all stress conditions. The tablets also showed degradation in all environments, except in acidic condition. The analytes separation and quantification were achieved on an Agilent Zorbax Eclipse XDB-C18 column (100 x 3.0 mm, 3.5 µm). The mobile phase was composed of 50 mM acetate buffer pH 5.5 (A) and a mixture of methanol-acetonitrile (3:4, v/v) (B) in gradient elution. The method was validated in the range of 350-650 µg/mL for assay and 10-24 µg/mL for impurities determination. Therefore, this method can be used both for stability studies and routine quality control analyses.

Resumo em Inglês:

Currently, the use of natural compounds obtained from plants tremendously increased due to their promising therapeutic properties. The aim of this study was to formulate a stable emulgel formulation loaded with Cinnamomum tamala (CT) extract. The antioxidant activity of plant extract was determined by DPPH inhibition assay. The extract was successfully loaded into an emulgels using different concentrations of carbopol-940, liquid paraffin, emulsifying agents and preservatives. Preliminary stability study was performed of 17 CT emulgel formulations at accelerated temperature of 50 °C for 2-months. Organoleptic evaluation, centrifugation, globule size, pH, electrical conductivity and rheological studies were performed for a period of 90-days at different temperature including 8, 25, 40 and 40 °C ±75% RH. The CT extract showed promising antioxidant activity of about 81%. On the other hand, the CT loaded emulgel formulation displayed high physical stability at all tested conditions of temperature and time. However, slight decrease in pH and minimum increase in conductivity was observed at 40 and 40 °C±75% RH. The rheological examination of CT emulgel indicated the flow index values of all the samples kept at different temperatures were less than 1, demonstrated non-newtonian and pseudo-plastic nature of CT emulgel. Taken together, the CT emulgel formulation has been evinced to be an excellent addition in the field of topical formulations.

Resumo em Inglês:

In Turkey, Helichrysum genus is represented by 26 taxa belonging to 20 species in Turkish flora of which 14 ones are endemic to Turkey. The aerial parts of Helichrysum plicatum subsp. plicatum are used kidney stones, kidney and stomach ailments. The extraction procedures and solvents are important step in processing of bioactive constituents from the plant materials. Therefore, the aim of this study was to evaluate in vitro antioxidant, antimicrobial, anti-urease, anticholinesterase and in vivo anti-inflammatory activities of Helichrysum plicatum subsp. plicatum different extracts. In addition, the phenolic characterization of the Soxhlet and maceration methanol extracts which showed significant antioxidant, anti-urease, antimicrobial, anti-inflammatory and anticholinesterase activities were performed by HPLC-DAD and LC-MS/MS. In the present study, the Soxhlet methanol extract exhibited strong antioxidant, antimicrobial and anticholinesterase activities than other extracts. The maceration methanol extract showed the strongest anti-urease activity. The Soxhlet methanol and maceration methanol extracts showed in vivo anti-inflammatory activities very close to each other. As a result of this study, chlorogenic acid, dicaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, naringenin-O-hexoside and isoquercitrin compounds were analysed in plant. Therefore, it is thought that methanol extracts can be used as a natural source in the future for food and pharmaceutical industries.

Resumo em Inglês:

Danofloxacin is a veterinary fluoroquinolone used to treat respiratory and gastrointestinal diseases of birds, pigs and cattle. The literature reviewed shows some analytical methods to quantify this fluoroquinolone, but microbiological and biological safety studies are limited. The analytical methods were validated by the Official Codes. The LC-DAD method was developed and validated using an RP-18 column, mobile phase containing a mixture of 0.3% triethylamine (pH 3.0) and acetonitrile (85:15, v/v). The microbiological assay was performed by agar diffusion method (3 x 3) and Staphylococcus epidermidis as a microorganism test. Forced degradation studies were performed in both methods. The minimum inhibitory concentration (MIC) was performed by test microdilution and toxicity studies were evaluated using in silico study, cell proliferation, cell viability test, micronuclei and comet assay. LC and a microbiological assay proved linear, accurate, precise, and robust to quantify danofloxacin, but only the LC method showed selectivity to quantify the drug in the presence of its degradation products. These results demonstrate that the LC method is suitable for stability studies of danofloxacin, but a microbiological assay cannot be used to quantify the drug due to the biological activity of the photoproducts. Ex-vivo cytotoxicity and theoretical and experimental genotoxicity were also observed.

Resumo em Inglês:

Tanacetum balsamita locally called Shahesparam is an aromatic plant that grows widely in Azerbaijan Province, Iran. Due to the widespread use of T. balsamita as a pain killer and relief of inflammatory based disorders in Iranian folk medicine and considering the high content of essential oil in T. balsamita aerial parts, we were prompted to investigate the anti-nociceptive and anti-inflammatory properties of T. balsamita essential oil (TBEO) for the first time. The carrageenan-induced Paw Edema was used for inflammation evaluation in rat, and hot-plate method was used for pain assessment in mice. Different doses of TBEO were administered. Morphine and Mefenamic acid were used as the standard drugs in anti-nociceptive and anti-inflammatory evaluation tests, respectively. TBEO (100 mg/kg) showed significantly anti-nociceptive activity in hot-plate test. The anti-inflammatory activity of TBEO was found to be more than mefenamic acid. The studied oil was analyzed by GC and GC-MS. The major component of the oil was characterized as carvone (39.8%) which might be responsible for the observed activities. The results suggested that TBEO possessed biologically active constituents that had significant analgesic and anti-inflammatory effects which support the ethno-medicinal claims of the plant application in the management of pain and inflammation.

Resumo em Inglês:

Cardiovascular diseases are the main source of death and morbidity in developed and developing nations. Animal models are required to propel our understanding of the pathogenesis, increase our knowledge, disease progress, and mechanism behind cardiovascular disorder, providing new approaches focused to improve the diagnostic and the treatment of these pathological conditions and additionally to test various therapeutic ways to deal with tissue regeneration and re-establish heart working following damage. A perfect model framework ought to be reasonable, effectively controlled, reproducible, and physiologically illustrative of human disease, show cardinal signs and pathology that resembles after the human ailment and ethically stable. The decision of selection of animal model should be considered precisely since it influences exploratory results and whether results of the research can be sensibly matched with the human. In this way, no specific technique splendidly reproduces the human disease, and relying upon the model, extra cost burden, resources, infrastructure and the necessity for technical hands, should also be kept under consideration. Here we have discussed and compiled various methods of inducing myocardial infarction in animals, basically by surgery, chemicals and through genetic modification, this may benefit the researchers in getting a complied data regarding various methods through which they can induce myocardial infarction in animals.

Resumo em Inglês:

It was aimed to investigate the radioprotective activity of Urtica dioica L. seed extract (UDSE) in the whole blood and liver of radiation-administered rats, both biochemically and immunohistochemically. 32 rats were divided into 4 groups (n:8). Control group (C): no administration for 10 days. Radiation group (IR): fed pellets for 10 days after exposure to radiation. Radiation + UDSE (IR+UDSE) group: exposed to radiation and fed UDSE for 10 days. UDSE group (UDSE): fed UDSE for 10 days. Radiation (5Gy) was given as a single fraction. 8-hydroxy-2-deoxyguanosine (8-OHdG) and deoxyguanosine (dG) levels were analyzed by biochemical method and glutathione peroxidase 1 (GPx-1) analyses were performed by immunohistochemical method in the liver and blood tissues of the rats. The increased 8-OHdG rates and decreased GPx-1 immunoreactivity was observed in the IR group. Those parameters were ameliorated in the IR+UDSE group when compared to the IR group. UDSE is likely to be a valuable radioprotector against the harmful effects of radiation.

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Parkinson disease is a neurodegenerative disorder characterised by the cardinal symptoms of stiffness, resting tremor, slowness (bradykinesia) and reduction of movement (hypokinesia). Involvement of oxidative damage has been reported in the pathophysiology of Parkinson disease and its related complications. The purpose of this study was to examine the effect of daidzein to quench the free radicals produced as a result of the increased oxidative stress in Parkinson disease.Parkinson disease is induced by administration of reserpine (5 mg/kg/day, i.p) for 5 consecutive days. The symptoms of PD such as tremors, akinesia and rigidity were evaluated. The effect was evaluated by assessing various behavioral parameters (grip strength and locomotor activity), biochemical parameters (lipid peroxidation, and reduced glutathione), as well as histopathological parameters in brain tissue. Daidzein (an antioxidant) was administered at the dose of 50 and 100 mg/kg, p.o. once daily for 5 days. Reserpine significantly causes tremor, rigidity, akinesia and oxidative damage which were reversed by daily administration of daidzein when compared toreserpine group. There was a significant histological improvement in the neuronal degeneration in brain tissue with daidzein. So, the results indicated the protective effect of daidzein against PD.

Resumo em Inglês:

Myrcia hatschbachii D. Legrand (Myrtaceae) is a native and endemic species from Brazil. This study investigated the essential oil composition, phytotoxic potential, in vitro toxicity, antioxidant properties and antibacterial activity of species. Chromatographic analysis of essential oil identified trans-calamanene, (E)-caryophyllene and spathulenol as major components. Antioxidant capacity was determined by the DPPH• scavenging method and phosphomolybdenum complex formation assay. Antibacterial activity was evaluated using the Minimal Inhibitory Concentration test, demonstrating that the essential oil was active toward Enterococcus faecalis and Staphylococcus aureus. Phytotoxic activity of essential oil was analyzed by testing interference on germination and growth of Lactuca sativa, demonstrating significant inhibition of the hypocotyls and radicles of seeds. Preliminary toxicity studies were determined using Artemia salina, resulting in an LC50 of 409.92 µg/mL, and through hemolytic activity. The results of the phytotoxic activity point to a possible application for Myrcia hatschbachii in the development of natural herbicides and the in vitro toxicity assays suggests the performance of antitumoral activity tests, having in mind the prospection of antineoplastic drugs.

Resumo em Inglês:

Obesity represents a major challenge to the pharmaceutical community due to the minimal availability of anti-obesity drugs and the drawbacks of current weight-loss agents. The study described herein presents lupine oil, in two pharmaceutical formulations, as a potential anti-obesity agent via its effect on different physiological, biochemical, and hormonal parameters. Rats were divided into two groups; one group was continued on a standard commercial rodent diet and served as the non-obese control. The other group was fed a high-fat diet for 7 weeks to prepare an obese rat model. Then, the obese rats were divided into groups to receive 100 mg/kg of the crude lupine oil or nanoemulsion for 10 or 20 days. Lupine oil showed a potent body weight-reducing effect and improved insulin resistance. The oil altered obesity-induced hyperlipidemia and it enhanced the leptin/adiponectin/AMPK hormonal system in epididymal fat, serum, and liver, to which all the above physiological activities could be attributed. The nanoemulsion formulation of lupine oil significantly amplified the activity for all the above physiological and hormonal parameters when compared to the crude oil formulation. Lupine oil nanoemulsion could be used as a potential drug against diet-induced obesity.

Resumo em Inglês:

This study was conducted to evaluate the effect of extracts of Passiflora edulis Sims leaves on the oxidative metabolism of rat peritoneal neutrophils using a model of acute inflammation. The extract was obtained by maceration in 70% ethanol, evaporation under reduced pressure and lyophilisation. Total phenolic content (TP) was determined by the Folin-Ciocalteu assay. The P. edulis extract, in different doses, was administered by gavage 1 h prior to inflammation induction by carrageenan (8 mg/kg, i.p.); five hours later, the neutrophils were obtained by intraperitoneal lavage. The tests performed in neutrophils were cytochrome C and chemiluminescence assay as well as myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. The administration of the extract reduced the number of neutrophils recruited to the site of inflammation; however, the extract did not alter the activity of NADPH oxidase as well as SOD activity in these cells. The MPO and CAT activities in peritoneal neutrophils of rat treated with extract was lower than in the control group, and the GPx activity was increased. Based on the experimental model utilised, the anti-inflammatory potential of P. edulis leaf extract could be related to the presence of phenolic compounds in the extract.

Resumo em Inglês:

Amphotericin B is a broad spectrum antifungal agent used to treat fungal infections. Organogel is a semisolid preparation in which the apolar phase gets immobilized within spaces of the three-dimensional structure. The current study aimed at the formulation and comparative evaluation of sorbitan monostearate organogels and pluronic lecithin organogels (PLO). Different compositions of span 60 based organogels were prepared by varying the concentrations of the span 60 and PLO gels were prepared by varying the concentration of Pluronic F 127. The developed organogels were subjected to various characteristics such as pH, viscosity, spreadability, extrudability, and drug release studies. The optimized formulations were evaluated against Candida albicans and carried out ex vivo release study. The optimized formulation was selected from span 60 based organogels, and pluronic lecithin organogels were S1 and P1, respectively. The optimized formulation (S1) showed effective inhibition against Candida albicans. The skin irritation test was carried out on albino mice for optimized formulations and results showed that no irritation to the skin. Based on the results, organogels prepared by sorbitan monostearate showed better antifungal activity, and also all the formulations were found to be stable and safe throughout the study period.

Resumo em Inglês:

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable.

Resumo em Inglês:

Psychotria fractistipula L.B.Sm, R.M. Klein & Delprete (Rubiaceae) is found in the existing Atlantic Forest in the South of Brazil, in the Paraná and Santa Catarina States. The members of Rubiaceae are characterized chemically by the presence of alkaloids, some pharmacological properties of which include antifungal, antibacterial, analgesic, antioxidant, antimutagenic, and antiviral activities. In this study, we report the results of anatomical, morphological, and histochemical analyses of the leaves and stems of the Rubiaceae family member, P. fractistipula. The anatomical analysis involved of light microscopy and scanning electron microscopy. Morpho-anatomical and histochemical characterization were made using standard methodology. The isolated compounds were identified by Nuclear Magnetic Resonance spectroscopic analysis. The following structures are highlighted as the distinctive features of the species: presence of petiolate leaves and a petiole base, leaf blade with smooth cuticle on both surfaces, paracytic stomata, and, dorsiventral mesophyll and presence of trichomes on the leaves and stems. Phytosteroids, identified as β-sitosterol and campesterol, were observed in the hexane fraction of the stem. Future studies should focus on the isolation of other fractions of interest and their characterization through specific biological and cytotoxicity assays.

Resumo em Inglês:

Given their relationship with metabolic syndrome and systematic inflammatory diseases, the pathogenesis of hypertension, hyperglycemia, and hyperlipidemia is closely related. To explore the common genes among these three conditions, spontaneous hypertensive rats (SHR), spontaneous diabetic Goto-Kakizaki rats (GK) and hyperlipidemia rats (HMR) were reared for experiments. Gene array was used to identify the genes of SHR, GK and HMR compared with normal Wistar rats using TBtools software. First, real-time PCR was applied to verify these genes, and Cytoscape software was used to construct networks based on the National Center for Biotechnology Information (NCBI) database. Second, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis was performed to classify the genes. Visualization and Integrated Discovery (DAVID) database and Gene Ontology database were used to explore the biological function. Finally, Onto-tools Pathway Express was used to analyze the pathways of shared genes. Importantly, upregulated common genes, such as Bad, Orm1, Arntl and Zbtb7a, were used to construct a network of 150 genes, while downregulated genes, such as Mif and Gpx1, formed a network of 29 genes. Interestingly, the networks were involved in various pathways, such as insulin signal pathway, endometrial cancer pathway, circadian rhythm pathway, and pancreatic cancer pathway. We discovered common genes of SHR, GK and HMR compared with normal Wistar rats, and the association of these genes together with biological function were preliminarily revealed.

Resumo em Inglês:

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

Resumo em Inglês:

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen.

Resumo em Inglês:

Angiogenesis is the formation of new blood vessels from preexisting vasculature. Uncontrolled angiogenesis is associated with progression of several ocular pathologies, such as diabetic retinopathy and macular degeneration. Thus, the inhibition of this process consists in an interesting therapeutic target. Corosolic acid (CA) is a natural derivative of ursolic acid, found in many medicinal herbs and exhibits numerous biological properties, including the antiangiogenic activity. The present study reports the production of CA-loaded poly d,l-lactidecoglycolide acid (PLGA) devices by melt technique. HPLC-UV method was developed and validated to evaluate the uniformity and the release profile of the developed systems. The devices were also characterized by Fourier transform infrared spectroscopy, thermal analysis, and scanning electron morphology. It was studied the antiangiogenic activity of the CA-polymer system, using an in vivo model, the chorioallantoic membrane assay (CAM). CA was dispersed uniformly in the polymer matrix and no chemical interaction between the components of the formulation was verified. The implants presented a sustained release of the drug, which was confirmed by the morphological study and demonstrated an antiangiogenic activity. Therefore, the developed delivery system is a promising therapeutic tool for the treatment of ocular diseases associated with neovascularization or others related to the angiogenic process.

Resumo em Inglês:

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

Resumo em Inglês:

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

Resumo em Inglês:

The purpose of the study was to evaluate the antibacterial effect of protoporphyrin IX (PpIX) generated by the exogenous administration of 5-aminolevulinic acid or δ-ALA and activated with an argon laser over a planktonic and biofilm of Enterococcus faecalis (E. faecalis) as a pharmacological therapy alternative. A planktonic strain of E. faecalis was cultured with a solution of ∂-ALA (40 µg/mL)-thioglycolate solution for 13 min, and a biofilm of E. faecalis was cultured in a δ-ALA (80 µg/mL)-thioglycolate solution for 13 min. Then, both were irradiated with an argon laser. Finally, the antibacterial effect was evaluated by counting the CFU in planktonic form, and a LIVE/DEAD viability cell test. The production and accumulation of PpIX from exogenously administered δ-ALA on E. faecalis in planktonic and biofilm forms was confirmed by spectrofluorometry. The irradiation of PpIX with an argon laser produced an antibacterial effect on E. faecalis in planktonic and biofilm form, even without biofilm disruption, at a concentration of 40 µg/mL and 80 µg/mL of δ-ALA, respectively. The exogenous administration of δ-ALA in combination with laser irradiation on planktonic and biofilm forms of E. faecalis produces an effective antibacterial effect as complement or alternative to pharmacological therapies.

Resumo em Inglês:

T lymphocytes, cytokines, and macrophages play important roles in the clearance of Mycobacterium tuberculosis (Mtb) by the immune system. This study aimed to investigate the effects of isoniazid on the functions of both innate and adaptive immune cells. Healthy rats were randomly divided into experimental and control groups. Each group was randomly divided into three subgroups and named according to the duration of drug feeding, 1, 3, and 3 months followed by drug withdrawal for 1 month. The experimental groups were fed with isoniazid (12 mg/mL) and the control groups with normal saline. The percentage of CD4+ and CD8+T lymphocytes, level of interleukin (IL)-12 and interferon (IFN)-γ, and function of macrophages were determined at these three time points. Isoniazid significantly increased the percentage of CD4+T lymphocytes and the CD4+/CD8+T lymphocyte cell ratio (P < 0.05). It transiently (<1 month) enhanced the functions of rat macrophages significantly (P < 0.05). In summary, isoniazid could increase the percentage of CD4+T lymphocytes, CD4+/CD8+T lymphocyte cell ratio, and enhance macrophage function in healthy rats.

Resumo em Inglês:

Temozolomide, a chemotherapeutic drug that is often administered for the treatment of brain cancer has severe side effects and a poor aqueous solubility. In order to decrease the detrimental effect of the drug over healthy cells, a novel drug delivery vehicle was developed where the therapeutic drug was encapsulated within the hydrophobic cavities of b-CD modified magnetite nanoparticles, which are embedded in chitosan nanobeads prepared by salt addition. In-vitro studies have shown that the magnetic properties of the novel delivery vehicle are adequate for targeted drug delivery applications under an external magnetic field. Additionally, an increase in the amount of chitosan was shown to exhibit a strong shielding effect over the magnetic properties of the delivery vehicle, which lead to deterioration of the amount of captured drug at the targeted area, suggesting a delicate balance between the amounts of constituents composing the drug delivery vehicle.

Resumo em Inglês:

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco’s Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 μL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 μg/mL for the three different media.

Resumo em Inglês:

Vanadyl sulfate (VS) is an ingredient in some food supplements and experimental drugs. This study was designed to assay the effects of VS on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2. 30 male Wistar rats were divided into three equal groups as follow: non-diabetics, non-treated diabetics and VS-treated diabetics. Diabetes type 2 has been induced through high fat diet and fructose in the animals. Diabetic rats were treated with 25 mg/kgBW of VS in water for 12 weeks. At the end of study, glucose and insulin were measured using commercially available kits in serum and biomarkers of oxidative stress and inflammation in renal homogenates of animals were measured by related methods. Compared to controls, glucose and insulin were increased significantly in non-treated diabetic rats (p-value <0.05) that showed the induction of diabetes type 2 in rats. The results showed that in VS-treated diabetic rats compared to the non-treated diabetic group, vanadyl sulfate significantly reduced the glucose and insulin secretion and changed renal inflammatory and oxidative markers, except protein carbonyl so that we couldn’t find any significant changes. Our study showed that vanadyl supplementation had positive effects on oxidative stress and inflammation biomarkers in kidney of diabetic rats.

Resumo em Inglês:

The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Resumo em Inglês:

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury.

Resumo em Inglês:

The aim of the present study was to enhance the dissolution rate of an NSAID drug Ketoprofen by formulating it into solid dispersions with water soluble carrier Poloxamer 188 and Eudragit S 100. The solid dispersions of Ketoprofen with Poloxamer 188 were prepared at 1:1, 1:1.5 and 1:2 (Ketoprofen: Poloxamer 188) ratio by Solvent evaporation methods. The same concentration ratio was used for the preparation of solid dispersion with Eudragit S 100 by melting/fusion technique. Further, solid dispersions were investigated by solubility, ATR-FTIR, XRD, DSC, surface morphology, in-vitro dissolution and accelerated stability study. Results demonstrated that both Poloxamer 188 and Eudragit S 100 improve solubility of drugs by 8–10 folds. The result of ATR-FTIR study showed the slight shifting/broadening of principle peaks. In vitro dissolution studies showed that in the solid dispersion system containing Ketoprofen: Poloxamer 188 batch P2 (1:1.5) gives faster dissolution rate of Ketoprofen than the physical mixtures. The solid dispersion with Eudragit S 100, batch E1 (1:1) gives faster dissolution rate of Ketoprofen than the physical mixtures. In phase solubility study with Poloxamer 188 showed concentration dependent solubilization of drug but Eudragit S 100 produced opposite result. The effect of pH on solubility of Eudragit S 100 was carried out which showed solubility at pH 7.4. The dissolution profile of solid dispersion with Eudragit S 100 at pH 7.4 gives excellent result. The Accelerated stability of solid dispersions & its physical mixtures were studied at 400±2 °C/75 ± 5% RH for a period of 1 month. In these studies, Solid Dispersion batches produced an unstable formulation. The Ketoprofen solid dispersions with Poloxamer 188 and Eudragit S 100 could be introduced as a suitable form with improved solubility.

Resumo em Inglês:

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively.

Resumo em Inglês:

The effect of drying method, a process variable, on the powder and compaction properties of microcrystalline cellulose (MCC) obtained from the partial acid hydrolysis of bleached alpha (α) cellulose content of matured linters of Gossypium herbaceum (GH) was investigated. A portion of the wet MCC obtained was fluid bed dried at 60 ± 1 ºC, inlet air of 30 m3 min-1 for 3 h (coded MCC-GossF). The second portion was lyophilized at - 45 ± 2 ºC for 6 h (coded MCC-GossL). The physicochemical, scanning electron micrographs, X ray diffraction patterns and micromeritic properties of the derived MCCs were determined using standard methods. The cohesiveness and compactibility of the powders were investigated using Kawakita model while the deformation and compressibility pattern were determined using Heckel model. Avicel® PH 102 (AV-102) was used as comparing standard. Ash values of < 2%, pH (6.54 ± 0.23 to 6.58 ± 0.08), degree of polymerization, DP (231.50) was obtained. MCC-GossF had higher moisture content, swellability, better flow indices, and lesser porosity than MCC-GossL. Kawakita model demonstrated good consolidation and compactibility for both powders. Compacts of MCC-GossL were significantly (p < 0.05) harder than those of MCC-GossF. Heckel analysis demonstrated good compressibility and deformation pattern that was comparable with AV-102. Compacts of MCC-GossL had better mechanical and tablet compression properties than MCC-GossF. Method of drying significantly (p < 0.05) affected the powder and compaction properties of GH MCC.

Resumo em Inglês:

A simple, accurate, precise and robust stability indicating RP-HPLC assay method has been developed for the estimation of trimethobenzamide in stress sample. An isocratic separation of trimethobenzamide was achieved on Kromasil 100 C-18 column (250 X 4.6mm, 5µ) with a flow rate of 1.0 ml/min and by using a photodiode array detector to detect the analyte at 213nm. The optimized mobile phase consisted of methanol: ammonium formate (44:56, v/v). The drug was subjected to different forced degradation conditions according to ICH guidelines including acid, base, neutral hydrolysis, oxidation, photolysis and thermal degradation. Degradation products were found only in basic and oxidative degradation conditions. All the degradation products got eluted in an overall analytical run time of 12min. The developed analytical method has been validated according to the ICH guidelines. Response of trimethobenzamide was linear over the concentration range of 0.5-50µg/mL (r2 = 0.999). Accuracy was found to be in between 94.03% to 100.39%. Degradation products resulting from the stress studies did not interfere with the detection of the analyte.

Resumo em Inglês:

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11-21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.

Resumo em Inglês:

It is important to study the stability of plant extracts used as active ingredients in phytotherapic medicine, as degradation of the active principles directly affects the efficacy and safety of these products. Therefore, a stability study of the hydroalcoholic extract of the species: Mikania glomerata and Mikania laevigata was conducted in order to determine the speed of degradation and shelf life of these extracts, which are incorporated in cough syrup in Brazil. Leaves of both species were dried in an oven or by lyophilization (freeze-dried). Hydroalcoholic extracts underwent both accelerated stability study of six months and long-term stability study for 12 months. Samples were stored at different temperatures and every three months were analysed by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to monitor their chemical profile, quantifying coumarin and chlorogenic acid. For all conditions of the study, a reduction of the content of the chemical marker of this species, coumarin, greater than 5% was observed, so a shelf life of two years cannot be assigned to the hydroalcoholic extracts of these species as observed in commercial extracts.

Resumo em Inglês:

The aim of this work was to perform solubility studies for fexofenadine hydrochloride and establish dissolution conditions for this drug in oral suspension dosage form. The solubility study was executed through the shake-flask method, below 37 ºC±1 ºC, at 100 rpm stirring for 12 h in three buffer solutions: hydrochloric acid pH 2.0, acetate pH 4.5 and phosphate pH 6.8. The dissolution test was developed in vessels containing 900 mL of the same buffer, employing the paddle apparatus in speed of 25 and 50 rpm, below 37 ºC±0.5 ºC. The drug was classified as low solubility according to the Biopharmaceutics Classification System, since the dose/solubility ratio was higher than 250 mL in all media tested (326.55 mL in buffer pH 2.0; 2,456.33 mL in buffer pH 4.5 and 1,021.16 mL in buffer pH 6.8). The dissolution test showed that a release of 85% in 30 min could be established. The rotation speed of 25 rpm, media volume of 900 mL and insertion of the samples through weighted syringes are adequate. The buffered media pH 2.0 could be chosen as dissolution media.

Resumo em Inglês:

Oral fast-dispersible film was prepared by utlizing donepezil hydrochloride (drug) and various cellulose derivatives such as hydroxypropyl methyl cellulose (hypermellose) (HPMC), microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) to treat Alzheimer’s disease. NCC was synthesized by ultra-sonication method using MCC and this was converted to thinfilm formulation (NCC-F) using solvent casting technique. The interaction between the polymer and the drug was investigated by spectral analysis such as UV, FTIR, and 1H- NMR. FTIR confirmed that the compatibility of drug and polymer in ODF formulation. NCC-F has shown an average surface roughness of 77.04 nm from AFM and the average particle size of 300 nm from SEM analysis. Nano sized particle of NCC-F leads faster in vitro dissolution rate (94.53%) when compared with MCC-F and F3 formulation. Animal model (in vivo) studies of NCC-F formulation has reached peak plasma concentration (Cmax) up to 19.018 ng/mL in the span of (tmax) 4 h with greater relative bioavailability of 143.1%. These results suggested that high surface roughness with nanosized NCC-F formulation attained extended drug availability up to (t1/2) 70 h.

Resumo em Inglês:

Gold coated magnetite nanoparticles were prepared and coated with ranibizumab as an ocular drug delivery system. The surface morphologies of the nanoparticles were determined by Scanning Electron Microscopy (SEM). The size and surface charge were determined by using the dynamic light scattering (DLS) technique. Crystallographic properties of the gold coated Fe3O4 nanoparticles were recorded on X-ray diffractometer (XRD) the XRD pattern of nanoparticlees were shown to have uniqe Fe3O4 and gold peaks. Conjugation of ranibizumab onto nanoparticles was achieved using the physical adsorption method. The amount of ranibizumab on the surface of the nanoparticles was determined by thermogravimetric analysis (TGA). In the in vitro release studies performed using UV spectroscopy; it was found that almost 60% of antibodies were released within the first 30 minutes. Antibody activity after release studies was also proved with ELISA. Non-toxicity of gold coated Fe3O4 particles were proved with MTT. Results of the studies, showed that the antibody conjugated magnetic nanoparticle system could be a potential treatment system for ocular diseases.

Resumo em Inglês:

The membrane-based efflux pump systems are recognized to have an important role in pathogenicity and drug resistance in Mycobacterium tuberculosis by the extrusion of toxic substrates and drugs from the inner bacillus. This study aimed to investigate the in vitro interaction of Verapamil (VP), an efflux pump inhibitor, with the classical first-line anti-tuberculosis drug isoniazid (INH) in resistant and susceptible M. tuberculosis clinical isolates. Seven multidrug-resistant (MDR), three INH monoresistant and four susceptible M. tuberculosis clinical isolates were tested for the INH and VP combination by modified Resazurin Microtiter Assay Plate (REMA). Fractional Inhibitory Concentration (FIC) and Modulation Factor (MF) were determined. The INH plus VP combination showed no significant change in the Minimum inhibitory concentration (MIC) values of INH (FIC≥ 0.5; MF=1 or 2).The use of VP in tuberculosis therapy should be managed carefully, considering the resistance caused by specific mutation in katG and inhA genes, in which the use of these EPIs may have no success. The use of EPIs as an adjunctive drug in the anti-tuberculosis therapy should be further investigated on a larger number of M. tuberculosis clinical isolates with different resistant profile.

Resumo em Inglês:

Hospitalized patients with left ventricular failure (LVF) are at high risk for potential drug-drug interactions (pDDIs) and its related adverse effects owing to multiple risk factors such as old age, comorbidities and polypharmacy. This cross-sectional study conducted in two tertiary care hospitals aim to identify frequency, levels and predictors of pDDIs in LVF patients. Data about patients’ demographic, hospital stay, medication therapy, sign/symptoms and laboratory test results were collected for 385 patients with LVF. Micromedex Drug-Reax® was used to screen patients’ medication profiles for pDDIs. Overall prevalence and severity-wise prevalence of pDDIs were identified. Chi-square test was performed for comparative analysis of various variables. Logistic regression was applied to determine the odds-ratios (OR) for predictors of pDDIs. The prevalence of pDDIs was 96.4% (n=371). Overall 335 drug-interacting pairs were detected, which were presented in a total of 2870 pDDIs. Majority of pDDIs were of major- (48.9%) and moderate-severity (47.5%). Logistic regression analysis shows significant association of >6 all types of pDDIs with >12 drugs as compared with <8 drugs (OR=16.5; p=<0.001). Likewise, there was a significant association of >4 major-pDDIs with men as compared with female (OR=1.9; p=0.007) and >12 drugs as compared with <8 drugs (OR=10.9; p=<0.001). Hypotension (n=57), impaired renal function (23) and increased blood pressure (22) were the most frequent adverse outcomes associated with pDDIs. This study shows high prevalence of pDDIs in LVF patients. Majority of pDDIs were of major- and moderate-severity. Male patients and those prescribed greater number of medicines were more exposed to major-pDDIs.

Resumo em Inglês:

Hypericum sinaicum L. is an endangered Egyptian medicinal plant of high importance due to the presence of naphthodianthrones (hypericins), which have photodynamic properties and pharmaceutical potential. We sought to assess H. sinaicum ability to develop hairy roots that could be cultured in contained conditions in vitro and used as a source for hypericin production. We used four A. rhizogenes strains differing in their plasmids and chromosomal backgrounds to inoculate excised H. sinaicum root, stem and leaf explants to induce hairy root development. Additionally, inoculum was applied to shoots held in Rockwool cubes supporting their stand after removal of the root system. All explant types were susceptible to A. rhizogenes although stem explants responded more frequently (over 90%) than other explant types. The A4 and A4T A. rhizogenes strains were highly, and equally effective in hairy root induction on 66-72% of explants while the LBA1334 strain was the most effective in transformation of shoots. Sonication applied to explants during inoculation enhanced the frequency of hairy root development, the most effective was 60 s treatment doubling the percentage of explants with hairy roots. However, shoot transformation was the most effective approach as shoots developed hairy roots within 10 days after inoculation. Molecular analyses confirmed that the established hairy root cultures in vitro were indeed obtained due to a horizontal gene transfer from bacteria. These cultures grew fast and the hypericin content in hairy roots was about two fold higher than in H. sinaicum plants as determined by HPLC.

Resumo em Inglês:

This paper reports on the development of nanoparticles aiming at the in vitro controlled release of simvastatin (SVT). The nanoparticles were prepared by the nanoprecipitation method with polymers Eudragit® FS30D (EDGFS) or Eudragit® NE30D (EDGNE). EDGFS+SVT nanoparticles showed mean size of 148.8 nm and entrapment efficiency of 76.4%, whereas EDGNE+SVT nanoparticles showed mean size of 105.0 nm and entrapment efficiency of 103.2%. Infrared absorption spectra demonstrated that SVT incorporated into the polymer matrix, especially EDGNE. Similarly, the differential scanning calorimeter (DSC) curve presented no endothermic peak of fusion, indicating that the system is amorphous and the drug is not in the crystalline state. The maintenance of SVT in the amorphous state may favors its solubilization in the target release sites. In the in vitro dissolution assay, the SVT incorporated into the EDGFS+SVT nanoparticles showed a rapid initial release, which may be related to the pH of the dissolution medium used. Regarding the EDGNE+SVT nanoparticles, the in vitro release occurred in a bimodal behavior, i.e., an initial “burst” followed by a sustained delivery, with the kinetics of drug release following Baker-Lonsdale’s mathematical model. All these features suggest the nanoparticulate system’s potential to modulate SVT delivery and enhance its bioavailability.

Resumo em Inglês:

This study aims to investigate chemical composition of essential oils from Murraya paniculata (L.) Jack (Rutaceae) ripe and unripe fruits and determine their in vitro antibacterial activity. Essential oils were extracted by hydrodistillation from Murraya paniculata (L.) Jack ripe and unripe fruits collected in the Cerrado, in Rio Verde, southwestern Goiás, Brazil. They were analyzed by gas chromatography with flame ionization detector (GC-FID) and by gas chromatography-mass spectrometry (GC-MS). Sesquiterpenes, which represent the most abundant class of compounds in oils, predominated in both ripe and unripe fruits. Major constituents of essential oils extracted from ripe fruits (RF-EO) were (-caryophyllene (21.3%), (-ylangene (13.3%), germacrene-D (10.9%) and (-zingiberene (9.7%) whereas the ones of unripe fruits (UF-EO) were sesquithujene (25.0%), (-zingiberene (18.2%), germacrene-D (13.1%) and (-copaene (12.7%). In vitro antibacterial activity of essential oils was evaluated in terms of its minimum inhibitory concentration (MIC) values by the broth microdilution method in 96-well microplates. Both essential oils under investigation showed moderate anti-streptococcal activity against the following bacteria: Streptococcus mutans, S. mitis, S. sanguinis, S. sobrinus and S. salivarius. MIC values ranged between 100 and 400 µg/mL. Regarding the antimycobacterial activity, essential oils from M. paniculata (L.) Jack unripe and ripe fruits were active against Mycobacterium kansasii (MIC = 250 µg/mL), moderately active against M. tuberculosis (MIC = 500 µg/mL) and inactive against M. avium (MIC = 2000 µg/mL). This study was pioneer in revealing similar chemical profiles of both essential oils extracted from Murraya paniculata (L.) Jack unripe and ripe fruits, besides describing their in vitro anti-streptococcal and antimycobacterial activities.

Resumo em Inglês:

Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4.

Resumo em Inglês:

Solidago chilensis Meyen (= Solidago microglossa) popularly known as “Brazilian arnica” is used to treat of inflammatory disorders. S. chilensis is constant in the Therapeutic Memento of the Rio de Janeiro city and belongs to the medicinal species of Brazilian National List of Medicinal Plants of Interest of the Unified National Health System (SUS). There are no studies in the literature showing the direct activity of this plant species on immune system cells. The present study evaluated the chemical composition as well as the cytotoxic and pharmacological activity of the ether-ethanol extract from S. chilensis inflorescences (SCIE) in murine macrophage cell line J774A.1. The results showed that higher concentrations (50 to 200 µg/mL) of SCIE had significant cytotoxicity on J774A.1 cells, however, lower concentrations (from 10 to 0.1 µg/mL) did not produce significant cytotoxic effects and exhibited an inhibitory effect on nitric oxide production in LPS-stimulated J774A.1 cell line. The chemical analysis by HPLC-UV-PDA indicated that the SCIE contains flavonoid derived from quercetin and kaempferol; and diterpenes, probably labdanes. These findings complement data in the literature regarding the activity of this plant species on an important cell from the immune system involved in the innate and acquired immune response, the macrophages.

Resumo em Inglês:

Objectives. This study sought to compare the estimated glomerular filtration rate and the indication of dose adjustment of antimicrobials when using Cockcroft-Gault or Modification of Diet in Renal Disease. Methods. A cross-sectional study was performed with patients admitted to the intensive care unit of a Brazilian general hospital. The glomerular filtration rate was calculated for patients on all days using the Cockcroft-Gault and Modification of Diet in Renal Disease equations. The difference in estimated glomerular filtration and the dose adjustment indication of antimicrobials were assessed. Results. A total of 631 patients were included in this study. The median estimated glomerular filtration was significantly higher when estimated using Modification of Diet in Renal Disease (100.3 mL/ min/1.73 m2) than the estimation by Cockcroft-Gault (83.2 mL/min) [p<0.001]. Greater differences in estimations produced by the two formulae were observed in patients at extremes of weight and age, and a different dose adjustment was indicated for all antimicrobials assessed. Conclusions. These results demonstrate a significant difference in estimated glomerular filtration rate values when calculated using either Cockcroft-Gault or Modification of Diet in Renal Disease as well as in the indication of dose adjustment in an intensive care unit.

Resumo em Inglês:

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Resumo em Inglês:

In this study, we investigated the protective effects of Hedera nepalensis crude extract, its fractions and lupeol in alloxan-induced diabetic rats. Lupeol and n-hexane (HNN) fraction significantly reduced the blood glucose level by increasing insulin level in time dependent manner, and also significantly increased amylase and lipase activity in diabetic rats. Elevated levels of alanine transaminases (ALT), aspartate transaminases (AST), thiobarbituric acid reactive substances (TBARS), nitrite, hydrogen peroxide (H2O2), total bilirubin and total protein in blood serum were efficiently restored to normal levels. Suppressed enzymatic activity of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and peroxidase (POD) were also restored to their normal levels. Kidney functions were also restored to normal level after treatment with HNN and lupeol. HNN fraction and lupeol of H. nepalensis prevented oxidative stress in alloxan-induced diabetic rats. This study signifies the importance of H. nepalensis and lupeol in ameliorating diabetes by inducing insulin secretion in diabetic model rats.

Resumo em Inglês:

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers.

Resumo em Inglês:

Docetaxel-loaded acetic acid conjugated Cordyceps sinensis polysaccharide (DTX-AA-CSP) nanoparticles were prepared through dialysis and their release rates in vitro, particle sizes, zeta potentials, drug loading capacities, and encapsulation efficiencies were characterized for the synthesis of AA-modified CSPs from traditional Chinese medicine Cordyceps sinensis (Berk.) Sacc. Then, the AA-modified CSPs were characterized by 1H-NMR and FT-IR. Furthermore, the biocompatibility of the delivery carrier (AA-CSP nanoparticles) was assessed on human umbilical vein endothelial cells. In vitro antitumor activity studies on DTX-AA-CSP nanoparticles were conducted on the human liver (HepG2) and colon cancer cells (SW480). The DTX-AA-CSP nanoparticles were spherical and had an average size of 98.91±0.29 nm and zeta potential within the −19.75±1.13 mV. The encapsulation efficiency and loading capacity were 80.95%±0.43% and 8.09%±0.04%, respectively. In vitro, DTX from the DTX-AA-CSP nanoparticles exhibited a sustained release, and the anticancer activities of DTX-AA-CSP nanoparticles against SW480 and HepG2 were significantly higher than those of marketed docetaxel injection (Taxotere®) in nearly all the tested concentrations. The AA-CSP nanoparticles showed good biocompatibility. This study provided a promising biocompatible delivery system for carrying antitumor drugs for cancer therapy.

Resumo em Inglês:

Ethephon (Ethrel®) is an ethylene-based plant growth regulator that used in agriculture and it has direct and indirect effects on human health, direct effect via its inhalation during usage in agriculture and indirect effect through the diet (Fruits and vegetables) that is sprayed with it. The current study aimed to examine the possible modifying effects of costus (Saussurea lappa) root aqueous extract against Ethephon induced liver toxicity, injury, DNA fragmentation and PCNA alterations in male rats. Fifty adult male rats were divided into 5 groups (1st, control; 2nd, Costus; 3rd, Ethephon; 4th, Post treated Ethephon with costus; 5th, self-healing Ethephon). Current results revealed that; a significant increase in aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), liver injury, DNA damage and PCNA expressions in Ethephon group when compared with control group. In contrast; a significant decrease in albumin and total proteins in Ethephon group when compared with control group. Treatment of rats with costus after Ethephon improved these alterations as compared with Ethephon self-healing. So, it could be concluded that costus root extract worth to be considered as a natural substance for ameliorating the hepatic toxicity induced by plant growth regulator Ethephon.

Resumo em Inglês:

We performed this study to measure the Tumor Necrosis Factor-alpha (TNF-α) plasma level and to survey its correlation with disease activity in the newly diagnosed Rheumatoid Arthritis (RA) patients and those who were under treatment with the combination of Disease-Modifying Anti-Rheumatic Drug (DMARD) plus Prednisolone (PSL).We enrolled 30 newly diagnosed RA patients who received no treatment regarding their disease, 30 patients under treatment with the combination of Methotrexate (MTX) + Hydroxychloroquine (HCQ) + PSL and 30 healthy subjects in this case-control study from September 2017 to December 2017. The level of plasma TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) in each group. For assessment of disease severity, we used Disease Activity Score-28 (DAS-28) formula, and regarding DAS-28, we divided patients into four groups, including remission, low, moderate and high disease activity. There were no significant differences in the plasma level of TNF-α between the newly diagnosed RA patients and subjects who received MTX + HCQ + PSL, as well as healthy controls (p>0.05). There was a significant correlation between plasma levels of TNF-α and DAS-28 in the newly diagnosed patients with RA (r = 0.594, P = 0.001). Targeting TNF-α at the early stage of RA could have more beneficial effects on the amelioration of disease activity.

Resumo em Inglês:

Tacinga inamoena (K. Schum.) N.P. Taylor & Stuppy, also known as quipá, is a native cactus of the Caatinga used in traditional medicine to treat urethral infections and inflammation. This study aimed to determine the physicochemical characteristics of vegetal drug obtained from the roots of T. inamoena. Analytical techniques and phytochemical tests were used, such as thermal analysis, qualitative and semiquantitative determination of secondary metabolites and spectroscopy at the infrared region. The powder of the vegetal drug met the parameters established by the Brazilian Pharmacopoeia, except for compressibility, which was low. On the thermogravimetric curve, three events related to the mass loss were verified, which correlate with the vegetal drug quality control and play a part in their standardization. The qualitative screening suggested the presence of alkaloids, flavonoids and terpenes. The infrared spectrum reinforced the presence of hydroxyl, carbonyl, and ether groups. In the semiquantitative screening, a concentration for total polyphenols of 65 mg equivalent to gallic acid g-1 to the crude ethanol extract (CEE) was obtained. On the correlation of flavonoid content to seasonality, a concentration was obtained of 3.3 mg equivalent to quercetin g-1 to the CEE obtained during the drought period and of 10.6 mg equivalent to quercetin g-1 to the CCE obtained during the rainy season. In T. inamoena, the presence of important classes of secondary metabolites, which are associated with the pharmacognostic characterization, aids the authentication and quality control of vegetal drugs of importance in traditional Brazilian medicine.

Resumo em Inglês:

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.

Resumo em Inglês:

A new stability-indicating liquid chromatographic method was developed and validated for the estimation of glycopyrrolate in pharmaceutical formulations. A contemporary approach to analytical life-cycle management was followed to develop a robust and reliable chromatographic method. Scouted method variables such as % methanol, the strength of tetra butyl ammonium hydrogen sulfate and mobile phase flow rate were optimized using the design of experiment approach and their effect on critical quality attributes was studied. The critical quality attributes viz. retention time, theoretical plate count and symmetry factor were highly influenced by the three critical method variables. Optimum chromatography was attained on a C-18 column with a mobile phase methanol: 10 mM tetra butyl ammonium hydrogen sulfate (80:20, v/v) flowing at 1.0 mL.min-1. Chromatographic method specificity was ensured by degrading the drug forcefully. Validation studies postulated method acceptability and suitability for estimating glycopyrrolate in both bulk as well as injection formulation. Results for parameters viz. linearity (5-250 µg.mL-1), accuracy (>99%) and precision (<2%) advocated method reliability. Overall the method was reliable and of optimum quality and, possess the potential of application in routine and bio-analytical purposes.

Resumo em Inglês:

In this study, naftifine (a topical antifungal drug) loaded poly(vinyl) alcohol (PVA)/sodium alginate (SA) nanofibrous mats were prepared using the single-needle electrospinning technique. The produced nanofibers were crosslinked with glutaraldehyde (GTA) vapor. The morphology and diameter of the electrospun nanofibers were studied by scanning electron microscopy (SEM). SEM images showed the smoothness of the nanofibers and indicated that the fiber diameter increased with crosslinking and drug loading. Atomic force microscopy (AFM) images confirmed the uniform production of the scaffolds, and elemental mapping via energy dispersive X-ray spectroscopy (EDS) showed the uniform distribution of the drug within the nanofibers. An attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy study demonstrated that naftifine has sufficient secondary interactions with the polymer blend. The crosslinking treatment decreased the burst drug release effectively and the release mechanism followed Korsmeyer-Peppas Super Case-II transport. Overall, these findings suggest the potential use of naftifine-loaded PVA/SA nanofibers as a topical antifungal drug delivery system.

Resumo em Inglês:

Donkey’s milk represents a good alternative to human milk because of its chemical characteristics similar to those of human’s. In present study, the pro- and anti-inflammatory effects of donkey’s milk were evaluated on peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 12 young and 12 aged normal subjects. PBMCs were cultured with or without the optimal and non-cytotoxic dose of pasteurized donkey’s milk, and polymyxin B was used to inhibit the possible endotoxin contamination. Following 18 hours incubation, culture supernatants were harvested to measure the secreted Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-8 (IL-8) and Interleukin-10 (IL-10) by ELISA. Donkey’s milk significantly increased TNF-α (p= 0.01), IL-8 (p< 0.0001), IL-6 (p< 0.0001) and IL-10 (p= 0.01) levels in PBMCs. In addition, the levels of IL-6 (p= 0.002), IL-8 (p= 0.002) and TNF-α (p= 0.002) from aged subjects were significantly higher compared with young subjects. In contrast with these data, the level of IL-10 was markedly reduced from aged subjects (p= 0.02). Considering the immune-potentiation effects of donkey’s milk, it is suggested investigating milk as a beneficial dietary component for up-regulating the immune response in aged people.

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The aim of this study was evaluate the in vitro antifungal activity of crude extracts from Eugenia uniflora, Libidibia ferrea and Psidium guajava. The extracts were obtained by turbo-extraction using water (AQ) or acetone-water (AC-W) (7:3, v/v) as solvents and lyophilized to obtain the crude extracts (CE). The CE were characterized by UV-Vis, TLC and HPLC. The activity of CEs was investigated against clinical isolates of Candida spp. and the Minimum Inhibitory Concentration (MIC), MIC50 and MIC90 were determinated. The analysis by TLC showed that all CEs presented polyphenols (flavonoids and tannins). The CEs from E. uniflora showed higher amount of polyphenols (30.35 ± 2.15%, AC-W) and the HPLC analysis revealed the tannins in all extracts. The CEs of E. uniflora showed MIC range from 1.9 to 500.0 µg/mL, and lower values of MIC50 and MIC90 against non-albicans Candida isolates. Regarding L. ferrea and P. guajava, the results showing MIC from 3.9 to 1000.0 µg/mL (CE-AQ) against C. albicans. The results demonstrate antifungal performance from CE against various species of Candida spp., suggesting that the herbal species may be use as new potential antifungal agents. Additionally, the polyphenol content can play a pivotal role in the antifungal properties of CE.

Resumo em Inglês:

The processing of grapes for the manufacture of juices and wines, generates large quantities of by-products rich in metabolites with antioxidant, antimicrobial, anti-inflammatory and cicatrizing activities. The high homology between human enzymes and snake venoms makes the latter valuable laboratory tools for the study of pathophysiological processes. Proteases and phospholipases A2 act in processes related to hemostasis and inflammatory response. Thus, in this work, dried pomace obtained from grape (Isabel, Niagara, Bordô, BRS Violeta and Blend cultivars) processing were evaluated on phospholipase, proteolytic, hemolytic and thrombolytic activities induced by snakes venoms and the content of phenolic compounds and minerals was evaluated. The dried pomace exerted inhibitory and potentiating actions in all analyzed activities. The enzymatic modulators present in the evaluated dried pomace have potential for therapeutic use, although their broad characterization is still necessary, in order to define adequate amounts and formulations to obtain efficacy and safety in their use.

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Up to date, the management of hepatotoxicity induced by a suicidal or unintentional overdose of acetaminophen (APAP) remains a therapeutic challenge. The present study aimed to elucidate the potential effect of sitagliptin, a DPP-4 inhibitor, to ameliorate the acute injurious effects of acetaminophen on the liver. APAP toxicity was induced in mice by an intraperitoneal injection of APAP (400 mg/kg). The effect of treatment with sitagliptin, initiated 5 days prior to APAP injection, was evaluated. Serum indices of hepatotoxicity, oxidative stress markers in liver tissues, serum IL-1β, and TNF-α in addition to hepatic- NF-E2-related factor-2 (Nrf2) were determined. Our results showed that APAP induced marked hepatic injury as evidenced by an increase in serum levels of ALT and AST, in addition to the deterioration of histological grading. Oxidative stress markers, serum TNF-α, and IL-1β were also elevated. Sitagliptin successfully ameliorated the histological changes induced by APAP, improving liver function tests and liver oxidant status accompanied with a marked increase in Nrf2 level in hepatic tissues. Thus, the hepatoprotective effects of sitagliptin in this animal model seem to involve Nrf2 modulation, coincidental with its anti-inflammatory and antioxidant effects.

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The in-vitro antioxidant activity of Rhaponticum acaule essential oil (RaEO) was evaluated using β-carotene/linoleic acid bleaching, chelating activity, and lipid peroxidation inhibition (TBARS) assays. The antimicrobial activity of RaEO was assessed by disc diffusion and microdilution methods against 8 bacteria and 4 yeast. Finally, the allelopathic activity of RaEO on the seed germination and the shoot and root elongation of lettuce (Lactuca sativa L.) seedlings were investigated. According to our results, the RaEO exhibited significant antioxidant activity, similar to those of standards (BHT and ascorbic acid) with IC50 values of 0.042 and 0.045 mg/mL obtained by β-carotene bleaching and TBARS assays, respectively. On the other hand, despite its interesting ferrous chelating activity, RaEO possesses moderate IC50 value (0.35 mg/mL) as compared with that of EDTA (0.015 mg/mL). RaEO exhibited a strong antimicrobial activity against all the tested microorganisms, with IZ, MIC and MBC values being in the range of 7.67 ± 0.58 to 13.33 ± 0.58 mm, 1.25 to 5.00 and 5.00 to 10.00 mg/mL, respectively. The results reveled also that RaEO inhibited the shoot and root growth of Lactuca sativa L. seedlings. Our data suggested that the RaEO had pharmaceutical benefits and could be used as a potential natural herbicide resource.

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Microbial translocation is associated with the increased risk of cardiovascular disease in HIV-infected individuals. There is scarce information regarding the possible associations between the biomarkers of microbial translocation, inflammation and cardiovascular risk that can be evaluated in clinical laboratories using plasma or serum samples. This systematic review was conducted according to the PRISMA protocol in order to verify the most used soluble biomarkers of microbial translocation, inflammation and cardiovascular risk, as well as possible associations between them, in HIV-infected individuals. A search was performed using the Medline, Scopus and Web of Science databases to identify existing studies regarding the relationship between microbial translocation biomarkers, inflammation and cardiovascular risk in HIV-infected patients. Eleven articles that presented soluble biomarkers of microbial translocation (LPS, rDNA, sCD14, LBP and EndoCAb) were selected. The most frequently evaluated soluble biomarker was sCD14, followed by LPS; the latter were associated with some lipid profile parameters. This systematic review considered soluble blood biomarkers that can be utilized in laboratory diagnosis. The aim was to identify the interconnection between microbial translocation, inflammation and cardiovascular risk. Despite the fact that a large number of inflammation and cardiovascular risk biomarkers have been previously reported, it was noted that important markers involved in the pathophysiology of cardiovascular diseases need to be included in future research.

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To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

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This study aimed to analyze the antiarthritic activity of ginkgolic acid against the Complete Freund’s Adjuvant (CFA)-induced arthritis in rats. Arthritis was induced through an intradermal injection of CFA (0.1 mL) at the right hind footpad of adult Wistar Albino rats. Ginkgolic acid was administered orally at doses of 25 mg/kg and 50 mg/kg, respectively, once daily via gavage for 25 days upon inducing arthritis. Indomethacin was administered orally at a dose of 3 mg/kg twice in a week which served as positive control group. The animals were sacrificed and subjected to biochemical and histopathological analysis upon completion of treatment. Ginkgolic acid was able to reverse the arthritic effect (p < 0.01) induced by CFA in a dose dependent manner. Swelling of paw, thymus and spleen index, serum biomarker levels, and pro-inflammatory cytokines were significantly reduced (p < 0.01) by the acid whereas the antioxidant enzyme activities were remarkably restored. The histopathological findings were in agreement with the biochemical results. The results indicate that the antioxidant and anti-inflammatory properties of ginkgolic acid can be credited to the antiarthritic effects, and it can be promoted as a potential agent for therapeutic use against osteoarthritis.

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The therapeutic approaches for Type 2 Diabetes Mellitus rely most on the usage of oral hypoglycaemic drugs. These drugs have adverse side effects and hence alternative medicines are continuously explored. The present study intends to investigate the antidiabetic potential of the flavonoids present in Gracilaria corticata. The flavonoids were isolated (FEGC) and their inhibitory activity on the carbohydrate hydrolysing enzymes such as α-amylase and α-glucosidase was analysed. The flavonoids were found to inhibit α-amylase and α-glucosidase with an IC50 value of 302 µg and 75 µg respectively. The synergistic effect of FEGC and luteolin was also investigated and the results show that both FEGC and luteolin inhibited synergistically at half their IC50 values. The observations of this study reveal that the flavonoids of G. corticata have potential antidiabetic activity and can act independently or synergistically in the management of Type 2 Diabetes Mellitus

Resumo em Inglês:

Cnidoscolus chayamansa is a native plant of the Mayan region, which is also cultivated in other places like northern Mexico, Tunisia and India. Many properties are attributed to Mayan Chaya, such as aid in the control of glycemia in diabetics. Thus this study aimed to evaluate the hypoglycemic effects of chaya aqueous extracts in a model of streptozotisin-induced diabetic Wistar rats. Chaya aqueous extracts were collected from plants cultivated in Quinta Roo (Mayan region) and Durango (northern Mexico), and in this study we compare their effect with metformin (as a control). Additionally, we compared the extracts mass profiles from both regions by high-resolution liquid chromatography coupled to a triple quadrupole tandem mass detector (HPLC-MS/MS QQQ). Finally, a study of the pancreatic tissue was carried out to evaluate the effects of the extracts on the Langerhans islets. Both extracts showed a good hypoglycemic effect after two weeks of treatment, and the Langerhans islets showed a partial recovery due to the effect of the treatment. Although the plants were cultivated at a distance of 2,350 km and under different weather, the compounds found in both did not show significant differences.

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Pharmaceutical care (PC) is in the implementation process in Brazil and Latin America. Synthesis of evidence has been requested for monitoring and evaluating the process regarding the treatment effect. The objective is to build and disseminate a systematic review protocol to make a standard for updating results from pharmaceutical care for hypertension and for other diseases. This is a protocol for systematic review studies regarding a real example of a protocol reasoned in pharmaceutical care for hypertension in primary care. This protocol was delineated grounded in the Cochrane Handbook. Descriptors and words were defined using MeSH (Medical Subject Headings), DeCS (Descriptors in Health Sciences) and Emtree thesaurus, and the search was performed in English, Spanish and Portuguese, without filters, up to March, 27th, 2017. The results were structured in the PRISMA flowchart. Results found from all databases were: the Cochrane Library (n= 202); PubMed (n= 2608); LILACs (n= 909); Embase (n= 1653); Scopus (n=1298); IPA (n=967); and Web of Sciences (n=435). From these, 1688 were duplicate articles. The content of this paper can aid the constant monitoring of pharmaceutical care implementation and contribute to the improvement of the quality and evidence levels of published studies.

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This study aimed to determine the effects of a vitamin D deficiency on aortic functional and structural properties in diabetic rats. Diabetic rats were induced with 50 mg/kg streptozotocin and divided into two equal groups: diabetic rats on a normal diet (DR) and diabetic rats on a vitamin D-deficient diet (DRD). Non-diabetic rats that received a normal diet were the controls (CR). At the end of 10 weeks, rats were sacrificed and aortic rings with and without the endothelium were studied in tissue organ baths for isometric force measurements. Histology of aortic tissue was performed to determine the intima-media thickness. Serum levels of 25-hydroxyvitamin D in the DRD group were significantly decreased compared to the CR and DR groups. Acetylcholine-induced endothelium-mediated relaxation was significantly impaired in DR and DRD compared to CR. Endothelium-dependent contraction to calcium ionophore was significantly augmented in DR and DRD aortas compared to CR. The responses to acetylcholine and calcium ionophore were similar in DRD and DR. There were no significant differences in relaxation to sodium nitroprusside or contraction to phenylephrine between aortas of the groups. The intima-media thickness was significantly greater in the DR group compared to the CR group, and this structural change was augmented in aortas of the DRD group. In conclusion, this study showed that endothelial function was impaired with diabetes, and a vitamin D deficiency did not aggravate endothelial dysfunction. However, diabetes with a vitamin D deficiency demonstrated smooth muscle hypertrophy and an increased aortic media thickness.

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Origanum vulgare L. (OVEO) essential oil has been considered a candidate antimicrobial for use in food conservation systems. However, studies on the influence of concomitant variations of different food components or physicochemical parameters on the antibacterial properties of OVEO are scarce. This study assessed the influence of concomitant variations in amounts of proteins - PTN (4.0, 6.0 or 8.0 g/100 mL) and lipids - LIP (3.75, 5.0 or 6.25 g/100 mL) and pH values (5.0, 5.5 or 6.0) in cultivation medium on the inhibitory effects of OVEO against Escherichia coli (EC) and Salmonella Typhimurium (ST). Lowest minimum inhibitory concentration values of OVEO against EC and ST were observed in media with the highest LIP amounts regardless the PTN amount and pH value. In absorbance based microtiter plate assay (MPA), for both EC and ST, OVEO caused the lowest Grmax values in medium containing the highest LIP and PTN amounts and lowest pH value. Highest Grmax values for EC and ST were observed in medium containing the lowest LIP and PTN amount and highest pH value. Grmax values estimated from viable counts of EC and ST in tested media with OVEO confirmed bacterial growth behavior similar to that observed in MPA. Overall, the LIP amount in media was as the most influential factor to enhance the antibacterial effects of OVEO. These results indicate that the concomitant influence of LIP and PTN amounts and pH values on the antibacterial effects of OVEO should be considered for optimizing its antimicrobial efficacy in foods.

Resumo em Inglês:

Due to the increase of bacterial resistance, the search for new antibiotics is necessary and the medicinal plants represent its most important source. The aim of this study was to evaluate the antibacterial property of extract and fractions from Protium spruceanum leaves, against pathogenic bacteria. By means of diffusion and microdilution assays, the crude extract was active against the nine bacteria tested being the hydromethanolic fraction the most active. During phytochemical procedures, procyanidin (1) and catechin (2) were identified as the main antibacterial constituents of this fraction. In silico results obtained using PASSonline tool indicated 1 and 2 as having good potential to interact with different targets of currently used antibiotics. These results no indicated potential to none DNA effect and indicated the cell wall as mainly target. Electrophoresis result supported that had no DNA damage. Cell wall damage was confirmed by propidium iodide test that showed increased membrane permeability and by cell surface deformations observed in scanning electronic microscopy. The in vitro assays together with the in silico prediction results establish the potential of P. spruceanum as source of antibacterial compounds that acts on important bacterial targets. These results contribute to the development of natural substances against pathogenic bacteria and to discovery of new antibiotics.

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Considering the importance of an adequate composition of the formulation in the development of stable, safe and effective cosmetic products, experimental design techniques are tools that can optimize the formulation development process. The objective of this study was to develop topical formulations using the Box-Behnken design with response surface methodology and evaluate its physical, sensory and moisturizing properties. The experimental design used in the first step allowed to identify and to quantify the influence of raw materials, as well as the interaction between them. In the second step, the analysis identified the influence of soy lecithin, the phytantriol and capric acid triglyceride and caprylic on the consistency index, stickiness and greasiness and skin hydration. Cetearyl alcohol, dicetyl phosphate and cetyl phosphate 10EO and acrylates/C10-30 alkylacrylate crosspolymer showed effects in rheological parameters. The addition of soy lecithin had significant effects in terms of consistency index, stickiness, oiliness and immediate moisturizing effects. Phytantriol showed effects on increasing consistency index and oiliness sensation. Thus, the experimental design was shown to be an effective tool for research and development of cosmetics, since it allowed the assessment of the individual and interaction effects of raw materials in the responses: rheological parameters, sensory and clinical efficacy.

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The objective of this work was to develop and characterize liposomes loaded with silver nanoparticles (LAgNPs) to show improvement in stability characteristics. AgNPs were prepared by the green synthesis method with Aloe vera gel extract and exposure to sunlight. Liposomes were prepared by the modified reverse phase method. Particle size, polydispersity index, zeta potential, as well as the scanning electron microscopy (SEM) morphological aspects of AgNPs and LAgNPs were evaluated. In addition, was used flame atomic absorption spectroscopy to determine the amount of AgNP that was encapsulated in liposomes. The AgNPs presented as amorphous and polydisperse structures, with a mean diameter of 278.46 nm and zeta potential of -18.3 mV. LAgNPs had a mean diameter between 321 and 373 nm, the polydispersity index close to 0.2 and a zeta potential around -40 mV, which indicates greater stability to the AgNPs. The images obtained by SEM show semicircular structures for AgNPs and well-defined spherical shape for LAgNPs. The percentage of encapsulation was between 51.81 to 58.83%. These results showed that LAgNPs were obtained with adequate physicochemical characteristics as a release system.

Resumo em Inglês:

Few topical products have been developed specifically to treat acute and chronic arthritis and inflammation, using non-steroidal anti-inflammatory drugs (NSAIDs). The lack of dosing accuracy commonly found in locally applied semisolid products for cutaneous use is a critical issue that leads to treatment failure. The aim of the present work is to develop a differentiated and innovative topical patch based on a monolithic hydrogel for ibuprofen skin delivery, in order to provide a safer and accurate way of drug administration along with improved treatment compliance. Topical patches based on hydroxypropylmethylcellulose (HPMC) were optimized in composition, in terms of enhancer and adhesive, supported on a systematic assessment of in vitro release and permeation behavior and adhesion properties. Several mathematical models were used to scrutinize the release mechanisms from the patches. In vitro release kinetics was shown to be mainly driven by diffusion. However, other mechanisms seemed to be also present, supporting the feasibility of using patches for sustained drug delivery. PEG 200 provided the best permeation rate, with a permeation enhancement ratio of ca. 3 times higher, than the commercial reference. The addition of Eudragit L30D 55 to the formulation led to the best adhesion profile, thus achieving a successful development based on a safe-by-design concept.

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Abstract The present study describes a method for simultaneous analysis of cocaine, benzoylecgonine and cocaethylene in urine samples. After solid phase extraction, Gas Chromatography-Mass Spectrometry was used for identification and quantification. The calibration curves were linear at 20 - 3000 ng/mL, r2 0.9997 for benzoylecgonine, 15 - 2000 ng/mL, r2 0.9985 and r2 0.9993 for cocaine and cocaethylene, respectively. Accuracy values: cocaine: 93,5 - 102,1%; benzoylecgonine: 97,5 - 104,8%; cocaethylene: 90,6 - 101,5%. Precision values: cocaine: C.V 5,4 - 14,6%; benzoylecgonine: C.V 7,8 - 12,3%; cocaethylene: C.V 5,9 - 12,3%. Detection and quantification limit values: cocaine and cocaethylene:10 ng/mL and 15 ng/mL, respectivalty; benzoylecgonine:15 ng/mL and 20 ng/mL, respectivaley. Recovery values: cocaine: 78,0 - 85,8%; benzoylecgonine: 74,0 - 79,8%; cocaethylene: 83,0 - 91,5%. The method described is advantageous compared to others, as it simultaneously detects the major analytes found in urine samples due to cocaine use and has been successfully validated.

Resumo em Inglês:

Lomefloxacin is a flouroquinolone antibiotic that is quite efficacious against many gram negative and gram positive pathogens. Lomefloxacin evince antibacterial effects by modifying DNA gyrase in gram negative pathogens and topoisomerase IV in gram positive pathogens. This study is designed to assess the immunomodulatory effects of lomefloxacin in male albino mice. Three doses of lomefloxacin 12.5 mg/kg, 25 mg/kg and 50 mg/kg were used and delayed type hypersensitivity assay, cyclophosphamide induced neutropenic assay, carbon clearance assay, heamagglutination assay and mice lethality test were performed to evaluate the effects of lomefloxacin on immune system of mice. DTH assay has depicted the significant immunosuppressant potential of lomefloxacin at 25 mg/kg and 50 mg/kg dose. Total leukocyte count have exhibited highly significant reduction (P<0.001) in leukocyte count after cyclophosphamide administration. Differential leukocyte count has shown significant (P<0.01) reduction in lymphocyte count, whereas, highly significant (P<0.001) increase in monocyte count and significant (P<0.05) increase neutrophil count has been observed. In carbon clearance assay, highly significant (P<0.01) increase in phagocytic index has been noted at 12.5 mg/kg and 25 mg/kg doses. Humoral immune system responses are suppressed in dose dependent manner by both heamagglutination assay (P<0.001) and mice lethality assay (P<0.001). Results clearly depict that lomefloxacin possess quite significant immunomodulatory potential.

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In Brazil, thalidomide is manufactured by a public laboratory, distributed by the Unified Health System (SUS), and regulated by the National Health Surveillance Agency (Anvisa). Despite the concerns regarding the adverse effects of thalidomide, few drug utilization studies have been conducted to describe processes and outcomes related to this drug. The aim of this study was to elucidate the issues related to the utilization and control of thalidomide, and patient safety within the scope of SUS. In this cross-sectional study, we evaluated the articulation between an outpatient dermatology service of a referral hospital in infectology, the manufacturer, and Anvisa. Four data sources were used: i) interviews with health professionals; ii) data from the Customer Service of the manufacturer, iii) data on adverse events reported to Anvisa, and iv) adverse events identified in outpatient service. Most health professionals interviewed knew the major thalidomide-related adverse effects. None of them ever reported adverse events to Anvisa or contacted the Customer Service. For over three years, there were 330 calls concerning thalidomide at Customer Service, 7% of which were related to adverse events. During a period of six years, Anvisa was notified of only 15 adverse events. Health professionals were aware of the adverse events associated with thalidomide, but not the necessity to report them. The low number of notifications recorded by Anvisa and the information obtained from Customer Service show that pharmacovigilance remains incipient. A pharmacovigilance system that integrates all the services associated with thalidomide is required to strengthen this activity within the SUS to improve patient safety.

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The use of medicines can be an indicator of healthcare access. Our aim was to evaluate the consumption of medicine and associated factors among adults in Manaus Metropolitan Region, located in the north of Brazil. A cross-sectional population-based study was conducted with adults, ≥18 years old, selected by probabilistic sampling. The outcome was the use of medicine in the previous 15 days. Poisson regression with robust variance was used to calculate the prevalence ratio (PR) of medicine consumption, with 95% confidence interval (CI). Use of medicines was reported by 29% (95% CI: 28-31%) of the participants. People with good (PR: 0.82, 95% CI: 0.72-0.94) and fair (PR: 0.77, 95% CI: 0.65-0.90) health status were shown to use less medication than those with very good health. People with partners (PR: 1.19, 95% CI: 1.08-1.31), and people who had sought healthcare service in the fortnight (PR: 2.16, 95% CI: 1.97-2.37) showed higher medicine consumption. Medical prescription (80.1%) was the main inductor of consumption; purchasing at a drug store (46.4%), and acquiring through the Brazilian Unified Health System (39.6%) were the main ways to obtain medicines. About one-third of adults in the Metropolitan Region of Manaus used medicines regularly, mainly people with very good health, living with partners, and with recent use of a health service.

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Antibacterial activity and good mechanical properties are some of the characteristics required for an appropriate film dressing. A novel polymer blend was developed for wound healing application. Twenty-four formulations using the polymers chitosan, poly(vinyl alcohol) and/or ɛ-Polylysine and the plasticizer glycerol were designed using factorial design and then the films were prepared by the casting/solvent evaporation method. Seventeen films were obtained among the twenty-four proposed formulations that were characterized by Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared Spectroscopy (FTIR). Mechanical properties, such as tensile strength (σ), elongation at break (ɛ) and Young’s modulus (Y) as well as antibacterial properties were determined. The best candidate was then further analyzed with regard to porosity, Water Vapor Transmission Rate (WVTR), swelling and cytotoxicity experiments. The results showed a film with semi-occlusive characteristics, good mechanical properties and no toxic. Incorporation of ɛ-Polylysine increased antibacterial activity against gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria.

Resumo em Inglês:

Rutin is a flavonoid glycoside, mainly consists of phenolic compounds, responsible for many biological activities. The objective of the present study was to develop and validate a precise, simple, robust, rapid and reliable reverse phase high -performance liquid chromatography (RP-HPLC) technique by using Qbd approach for evaluating the rutin in nanoparticles. Central composite design (CCD) was employed for optimizing the experimental conditions of RP-HPLC method. Buffer pH, methanol content in the mobile phase composition, flow rate, and wavelength were selected as independent variables whereas retention time, peak area, and asymmetry factor was selected as dependent variables. The retention time, peak area and asymmetric factor of rutin by using optimized independent variables were found to be 3.75 min, 1014.79 mV, and 1.26 respectively. The limit of detection and limit of quantitation values were found to be 0.005 µg/mL and 0.15 µg/mL respectively. For confirming linearity, accuracy, precision, and robustness, the optimized assay condition was validated as per ICH guidelines. The proposed method, which was optimized by QbD approach was found to be a suitable method for analyzing the rutin in chitosan-sodium alginate nanoparticles.

Resumo em Inglês:

Ethnomedicinal survey documents the traditional practices of Tetrastigma angustifolia leaves in the management of diabetes in the North-eastern region of India. The present study was aimed at isolation of possible antidiabetic principle(s) from T. angustifolia leaves and evaluation of antidiabetic efficacy of isolated compound(s) in experimental animal model. The methanolic extract of T. angustifolia leaves was obtained by Soxhlet extraction method and subjected to silica gel column chromatography (100-200 mesh). Fraction 18-176 chloroform:methanol (70:30) yielded a pale yellow colored compound. The structure of pure compound was elucidated with the help of UV, IR, NMR and Mass spectrometric/techniques. The antioxidant activity of the isolated compound was evaluated in vitro by various radical scavenfing assay methods.. Oral acute toxicity study was carried out according to OECD guideline 423 in Wistar rats. The antidiabetic efficacy of the isolated compound was evaluated in STZ-induced diabetic rats at the dose of 5 mg/kg b.w. for duration of 21 days. The present study reports a new flavocnoid compound isolated from the methanolic extract of T. angustifolia leaves and identified as 8-hydroxyapigenin 7-O-D-glucopyranoside. The flavonoid compound exhibited potent antidiabetic (hypoglicemic) activity in STZ-induced diabetic rats with promising antioxidant (radical scavenging activity) potential in vitro.

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The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Resumo em Inglês:

Diabetes is an independent risk factor for the development of cardiovascular disease, with approximately 80% of cardiovascular mortality and morbidity linked to vascular complications such as atherosclerosis. It has been estimated that up to one-third of patients with diabetes mellitus use some form of complementary and/or alternative medicine. One plant that has received attention from diabetic patients for its perceived antidiabetic properties is Clinacanthus nutans, a member of the Acanthaceae family that is known as snake grass. Ethnomedical applications of this herb have been identified for the treatment of certain conditions, including fever, diabetes, skin rashes, and insect bites. This review aims to assess the potential of C. nutans to be used in the prevention and/or treatment of diabetic vasculopathy. Evidence for antidiabetic, anti-inflammatory, and dyslipidemic properties of C. nutans, as shown from experimental studies, is presented and discussed. Diabetes, inflammation, and hyperlipidemia are known to play significant roles in the initiation and severity of diabetic cardiovascular disease; thus, targeting these factors might be beneficial for preventing and/or treating diabetic vasculopathy.

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With the widespread use of high-efficiency antiretroviral therapy (HAART), the life expectancy of HIV-infected patients has been significantly extended. However, the metabolic complications among HIV-infected patients treated with HAART have become the most common problem in the world. It is very important to explore the incidence of dyslipidaemia and studies on the role of potential risk factors in HIV-infected Chinese patients treated with HAART are sparse. Therefore, we designed current study, to investigate the effects of therapeutic intervention and continuous information support on the lifestyle of HIV/AIDS patients with dyslipidaemia. Three hundred and six HIV/AIDS patients admitted to the AIDS clinic in Beijing from January 2016 to January 2017 were recruited and assigned into two groups: the treatment group (n=64) and the control group (n=64). The median age of the participants was 38.8±11.0 years (range 20-75 years). The prevalence of dyslipidemia in control and treatment group was (59/64) 92.2% and (53/64) 82.8%, respectively. In this study, low HDL-cholesterol (HDLC) led to abnormalities 47/64 (73.3%) in the control group and 35/64 (54.7%) in HAART-treatment group. Additionally, HAART group showed higher triglyceride, total cholesterol, and low-density lipoprotein (246.1±171.8, 1.73±1.61 mmol/L, 4.46±1.1 mmol/L, 2.54±0.74 mmol/L). In multivariate analysis, gender, marital status, high BMI, dietary habits and physical activity were potential risk factors for dyslipidemia in HIV-infected Chinese patients. In this study, we reported high prevalence dyslipidemiain two HIV infected groups. We suggest that the appropriate diagnosis should be performed for analyzing the metabolic complications in HIV-infected Chinese patients. Further studies are very important to understand the role of potential risk factors in metabolic complications.

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Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund’s complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats.

Resumo em Inglês:

Adverse changes occur gradually in the skeletal muscles with age via continuous exposure to oxidative stress. Quercetin, a member of the flavonoids family, possesses anti-oxidative and radical-scavenging activities. Therefore, this study investigated the role of quercetin to modulate age-induced changes in the transcript levels of some apoptosis-related genes in rat’s gastrocnemius muscles, up to 15 months-old. Half of the rats at each age (1, 5, 10 and 15 months old) were given a vehicle and the other half was given 200 mg/kg quercetin for 2 weeks, respectively. With the increase of age, vehicle groups showed hyalinization of the muscle fibers and a decrease of the catalase and an increase of the malondialdehyde levels. Down-regulation of Bcl2 gene and up-regulation of both NF-κB and Bax genes were recorded. Interestingly, quercetin groups showed focal hyalinization of the muscle fibers at both 10th and 15th months old. An increase in the catalase and a decrease in malondialdehyde levels, up-regulation of Bcl2 gene and down-regulation of both NF-κB and Bax genes were recorded. In conclusion, quercetin minimized age-induced alteration in the morphological structure and the expression of the apoptosis-related genes via increasing the antioxidant defense in the gastrocnemius muscle.

Resumo em Inglês:

Metabolic syndrome (MS) is a serious health problem worldwide; it is characterized by a group of metabolic disorders, including central obesity, insulin resistance/type 2 diabetes, hyperlipidemia with accelerated atherosclerosis, hypertension, non-alcoholic fatty liver disease, and elevated uric acid with increased risk of gout. The incidence of MS has increased considerably in recent decades and has attracted considerable attention. A number of clinical and translational laboratory studies have implicated the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in the development of MS, therefore establishing a strong link between chronic inflammation and metabolic diseases. This paper aims to review new developments on NLRP3 inflammasome in MS for better understanding of chronic inflammation in metabolic diseases. We will also provide new insights into using NLRP3 inflammasome as an innovative therapeutic target.

Resumo em Inglês:

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Resumo em Inglês:

A repetitive batch process was employed followed by membrane ultrafiltration system to produce low-cost cyclodextrins (CDs) using commercial enzymes Toruzyme® cyclomaltodextrin glucanotransferase (CGTase) and its kinetic parameters were determined. The ultrafiltration system enabled the removalof inhibitory products from the reaction medium, allowing the enzyme to be recovered for reuse. A 10 kDa membrane was used to separate the different CDs produced by the CGTase. The substrates evaluated were maltodextrin, corn starch and cassava starch at 5, 10 and 15% (w/V), in the presence and absence of 10% (V/V) ethanol. After reaction for 132 h, 10% (w/V) cassava starch in the presence of ethanol provided the best results with 32.1 mg/mL of β-CD. Maximum production occurred after 72 h of reaction, with a yield of 87.4% of β-CD and an α-CD, β-CD and γ-CD production ratio of 1:1:0.08 g, respectively. When eight repetitive batches of 72 h followed by ultrafiltration and crystallization of β-CD were performed, 2.1 g of precipitate was obtained with a purity of 67.6% β-CD. The supernatant from the crystallization process was lyophilized and resulted in 35.3% α-CD. The developed model can be used industrially for the production of low cost CDs from easily obtained raw material.

Resumo em Inglês:

Paclitaxel spirulina nanoparticles were said to have promising anticancer activity against gastric cancer. Nanoparticles of paclitaxel-spirulina were prepared for treating gastric cancer using precipitation technique. The synergistic anticancer efficiency againstMKN45 cells retains when the paclitaxel and spirulina were encapsulated into nanoparticles. To increase the site specific delivery, intra-tumoral administration was carried in the in vivo evaluation. There was an increase in overall survival in an MKN45-transplanted mice model and notable improvement in anti-tumour efficacy when paclitaxel-spirulina nanoparticles were delivered through intra-tumoral administration. The further investigation of overall anticancer mechanism of these nanoparticles is made as a major part in this research. Hence, the conjecture of this research is that, the paclitaxel-spirulina encapsulated nanoparticles could be an effective chemotherapeutic formulation for gastric cancer.

Resumo em Inglês:

Urea’s thermal instability and burning on sensitive skin can cause problems for cosmetic formulations. To overcome these drawbacks, urea was incorporated into ordered mesoporous silica (SBA-15). SBA-15 was synthesized using tetraethyl orthosilicate and Pluronic® P123 in an acid medium. Urea (20 wt.%) was incorporated into calcined SBA-15 by the incipient wetness impregnation method. Several techniques were used to characterize the samples. Skin hydration and transepidermal water loss were measured using Corneometer® CM 825 PC and Tewameter® 300 TM. Results showed that the structural properties of SBA-15Urea were similar to pure SBA-15, indicating that SBA-15 remained structured even after urea incorporation. Nitrogen physisorption data showed the volume and surface area of the pores in SBA-15Urea were much lower than those in SBA-15, demonstrating that urea was deposited inside the mesopores. In vivo moisturization studies revealed that SBA-15Urea was not able to reduce transepidermal water loss compared to the other products and control, while forming a non-occlusive surface film on the skin. We conclude that incorporation of urea in the pores of the inorganic SBA-15 matrix is a promising approach to enhancing its stability and providing a prolonged moisturizing effect.

Resumo em Inglês:

Ursodeoxycholic acid (UDCA), a secondary bile acid (BA), has been used as a drug to treat various liver diseases. UDCA is synthesised from cholic or chenodeoxycholic acid (CA/CDCA), two primary BAs frequently used as the starting materials. Nowadays, swine, cattle, and poultry bile are the main sources of those BAs. However, other commercial animals could be promising sources as well. We identified two livestock, two poultries, and eight fishes that are commercially cultivated in Indonesia. Four free BAs including CA, CDCA, deoxycholic acid (DCA), and lithocholic acid (LA) were identified for their occurrences using thin-layer chromatography and high-performance liquid chromatography. CA was detected in cow, duck, red tilapia, gourami, the common carp, and grouper, whereas CDCA was only detected in two poultries and the common carp. The occurrence of DCA was common and abundant in most tested animals. In contrast, the presence of LA was found to be very low in all samples. The biliary bile of tilapia has been found to contain a high abundance of free CA (43% of the total bile). A simple extraction was able to purify CA from biliary bile of tilapia. This is a new promising and competitive source of CA.

Resumo em Inglês:

Studies that addressed the profile of pharmaceutical activities and behaviors in community pharmacies in the last decades pointed to a gap between community pharmacy practice and the precepts of the profession. Facing the need to analyze whether the new legislation has impacted this scenario, the objective of this study was to describe the general profile and academic profile of community pharmacists, and the profile of the activities they develop, as well as to know their place of work. This is a descriptive study, to which all pharmacists in charge of community pharmacies in the metropolitan area of ​​Belo Horizonte-MG (n = 1624) were invited. Data collection was performed through a questionnaire validated online, from October to December 2017, via Google Docs®. Responses were obtained from 109 pharmacists, most of them female, aged 31-40 years, being general graduates, and in private institutions. Pharmacotherapeutic follow-up, an activity linked to clinical management, is performed by only 37.60% of pharmacists, evidencing that there is still a lag in relation to the provision of clinical services by community pharmacists. Thus, we emphasize the importance of implementing the precepts established by Brazilian curricular guidelines for undergraduate pharmacy courses which focus on the development of clinical skills, since the insertion of the pharmacist into the health team and the provision of clinical services to the community can add new value to the use of medications, and contribute effectively to their rational use in Brazil.

Resumo em Inglês:

Lignosus rhinocerotis (tiger milk mushroom) is widely used by the indigenous people of Malaysia as a traditional remedy. The present study was carried out in order to evaluate the antioxidant, cytotoxic and anti-neuroinflammatory activities of L. rhinocerotis extract on brain microglial cells (BV2). The antioxidant activity was evaluated by 2,2-diphenyl-1-picryhydrazyl (DPPH•), 2,2’-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS•+) scavenging assays, and ferric reducing antioxidant power (FRAP). The FRAP, DPPH and ABTS•+ scavenging capacities of the TE3 fraction were 420.77 mg FE/g, 58.01%, and 7%, respectively. The cytotoxic activity was determined by MTS assay. The in vitro model of anti-neuroinflammatory property was evaluated by measuring the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced BV2 cells. The TE3 fraction showed a significant NO reduction at 1 to 100 µg/mL. The TE3 fraction down-regulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) genes while it upregulated heme oxygenase (HO-1) and NADPH quinone acceptor oxidoreductase-1 (NQO-1) genes. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription was also activated. The chemical component of the active fraction (TE3) was identified by gas chromatography-mass spectrometry (GCMS). Overall, the BV2 in vitro model anti-neuroinflammatory activity of L. rhinocerotis may be caused by the lipid constituents identified in the fraction.

Resumo em Inglês:

The aim of present work was to investigate blends of Eudragit® NE 30D with Aquacoat® ECD using different ratios to eliminate curing effect associated with individual polymers. Propranolol HCl 10% w/w was layered onto sugar cores using 5% w/w HPMC as a binder. Drug-layered-cores were coated either with pure or blends of Aquacoat® ECD: Eudragit® NE 30D in a fluidized bed coater to obtain 20% w/w coating level. Talc 35% w/w was used as anti-tacking agent. The pellets were characterized for in vitro dissolution studies, morphology, water uptake-weight loss, osmolality and adhesion of coating after curing at 60 °C or 60 °C/75% RH for 24 h. The findings revealed that Aquacoat® ECD coated pellets showed curing effect due to further gradual coalescence of polymeric particles which resulted into better film formation upon curing. In contrast, the curing effect of Eudragit® NE 30D coated pellets was caused by decrease in adhesion of coatings after curing which provided entirely different swelling behavior of uncured (localized swelling) and cured (uniform swelling) pellets. The undesired curing effect of individual polymers was eliminated by using their blends in appropriate ratio.

Resumo em Inglês:

This study was aimed to calculate in detail the costs of a medication dispensing service in community pharmacy in Brazil. Descriptive and retrospective analysis with a cost analysis based on mixed costing; absorption costing and time-driven activity based-costing, considering year 2018 and both public and private health system perspectives within a one-year time horizon to estimates costs related to implement and to deploy the service, costs per patient and costs per activity of process (US$ 1 = R$ 3.8310 in October, 2018). Total costs of dispensing service ranged from US$ 24,451.61 to US$ 37,914.48. Costs per patient ranged from US$ 2.43 to US$ 3.77. Costs per activity of the process ranged from US$ 0.39 in pharmacotherapy assessment to US$ 2.46 in pharmaceutical interview. This provides evidence to deploy and implement a structured medication dispensing service in community pharmacy in Brazil with a view to optimize the usage of medicines.

Resumo em Inglês:

Conventional drug formulations are incapable of adequate delivery of proteins and peptides for therapeutic purposes. As these molecules have very short biological half-life, multiple dosing is required to achieve the desirable therapeutic effects. Microspheres are able to encapsulate proteins and peptide in the polymeric matrix while protecting them from enzymatic degradation. In this study Bovine Serum Albumin (BSA) matrix type microspheres were fabricated using Polylactide-co-glycolide (PLGA) by double emulsion solvent evaporation method. The effects of variables such as homogenizer speed, molecular weight of polymer and the effect of pH of the water phases, were investigated against factors such as drug loading, encapsulation efficiency, morphology, size, drug distribution and release profile of the microspheres. Results, suggested that an increase in homogenization speed leads to a decrease in microsphere size. The increase in homogenization speed also caused a significant effect on the release profile only when higher molecular weight of polymer had been used.. The pH change of the internal aqueous phase led to modification of surface morphology of spheres to a porous structure that significantly increased the total amount of released protein. Integrity of protein structure was intact as shown by SDS-PAGE. According to the results, it can be concluded that we achieved a reproducible method regarding controlled protein delivery for different sizes of particles.

Resumo em Inglês:

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer’s disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.

Resumo em Inglês:

The objective of the study was to evaluate different types of cancer and its chemotherapy in various ethnic groups of Pakistan. Ethnic groups includes, Pukhtoons, Punjabis, Sindhis, Muhajirs, Siraikis, Memoons, Hazaras, Hindkos, Baltis, Gilgitis, Kashmiris, and Afghanis. The data was collected from well reputed hospitals located in the different provinces of Pakistan. The collected data was taken from 15 hospitals where around 8500 patients visited during 2010 to 2017. From the visited patients, 8356 were analyzed for their ethnicity, age and sex while, 144 patients (male 77 and female 67) were excluded from analysis due to incomplete information or loss of follow-up. Among 8356 patients, 3762 were male (45%) whereas, 4594 were female (55%). The chemotherapy was carried out as per National Comprehensive Cancer Network guidelines (NCCN- guidelines). The most common five prevalent cancer among these ethnic groups were Head and Neck, Blood, Respiratory, Genito-urinary and Breast cancer. The most common cancer in female was breast cancer while, head and neck cancer was more prevalent in male. It can be concluded that the prevalence of cancer in Pakistan is very alarming, which may be due to lack of awareness, illiteracy, lack of national cancer control programs, and economics issues.

Resumo em Inglês:

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Resumo em Inglês:

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Resumo em Inglês:

Diabetes was investigated as a risk factor for nephrotoxicity induced by vancomycin. In the present study, the drug’s nephrotoxic effect was indirectly evaluated by Glomerular Filtration Rate, albuminuria and serum levels of creatinine and urea on the 1st, 7th and 14th days of vancomicyn therapy in a group of diabetic and non-diabetic patients, with and without previous nephropathy. The correlations between investigated variables (including the population’s epidemiological profile and hospital care) were measured by the Spearman test. The sample consisted of 132 patients, predominantly male diabetic patients with previous nephropathy, over 40 years, receiving ≥ 10 grams of vancomycin for the treatment of infectious diseases and showing satisfactory clinical outcomes. A risk of vancomycin drug interaction with potential nephrotoxic outcome was observed in 36.4% of patients who used multiple drugs. Furthermore, 80% of patients had an increase of at least 0.5 mg.dL-1 in baseline serum levels of creatinine and urea at the end of the study. This was more common among the diabetic patients with previous nephropathy, showing higher albuminuria and a reduction in the Glomerular Filtration Rate. Therefore, it has been recommended that the use of vancomycin in diabetic patients should be in careful dosages and that kidney functioning be monitored.

Resumo em Inglês:

The Gαq-RGS2 loop activator, 1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)-phenyl)-1H-1,2,4-triazol-5(4H)-one has demonstrated Gαq signaling inhibitor activity. Therefore, we aimed to study the effect of Gαq-RGS2 loop activator on isolated heart and aorta of normal rats. Heart and aorta were isolated from the sacrificed rats (n=6) and mounted on the langendroff’s and organ bath assembly, respectively. The effect of various receptor-dependent (acetylcholine, angiotensin II and adrenaline) and independent (calcium chloride and sodium nitroprusside) agonists in absence and presence of Gαq-RGS2 loop activator on left ventricular systolic pressure (LVSP) and the contractile responseswere evaluated in isolated heart and aorta, respectively. Gαq-RGS2 loop activator (100 µM) significantly attenuated the adrenaline (p<0.001,) and angiotensin II (p<0.001) induced increase in LVSP in isolated heart and contractile response of adrenaline (p<0.01) and angiotensin II (p<0.01) in the aorta. However, effect calcium chloride did not significantly alter by Gαq-RGS2 loop activator. The effect of acetylcholinewas significantly (p<0.01, p<0.05) increased by Gαq-RGS2 loop activator in isolated heart and aorta. The effect of sodium nitroprusside significantly (p<0.01) potentiated by Gαq-RGS2 loop activator (100 µM) in isolated heart while it did not significantly alters in the aorta. Ultimately, the Gαq-RGS2 loop activator modulated the action of receptor-dependent agonists in isolated heart and aorta.

Resumo em Inglês:

p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.

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Intralesional corticosteroid injection (ICSI) is known as one of the main methods used for treating a wide range of lesions. It also results in a high concentration of drugs at lesion sites, with minimal systemic absorption. Thus, this study aimed to provide a review of the intralesional corticosteroid injection (ICSI) indications in the treatment of oral lesions. To this end; relevant key words were searched in the databases of PubMed, Google Scholar, Scopus, ScienceDirect, and UpToDate in the present study. Accordingly, the results of a total number of 62 case reports or case series articles were used in this study and the positive therapeutic effects of intralesional corticosteroid injection (ICSI) in 23 common oral lesions were reported. The most common type of intralesional steroid in the treatment of oral lesions was triamcinolone. No significant difference was also observed in terms of pain in patients following the use of steroid alone or in combination with anesthetic agents; moreover, the reported side effects of this method were exceptionally rare and transient. It was concluded that the intralesional corticosteroid injection (ICSI) could be one of the effective therapeutic methods with no significant problems in many oral lesions such as inflammatory, immunologic, and vascular ones due to its higher therapeutic effects than other topical forms of steroids and fewer side effects than systemic corticosteroid.

Resumo em Inglês:

Alzheimer disease (AD) is characterized by a low level of acetylcholine, beta-amyloid (Aβ) aggregation and oxidative stress. Donepezil is the core medicine used for the treatment of AD. Various structural modifications of donepezil have been carried out. Benzylpiperidine part of donepezil has been replaced with benzylpyridine, pyridyl methylpiperidine, benzylpiperazine, pyrimidyl piperazine. These derived molecules showed promising activities as anti-Alzheimer agents. Replacement of indanone part by other heterocyclic rings such as pyridine resulted in the formation of compounds which exhibited monoamine oxidase (MAO) as well as acetylcholinesterase (AChE) inhibition. Propargylamine containing derivatives displayed AChE as well as MAO inhibition properties. Attachment of donepezil with natural compounds like ferulic acid, flavonoids, and curcumin showed antioxidant activities in addition to inhibition of the AChE. Benzylpiperidine and benzylpiperazine have also been combined with condensed heterocyclic rings and these compounds displayed promising anti-Alzheimer properties. This review highlights the important structural modifications of donepezil and their influence on biological activities as anti-Alzheimer agents.

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At the hospital, the pharmacist is constantly challenged to prepare extemporaneous solutions from tablets, capsules or drug powder for patients unable to swallow, such as pediatric, elderly and patients that use nasoenteric and nasogastric tubes. The preparation of extemporaneous solutions from capsules, tablets and drug powder requires stability studies analysis. This article is a bibliographic review of preparation of extemporaneous oral liquid from solid oral dosage forms used in clinical practice. The selected articles contain all the information regarding manipulation techniques, pharmaceutical excipients, packaging, storage conditions and results of stability studies above 90% performed by HPLC analysis. In addition, a situational analysis of the strategies for the preparation of the extemporaneous solution was described to help the manipulator in the decision. The preparation of extemporaneous solution from solid oral dosage forms is based on information from official compendium or scientific literature, to ensure safe and effective manipulated medicine.