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Brazilian Journal of Pharmaceutical Sciences, Volume: 58, Publicado: 2022
  • Study of anti-diabetic, beta-carotene-bleaching inhibiting and iron chelating properties of Carissa opaca root extracts Article

    Ahmed, Dildar; Malik, Wajeeha; Maqsood, Maria; Atique, Iqra; Qamar, Muhammad Tariq

    Resumo em Inglês:

    Abstract Degenerative diseases diabetes and oxidative stress constitute a major health concern worldwide. Medicinal plants are expected to provide effective and affordable remedies. The present research explored antidiabetic and antioxidant potential of extracts of Carissa opaca roots. Methanolic extract (ME) was prepared through maceration. Its fractions were obtained, sequentially, in hexane, chloroform, ethyl acetate and n-butanol. An aqueous decoction (AD) of the finely ground roots was obtained by boiling in distilled water. The leftover biomass with methanol was boiled in water to obtain biomass aqueous decoction (BAD). The extracts and fractions showed considerable porcine pancreatic α-amylase inhibitory activity with IC50 in the range of 5.38-7.12 mg/mL while acarbose had 0.31 mg/mL. The iron chelating activity in terms of EC50 was 0.2939, 0.3429, 0.1876, and 0.1099 mg/mL for AD, BAD, ME, and EDTA, respectively. The EC50 of beta-carotene bleaching activity for AD, BAD, ME, and standard BHA were 4.10, 4.71, 3.48, and 2.79 mg/mL, respectively. The total phenolic content (TPC) and total flavonoid content (TFC) of AD and BAD were also considerable. In general, ethyl acetate fraction proved to be the most potent. Thus, the C. opaca roots had excellent antioxidant activity while having moderate α-amylase inhibitory potential.
  • Development and evaluation of topical formulations that contain hydroethanolic extract from Schinus terebinthifolia against HSV-1 infection Article

    Nocchi, Samara Requena; Ferreira, Lilian dos Anjos Oliveira; Castro-Hoshino, Lidiane Vizioli de; Truiti, Maria da Conceição Torrado; Natali, Maria Raquel Marçal; Mello, João Carlos Palazzo de; Baesso, Mauro Luciano; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; Ueda-Nakamura, Tânia

    Resumo em Inglês:

    Abstract The therapeutic drugs to treat Herpes simplex virus (HSV) infections have toxic side effects and there has been an emergence of drug-resistant strains. Therefore, the search for new treatments for HSV infections is mounting. In the present study, semi-solid formulations containing a crude hydroethanolic extract (CHE) from Schinus terebinthifolia were developed. Skin irritation, cutaneous permeation, and in vivo therapeutic efficacy of the formulations were investigated. Treatment with the ointment formulations did not result in any signs of skin irritation while the emulsions increased the thickness of the epidermis in Swiss mice. The cutaneous permeation test indicated that the CHE incorporated in the formulations permeated through the skin layers and was present in the epidermis and dermis even 3 h after topical application. In vivo antiviral activity in BALB/c mice treated with the CHE ointments was better than those treated with the CHE emulsions and did not significantly differ from an acyclovir-treated group. Taken together, this suggests that the incorporation of CHE in the ointment may be a potential candidate for the alternative topical treatment of herpetic lesions.
  • Perceptions of Pharmacy students about their competences for professional practice in community pharmacy Article

    Coelho, Marina Melo Antunes; Mesquita, Alessandra Rezende; Lima, Marina Guimarães

    Resumo em Inglês:

    Abstract Pharmaceutical education should enable the development of competences for community pharmacy practice, which is an important field for the pharmacist workforce. The aim of this study was to evaluate the competences perceived by pharmacy interns from a Brazilian pharmacy school for community pharmacy practice. This study adopted a combined quantitative and qualitative approach. The study cohort included undergraduate students who undertook internships in community pharmacy in the final year of the pharmacy course. Students responded to an 11-item structured questionnaire according to a five-point Likert scale that included perceptions of their competences for community pharmacy practice. Among the 693 possible answers, 605 (87.3%) agreed that the course promoted the development of competences for professional practice in community pharmacy. Less than 70% of students perceived themselves as prepared to respond to symptoms and provide non-prescription medicines. Qualitative analysis of the comments revealed three themes: the need to improve patient information skills, improve practice as a member of a health care team, and improve dispensing according to legal requirements. These findings may support improvements in undergraduate pharmacy programs, such as the inclusion of experiential learning, active learning methods, interprofessional education, and development of clinical skills.
  • Effect of rape flower on benign prostatic hyperplasia in rats Article

    Han, Song-Chan; Yun, Young-Hak

    Resumo em Inglês:

    Abstract We were carried out to investigate the efficacy of Rape (Rapeseed, Brassica napus L.) flower on BPH (benign prostatic hyperplasia) in rats. We found that the extract from Rape flower prevented hyperplasia in testosterone-induced BPH model, the relevant animal model of human BPH. Extract reduced the weight of prostate and induced significantly cell apoptosis in prostate in BPH model. In addition, the extract controlled expression of TGF-β1 in prostate gland and promoted urinary output in dose-dependence in BPH model. Our data provide that Rape flower may be useful for treatment of BPH.
  • Association of reproductive risk factors and comorbidities among molecular subtypes of Breast cancer in a Tertiary care Hospital Article

    Sankar, Veintramuthu; Rama, Parthasarathy; Mohammed, Shareena; John, Subash; Sivakumar, Veluswamy; Rodrigues, Prudence A

    Resumo em Inglês:

    Abstract The reasons for the recently observed increase in the incidence of breast cancer in the Indian population are not clearly understood, but thought to be largely explained by westernization of lifestyles and changes in reproductive behavior, which characterize exposure to hormones. Our aim is to review the reproductive risk factors and comorbidities and evaluate the association between molecular subtypes of breast cancer. A hospital-based analytical case-control study was conducted among the breast cancer cases with controls in a multispecialty teaching hospital for a period of one year. Totally, 130 subjects were recruited and an interview was conducted using a structured questionnaire to obtain demographic and risk factor data, including tissue marker status (ER, PR and HER-2) obtained from case files. Data were analyzed with SPSS-20 version. Results: The highest age group reported in this study was 51- 60 years which has a 3.8 times increased risk compared to other age and the age group of 31- 40 have a decrease risk of 0.33. In this study, the percentage of post menopause (68%) and mothers not breastfeeding (10%) was higher in cases compared to controls and a noted increase in the risk of breast cancer with odds ratio (OR) of 2.745 (p= <0.0001) and 9.08 (p=0.01) respectively. Duration of breastfeeding showed significantly (p=<0.0001)) moderate positive correlation (r=0.549, 0.457, 0.418 and 0.636) for luminal A, luminal B, HER+, and triple negative respectively. This study found that all the reproductive risk factors do not have correlation with a molecular subtype of breast cancer except breastfeeding. Post menopause and breastfeeding were common factors associated with all people and could be modifiable to prevent the occurrence of breast cancer through lifestyle changes.
  • Blood glucose related adverse drug reaction of antitumor monoclonal antibodies: a retrospective analysis using Vigibase Article

    Yang, Jincheng; Zhao, Bin; Zhou, Haiyan; Jia, Bei; Chen, Lianzhen

    Resumo em Inglês:

    Abstract On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.
  • Anti-hyperlipidemic and anti-diabetic evaluation of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy Article

    Azam, Khadija; Rasheed, Muhammad Adil; Omer, Muhammad Ovais; Altaf, Imran; Akhlaq, Amina

    Resumo em Inglês:

    Abstract The use of plants in disease treatment is cost effective and relatively safe. This study was designed to investigate anti-hyperlipidemic and anti-diabetic activity of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy in hyperlipidemic & diabetic mice. Eight groups comprising five mice each were used. Group A was hyperlipidemic control, group B, C, D received atorvastatin (20 mg/kg), leaf extract (200 mg/kg) and leaf extract in combination with atorvastatin (200 mg/kg and 20 mg/kg) orally for 15 days. Group E was diabetic control. Group F, G, H received sitagliptin (40 mg/kg), leaf extract (200 mg/kg) and extract in combination with sitagliptin (200 mg/kg and 40 mg/kg) orally for 7 days. Blood cholesterol levels were measured at 1st, 5th, 10th and 15th day and fasting blood sugar levels were measured at 2, 12, 24, 72 and 168 hours during treatment. One-way ANOVA with tukey- kramer multiple comparison test was used. The chemical characterization of ethanolic extract of Catharanthus roseus leaves showed presence of alkaloids, saponins, tannins and flavonoids. Ethanolic extract of Catharanthus roseus has significant anti-hyperlipidemic & anti-diabetic effects (p<0.05, p<0.01) when compared with control but had not cause significantly increase in anti-hyperlipidemic effects of atorvastatin. While significantly increased the antidiabetic effect of sitagliptin (p<0.05).
  • Pain management & opioid dose reduction with topical sevoflurane instillations in intractable venous ulcers: a case report Article

    Fernández-Ginés, F. Dámaso; Cortiñas-Saenz, Manuel; Agudo-Ponce, Desirée; Morales-Molina, José Antonio; Sánchez, Carmen Fernández; Sierra-Garcia, Francisco

    Resumo em Inglês:

    Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.
  • Pharmaceutical services in primary health care: dissatisfaction among users, managers and pharmacists Article

    Cruz, Manuela Martins; Heringer, Karla Oliveira dos Santos Cassaro; Lyrio, Cristiane; Brasil, Girlandia Alexandre; Lima, Ewelyne Miranda de; Endringer, Denise Coutinho; Lenz, Dominik; Rezende, Ana Maria Bartels; Andrade, Tadeu Uggere de

    Resumo em Inglês:

    Abstract To assess the performance indicators for pharmaceutical services (PS) in primary health care (PHC), the level of satisfaction with pharmacy services among users and managers / pharmacists’ impressions in relation to the findings were evaluated. The study used mixed methods, including a retrospective and descriptive study of the performance indicators for PS in PHC, an observational study on the level of satisfaction and a qualitative study of users’ perception of pharmacy services at Health Units. Managers and pharmacists’ impressions of the study results were also collected. Only 44.4% of pharmacies had a full-time pharmacist. From the establishments visited, 5.3% did not have an air-conditioned environment, and only 33.3% of the items essential to the Good Practices of Storage of Medicines and Supplies criteria were fulfilled. Although 77.9% of the prescribed medicines were dispensed, it did not reach the 80% standard. The satisfaction level of users was 3.2±0.6, indicating dissatisfaction with pharmacies’ services. By means of an evaluation of each item within the questionnaire, it was possible to observe that variables related to pharmaceutical care presented low scores in relation to other domains, thus evidencing the fragility of the pharmaceutical- patient relationship in users’ perception. Managers and pharmacists suggested that these results were related to the inadequate physical infrastructure of pharmacies, work overload, lack of recognition and undervaluation of pharmacists, lack of interaction within the PHC team, high turnover of pharmacists, and lack of PS prioritization by the administration. PS in PHC has structural and organizational weaknesses that require changes. In general, users are dissatisfied with pharmacies’ services, especially with pharmaceutical care.
  • Neuroprotective role of Tinospora cordifolia extract in streptozotocin induced neuropathic pain Article

    Archana, Jorige; Annapurna, Akula; Devayani, Panuganti

    Resumo em Inglês:

    Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.
  • Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization Article

    Agrawal, Gopal Prasad; Maheshwari, Rajesh Kumar; Mishra, Pradeep

    Resumo em Inglês:

    Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.
  • Antinociception Induced by Moringa Stenopetela (Baker f.) Cufod. Leaves Extract and Possible Mechanisms of Action Article

    Hussein, Muna Cemal; Bektas, Nurcan; Ozturk, Yusuf; Arslan, Rana

    Resumo em Inglês:

    Abstract Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.
  • The impact of therapeutic hypothermia on peripheral blood cell in newborns with hypoxic ischemic encephalopathy Article

    Kurt, Abdullah; Zenciroğlu, Ayşegül; Akduman, Hasan

    Resumo em Inglês:

    Abstract The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.
  • Formulation development and pharmacokinetic studies of long acting in situ depot injection of risperidone Article

    Dubey, Vineet; Saini, Tulsi Ram

    Resumo em Inglês:

    Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.
  • Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties Article

    Zong, Shuai; Liu, Yuting; Park, Hyun Jin; Ye, Ming; Li, Jinglei

    Resumo em Inglês:

    Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.
  • Bioactivities of Alchemilla mollis, Alchemilla persica and Their Active Constituents Article

    Kurtul, Ekin; Eryilmaz, Müjde; Sarialtin, Sezen Yilmaz; Teki̇n, Mehmet; Acikara, Özlem Bahadir; Çoban, Tülay

    Resumo em Inglês:

    Abstract The aim of this study was to determine antimicrobial activities of Alchemilla mollis, Alchemilla persica as well as ellagic acid and miquelianin against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans by using microbroth dilution method and anti-inflammatory activity by using human red blood cell (HRBC) membrane stabilization method. Microbroth dilution method was used to determine the antimicrobial activities. Extracts possessed activity having MIC values of 2.5-5-10mg/ mL, compounds possessed activity having MIC values of 1.25-2.5-4-5mg/mL. A.mollis aerial parts displayed the highest anti-inflammatory activity (IC50=1.22±0.07mg/mL). Ellagic acid and miquelianin were also determined as anti-inflammatory agents with 0.57±0.01mg/mL and 1.23±0.02mg/mL IC50 values, respectively. Total phenolic content and tannin content of the A.mollis and A.persica were determined as 357.00±75.80mg, 282.50±28.70mg PGE/g plant material and 18.02%, 18.63% respectively according to the method described by European Pharmacopoeia. Ellagic acid, miquelianin and catechin were analyzed by HPLC. The highest catechin content was detected in A.persica roots (6.69±0.05g/100g plant material). A.mollis aerial parts contain higher miquelianin (0.39±0.02g/plant material) and ellagic acid (1.56±0.01g/ plant material) than A.persica.
  • Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice Article

    Liu, Xiaohua; Xue, Zhiyuan; Wang, Bo; Wang, Ying; Zhang, Mengting; Feng, Shilan

    Resumo em Inglês:

    Abstract Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-β-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-β-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali.
  • In vitro anti-inflammatory, anti-arthritic and anti- proliferative activity of green synthesized silver nanoparticles - Phoenix dactylifera (Rothan dates) Article

    Khader, Syed Zameer Ahmed; Ahmed, Sidhra Syed Zameer; Mahboob, Mohamed Rafi; Prabaharan, Selva Barathi; Lakshmanan, Shanmugasundaram Olapalayam; Kumar, Kishore Ramesh; David, Daniel

    Resumo em Inglês:

    Abstract Traditionally dates is consumed as a rich source of iron supplement and the current research discuss the synthesis of silver nanoparticles (AgNPs) using methanolic seed extract of Rothan date and its application over in vitro anti-arthritic, anti-inflammatory and antiproliferative activity against lung cancer cell line (A549). FTIR result of synthesised AgNPs reveals the presence of functional group OH as capping agent. XRD pattern confirms the crystalline nature of the AgNPs with peaks at 38º, 44º, 64º and 81º, indexed by (111), (200), (220) and (222) in the 2θ range of 10-90, indicating the face centered cubic (fcc) structure of metallic Ag. HR- TEM results confirm the morphology of AgNPs as almost spherical with high surface areas and average size of 42 ± 9nm. EDX spectra confirmed that Ag is only the major element present and the Dynamic light scattering (DLS) assisted that the Z-average size was 203nm and 1.0 of PdI value. Zeta potential showed − 26.5mv with a single peak. The results of the biological activities of AgNPs exhibited dose dependent activity with 68.44% for arthritic, antiinflammatory with 63.32% inhibition and anti-proliferative activity illustrated IC50 value of 59.66 μg/mL expressing the potential of AgNPs to combat cancer.
  • Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets Article

    Arshad, Muhammad Sohail; Kiran, Munazza; Mudassir, Jahanzeb; Farhan, Muhammad; Hussain, Amjad; Abbas, Nasir

    Resumo em Inglês:

    Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.
  • Design and evaluation of dental pastes Containing anti-inflammatory drugs Article

    Hasan, Nadeem; Nayak, Amit Kumar; Sanaullah, Syed; Sami, Farheen; Majeed, Shahnaz; Badgujar, Vishal Bhagwan; Hasnain, Saquib; Ansari, Mohammed Tahir

    Resumo em Inglês:

    Abstract Periodontitis is an oral disease associated with inflammation and pain with swollen and bleeding gums. In the present study, dental pastes containing NSAIDs, namely, diclofenac sodium and nimesulide (1 % w/w) were prepared to treat periodontitis. Dental pastes of diclofenac sodium and nimesulide (1 % w/w) were prepared with/without mucoadhesive hydrocolloid polymers such as sodium carboxy methyl cellulose (NaCMC), hydroxyl ethyl cellulose (HEC) and methyl cellulose (MC) by conventional trituration method. The pH, drug content, viscosity, tube spreadability and tube extrudability of these prepared dental pastes were measured. These dental pastes of diclofenac sodium and nimesulide (1 % w/w) were characterized by FTIR analyses for drug-excipient compatibility. The in vitro drug releases from these dental pastes in 6.4 pH phosphate buffer solution displayed sustained release over longer period and the drug release rate was found to be decreased when the concentration of mucoadhesive polymer was increased. These dental pastes displayed good adhesion to the oral mucosa revealing more retention time in mouth when tested for ex vivo mucoadhesion using bovine cheek pouch. The stability study results reveal that the DC3 and NC3 dental paste formulations were found stable enough over a longer period in different storage conditions. The present study revealed that the prepared mucoadhesive dental pastes of diclofenac sodium and nimesulide (1 % w/w) had good adhesion with the oral mucosa to maintain consistent release of drugs over prolonged time.
  • Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns Article

    Vaz, Lilian Vieira; Balcão, Victor Manuel; Oliveira Jr, José Martins; Tubino, Matthieu; Jozala, Angela; Yoshida, Valquíria Miwa Hanai; Vila, Marta Maria Duarte Carvalho

    Resumo em Inglês:

    Abstract Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.
  • Antifungal activity of silver nanoparticles and clotrimazole against Candida spp. Article

    Meneses, María Laura; Recalde, Maite; Martin, Paula Lorena; Pardo, Alejandro Guillermo

    Resumo em Inglês:

    Abstract The aim of present study was calculate the Minimum inhibitory concentrations (MICs) of silver nanoparticles and clotrimazole for Candida species and their interaction by the adaptation of standarized methods. The MICs values of clotrimazole were 9 E-04-3 E-03 ug/ml, 0.1-0.6 ug/ml, 3 E-03- 0.1 ug/ml and 3 E-03-0.3 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. The MICs values of silver nanoparticles were 26.50- 53 ug/ml; 26.50-106 ug/ml; 106-212 ug/ ml and 26.50- 53 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. Synergism between clotrimazole and silver nanoparticles was measured by checkerboard BMD (broth microdilution) test and shown only for C. albicans susceptible to fluconazole because the fractional inhibitory concentrations (FICs) values were 0.07 - 0.15 ug/ml. Indifference was shown for the other species tested because the FICs values were between 0.5 - 2- 3.06 ug/ml. The results suggest synergistic activity depending on the fungus species analysed, however we recommend the incorporation of others measurement methodologies to confirm our results. As for measurement methodologies of MICs of silver nanoparticles and clotrimazole international normative were respected to guarantee reproducible and comparable results.
  • 99m Technetium-HMPAO-labeled platelet scan in practice: Preparation, quality control, and biodistribution studies Article

    Parvizi, Mahdieh; Farzanefar, Saeed; Khalaj, Ali; Tafakhori, Abbas; Daha, Fariba Johari; Saffar, Hana; Sadeghzadeh, Masoud; Naseri, Maryam; Ahmadzadehfar, Hojjat; Abbasi, Mehrshad

    Resumo em Inglês:

    Abstract There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.
  • Hepatoprotective and antioxidant effects of alcesefoliside from Astragalus monspessulanus Article

    Kondeva-Burdina, Magdalena; Simeonova, Rumyana; Shkondrov, Aleksandar; Krasteva, Ilina; Popov, Georgi; Manov, Vassil

    Resumo em Inglês:

    Abstract The hepatoprotective potential of alcesefoliside (AF) from Astragalus monspessulanus was investigated. Iron sulphate/ascorbic acid (Fe2+/AA) lipid peroxidation was induced in rat liver microsomes and pre-incubated with AF and silybin (100, 10 and 1 µmol). Pronounced effects were observed in 100 µmol. In vivo experiments were carried out on rats, challenged orally with carbon tetrachloride (CCl4) alone and after pre-treatment and followed by curative treatment with AF (10 mg/kg). The activity of the serum and antioxidant enzymes, together with reduced glutathione (GSH) levels and malonedialdehyde (MDA) quantity were measured. Microsomal incubation with Fe2+/AA increased MDA production. The pre-incubation with AF reduced the formation of MDA, comparable to silybin. These findings were supported by the in vivo study where CCl4-induced liver damage was discerned by significant increase in serum enzymes and in MDA production as well as by GSH depletion and reduced antioxidant enzymes activity. The AF pre-treatment and consecutive curative treatment normalizes the activity of the serum and antioxidant enzymes alike, as well as the levels of GSH and MDA. Histological examination of AF-treated livers showed a decrease in the abnormal accumulation of lipids in hepatocytes as well as reduced alterative changes in their structure in a model of CCl4-induced toxicity.
  • Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia Article

    Luo, Caikui; Wang, Yanming; Zou, Jili; Wu, Jinhu; Meng, Junhua; Zhou, Hanmin; Chen, Yonggang

    Resumo em Inglês:

    Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.
  • Analysis of potential drug interactions in medical clinic sector in a Hospital of João Pessoa - PB Article

    Costa, Jéssyca Pinheiro da; Alves, Gislayne Azevedo de Campos; Guedes, Érika da Cruz; Fonseca, Flávia Pessoa de Belmont; Souto, Rosa Águida Donosora de Melo; Lopes, Pablo Queiroz; Golzio, Adriana Maria Fernandes de Oliveira

    Resumo em Inglês:

    Abstract The objective of this study was to evaluate drug interactions based on medical records of patients hospitalized in University Hospital Lauro Wanderley (UHLW) in João Pessoa-PB, Brazil. This was a quantitative, descriptive study with a cross-sectional design. This research was conducted in the medical clinic of the above hospital by analyzing pharmaceutical intervention in medical records. The investigated samples consisted of all medical profiles with drug interaction information of patients hospitalized from June 2016 to June 2017. Most of these drug interactions were determined and classified by Micromedex® Solutions database. This research was approved by the Ethics Committee in Institutional Human Research, protocol number 2.460.206. In total, 331 drug interactions were found in 131 medical profiles. Dipyrone, enoxaparin, sertraline, ondansetron, quetiapine, tramadol, bromopride, amitriptyline, and simvastatin were medications that showed highest interactions. According to Anatomical Therapy Classification (ATC), drugs that act on the central nervous system result in more interactions. The most prevalent interaction was between dipyrone and enoxaparin. Some limitations of this study are the lack of notifications and data on drug interactions.
  • A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model Article

    Saleem, Uzma; Rasool, Talha; Ahmad, Bashir; Anwar, Fareeha; Khalid, Sana

    Resumo em Inglês:

    Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.
  • Bioprocess optimization of interferon β-1-a in Pichia pastoris and its improved inhibitory effect against hepatocellular carcinoma cells Article

    Moatamedi, Nasim; Emamzadeh, Rahman; Sadeghi, Hamid Mir Mohammad; Akbari, Vajihe

    Resumo em Inglês:

    Abstract Interferon-β-1a (INF-β-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-β-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-β- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-β-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-β-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- β-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO.
  • Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation Article

    Sartori, Gabriela Julianelly; Prado, Livia Deris; Rocha, Helvécio Vinícius Antunes

    Resumo em Inglês:

    Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.
  • Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia Article

    Zhang, Xuena; Yue, Yun; Wu, Anshi

    Resumo em Inglês:

    Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia.
  • Analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities of Pulicaria crispa (Forssk.) Oliv. (Asteraceae) Article

    Soliman, Gamal A.; Ansari, Mohd Nazam; Alqarni, Mohammed H.; Foudah, Ahmed I.; Alam, Aftab; Salkini, Mohammed Ayman; Yusufoglu, Hasan S.

    Resumo em Inglês:

    Abstract Some plants of the genus Pulicaria have been used in traditional medicines for treating back pain and inflammation. They possess various bioactivities such as antipyretic, analgesic, and hepatoprotective. This study aimed to investigate the potential analgesic, antipyretic, anti- inflammatory, and hepatoprotective activities of Pulicaria crispa (P. crispa) extract (PCE). Analgesic activity was evaluated using the hot plate and acetic acid-induced writhing tests. Antipyretic and anti-inflammatory activities were evaluated using rectal temperature and carrageenan-induced hind paw edema methods, respectively. CCl4-intoxication was used for hepatoprotective activity. Also, liver histopathology was assessed. PCE, at 500 mg/kg, exhibited significant analgesic, antipyretic, and anti-inflammatory effects. The increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin of CCl4-exposed rats reflects their liver injury. PCE significantly decreased the elevated liver markers. The hepatoprotective effect of PCE was confirmed, as it successfully reversed the altered levels of total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) in the liver tissues of CCl4-exposed rats. Histopathological studies confirmed the hepatoprotective nature of PCE. Pretreatment of rats with PCE reduced the severity of CCl4-induced liver damage. These findings concluded that PCE possesses analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities.
  • Sodium alendronate: proposal and reliability of indicators Article

    Silva, Ricardo Augusto dos Santos; Baldoni, André Oliveira; Alvim, Camila Pereira; Obreli Neto, Paulo Roque; Guidoni, Camilo Molino; Silva, Isabella Ribeiro; Figueiredo, Roberta Carvalho

    Resumo em Inglês:

    Abstract The present study proposes and evaluates the test-retest reliability of indicators of the correct use of sodium alendronate in elderly patients. This is a test-retest reliability study for use of sodium alendronate. Six questions to evaluate the correct use of this medicine were elaborated after analysis of information in the literature. Data collection was performed through questionnaires in face-to-face in-home interviews by previously trained interviewers. The participants were initially interviewed (test) when they agreed to participate in the study, and secondly (retest), after a period of 7 to 14 days from the first interview. The reliability of the questions was evaluated by means of the agreement percentage and the Kappa coefficient. Fifty-seven pairs (test-retest) were obtained. The mean age was 69.3 (SD = 6.9) years, the majority (92.5%) completed elementary education, and declared themselves white (50.9%). All the questions presented high concordance ranging from 79.0% to 98.3%. The Kappa values ranged from 0.1 (low) to 0.83 (very good). The agreement percentage and the Kappa values suggest adequate reliability of the proposed questions. We suggest that they can be used as a simple and quick way to evaluate the quality of sodium alendronate use among the elderly.
  • Role of cytochrome P450 1A2 and N-acetyltransferase 2 in 2,6-dimethylaniline induced genotoxicity Article

    Kim, Min Young

    Resumo em Inglês:

    Abstract The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor.
  • Persea americana Mill.: Evaluation of cytogenotoxicity and phytochemical prospection of leaf extracts Article

    Pastura, Danilo Giovanni Narciso; Sousa, Jaqueline das Virgens; Silva, Mayara Christine; Matos, Aline Ferreira; Santos, Hataânderson Luiz Cabral dos; Pereira, Gabriela Lopes; Rocha, Ellen Borges da; Alves, Raphael Santiago; Bastos, Leonardo de Oliveira; Pires, Lucas de Oliveira; Castro, Rosane Nora; Borba, Helcio Resende; Lima, Viviane Moreira de

    Resumo em Inglês:

    Abstract Persea americana Mill., belonging to the family Lauraceae, is noteworthy for the large amount of ethnopharmacological information in its regard, attributing to it many and varied medicinal properties. The tea and alcoholic extracts made from its leaves are used in folk medicine to treat various ailments. This study was designed to analyze the cytogenotoxicity and underlying chemistry of aqueous and hydroalcoholic extracts of avocado leaves, using the Allium cepa and micronucleus tests. The results obtained by applying the experimental models demonstrate that the extracts did not have a genotoxic effect at any of the concentrations analyzed, and even demonstrated a certain protective effect, possibly due to the presence of flavonoids and phenols, both of which are antioxidant substances. However, the extracts did present a cytotoxic effect. There were numerous karyorrhectic cells and those with nuclear alterations related to cell death. At the highest concentrations, it was possible to observe cytoplasmic alterations and binucleated cells. The extracts also caused a significant reduction in the number of cells undergoing division. These effects can be a response to the phytochemical agents present in the extracts. The results suggest that the extracts contain bioactive components that deserve further studies related to cancer therapies.
  • Spending Estimates for Gastric Cancer in Central Brazil Article

    Pontes, Jaqueline Correia; Pontes, Jordão Correia; Silva, Lucas Luiz de Lima; Moraes Filho, Aroldo Vieira de; Bitencourt, Carla Afonso; Itria, Alexander; Carneiro, Lilian Carla; Barbosa, Mônica Santiago

    Resumo em Inglês:

    Abstract Stomach cancer is the second leading cause of death by cancer worldwide and is even more pronounced in South America. In Brazil, it is estimated that an increase in the number of cases due to this cancer occurred in the biennium 2018-2019. In this study, we investigated the expenditures of the State Health Department of Goiás on hospitalizations and treatment of gastric cancer for the Unified Health System (SUS) from 2008-2016. This is a cross-sectional, descriptive, and analytical study based on secondary data from the Unified Health System computing department (DATASUS) and the System of Management of the Table of Procedures, Medications, Orthosis, Prosthesis, and Special Materials of SUS through CONECTA-SUS related to International Classification of Diseases-10/C16 (ICD-10/C16) procedures for gastric neoplasms. A total of I$ 5,697,958.20 was spent on gastric tumor in the last nine years in Goiás, I$ 4,492,916.67 (0.3%) on hospitalizations, and I$ 1,997,120.91 on treatment. This study presents a current and relevant estimate of the costs of gastric cancer patients in Goiás. Moreover, we provide information on the extent of the cancer issue to public health. Our analysis offers components for service management and studies that reduce resource allocation in more rational ways.
  • Biological activities of essential oils from six genotypes of four Ocotea species Article

    Rambo, Michele Andréia; Soares, Krissie Daian; Danielli, Letícia Jacobi; Lana, Daiane Flores Dalla; Bordignon, Sérgio Augusto de Loreto; Fuentefria, Alexandre Meneguello; Apel, Miriam Anders

    Resumo em Inglês:

    Abstract Essential oils from four Ocotea species collected in southern Brazil were evaluated for chemical composition using gas chromatography coupled with mass spectrometry. The primary compound identified in O. acutifolia essential oil was an unsaturated tetracyclic diterpene, phyllocladene (67.7%), followed by a sesquiterpene hydrocarbon, β-selinene (18.0%). The sesquiterpene fraction was predominant in oils from two collections of O. puberula; β-caryophyllene (25.2%) and globulol (22.6%) were the major compounds identified in collections 1 and 2, respectively. O. silvestris essential oil contained predominantly germacrene D and bicyclogermacrene. These compounds were also predominant in essential oil from O. indecora leaves collected from shady habitats. By contrast, essential oil extracted from O. indecora grown under direct sunlight contained mainly oxygenated sesquiterpenes, such as guaiol (30.2%), α-eudesmol (27.6%), and β-eudesmol (12.7%). Chemotaxis assays showed that Ocotea essential oils had no significant inhibitory activity on leukocyte migration compared with a chemotactic stimulant (lipopolysaccharide from Escherichia coli). However, the oils exhibited antifungal activity against Candida parapsilosis, with a minimum inhibitory concentration of 500 µg/mL. To our knowledge, this is the first study to investigate the in vitro antifungal and antichemotactic activities of essential oils from Ocotea species native to southern Brazil.
  • Enhanced photodynamic therapy of TiO2/N-succinyl-chitosan composite for killing cancer cells Article

    Ma, Min; Cheng, Lu; Wang, Ling; Liang, Xingxing; Yang, Linjiao; Zhang, Aiping

    Resumo em Inglês:

    Abstract The aim of this study was to investigate the effect of TiO2/N-succinyl-chitosan composite (TiO2/ NSCS) photodynamic therapy (PDT), while considering the effects of various light sources on the activation of photosensitizer. The methyl thiazolyl tetrazolium assay was used to examine the cell survival rate of the cells. The results showed that glioma cell strain (U251) was the most sensitive cancer cell strain to TiO2/NSCS. When the concentration of TiO2/NSCS was between 0 and 800 μg·mL-1, there was no obvious cytotoxicity to normal liver cells (HL-7702) and U251 cells. During the PDT process, the photokilling effect of TiO2/NSCS on U251 cells under ultraviolet-A (UVA) light irradiation was stronger than that of pure TiO2, and its killing effects were positively correlated with concentration and irradiation time. In addition, both UVA and visible light could excite TiO2/ NSCS, which had significant killing effect on U251 cells. The results of acridine orange/ethidium bromide fluorescent double staining and Annexin V/propidium iodide double staining indicated that TiO2/NSCS under UVA and visible light irradiation could kill U251 cells by inducing apoptosis, and the apoptosis rate of TiO2/NSCS treatment groups was higher than that of TiO2 treatment groups. Therefore, TiO2/NSCS might be used as a potential photosensitizer in PDT.
  • In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS Article

    Zhang, Ying; Pi, Jiaxin; Li, Wen; Zhang, Ludan; Ma, Xutong; Kebebe, Dereje; Qi, Dongli; Li, Nan; Guo, Pan; Liu, Zhidong

    Resumo em Inglês:

    Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion.
  • In Vitro Evaluation of Dalbergia sissoo and Acacia modesta gum as Pharmaceutical Binders for Drug Delivery System Article

    Munir, Hira; Shahid, Muhammad; Sharif, Sumaira

    Resumo em Inglês:

    Abstract The present study aimed to compare the crude, modified and hydrolyzed gums of Dalbergia sissoo and Acacia modesta as a biodegradable binder for drug delivery system using acetaminophen as a model drug. The physiochemical properties such as pH, fluorescence analysis and swelling index were determined. The gums were hydrolyzed and modified. Acetaminophen tablets were prepared using wet granulation technique and the gum solutions were used as a binder. Hydroxypropyl methylcellulose was used as a synthetic binder. Different properties of granules and tablets were evaluated. Results showed that both gums were acidic in nature, while D. sissoo and A. modesta showed light brown and creamy color in fluorescence analysis. The swelling ratio was the highest in water followed by 0.1N HCl and least in phosphate buffer. The prepared tablets showed faster and slower dissolution profiles in the same dissolution system. The crude gums have the highest dissolution rate, and this rate was decreased in the case of modified and hydrolyzed gums samples. The crude gums showing slower release can be useful in sustained-release tablets, while the modified gums having faster release rate are helpful in conventional tablet formulation. Taken together, the selected gums could be a good model for evaluation as a binder or hydrophilic polymer in tablet formulation.
  • In vitro assessment for cytotoxicity screening of new antimalarial candidates Article

    Espíndola, Mariana Rodrigues; Varotti, Fernando de Pilla; Aguiar, Anna Caroline Campos; Andrade, Silmara Nunes; Rocha, Eliana Maria Mauricio da

    Resumo em Inglês:

    Abstract In antimalarial research there are no standard procedures to determine the toxicity of a drug candidate. Among the alternatives available, in vitro cytotoxicity assays are the most widely used to predict toxic effects of future therapeutic products. They have the advantage over the in vivo assays, in that they offer the possibility to restrain the number of experimental variables. The objective of the present study was to compare in vitro cytotoxic methods by testing various compounds currently used to treat malaria against different cell lines. Neutral red (NR) uptake and methylthiazoletetrazolium (MTT) colorimetric in vitro assays were used to determine preliminary toxicity of commercially available antimalarial drugs against tumor and non-tumor cells lines. Toxicity through brine shrimp lethality bioassay and hemolytic activity were also evaluated. Significant differences were observed in the tests measured by NR uptake. The tumor cell lines TOV-21G and HepG2 and non-tumor WI-26VA4 cells showed relatively uniform toxicity results, with TOV-21G being the most sensitive cell tested, presenting the lowest concentration to cause death to 50% of viable cells (CC50) values. The results of this study support the use of TOV-21G, HepG2 and WI-26VA4 cells lines as the choice for cytotoxicity tests to evaluate potential bioactive compounds.
  • A Selective Fluorescent Probe for the Determination and Imaging of Fluoride in Living Cells Article

    Cui, Xuejun; Wang, Xingong; Lin, Xiaoyan; Liang, Yanchao

    Resumo em Inglês:

    Abstract Fluoride anions are indispensable trace elements required for sustaining life. To investigate the homeostasis and action of fluoride in the body, a new highly sensitive and selective fluorescence detection method was designed for fluoride in aqueous solutions. A fluorescent probe for fluoride (FP-F) was synthesized for imaging F- in living cells. The design strategy for the probe was based on the specific reaction between fluoride and silica to mediate deprotection of this probe to fluorescein. Upon treatment with F-, FP-F, a closed and weakly fluorescent lactone, was transformed into an open and strongly fluorescent product. Under the optimum conditions, the detection limit for fluoride was 0.526 nM. FP-F could detect micromolar changes in F- concentrations in living cells by confocal microscopy.
  • Solid Phase Extraction and Simultaneous Chromatographic Quantification of some Non-steroidal Anti-inflammatory Drug Residues; an Application in Pharmaceutical Industrial Wastewater Effluent Article

    Korashy, Mohamed A. R.; Gawad, Sherif A. Abdel; Hassan, Nagiba Y.; AbdelKawy, M.

    Resumo em Inglês:

    Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 μm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction.
  • Potentially inappropriate medication use in a comprehensive therapy management service: clinical outcomes and interventions Article

    Martins, Ursula Carolina de Morais; Ramalho-de-Oliveira, Djenane; Nascimento, Mariana Martins Gonzaga do; Nascimento, Yone Almeida; Oliveira, Grazielli Cristina Batista de; Cid, Annaline Stiegert; Lima, Marina Guimarães

    Resumo em Inglês:

    Abstract This study aimed to describe potentially inappropriate medication (PIM) use according to the Beers criteria among older adults followed in a comprehensive medication management (CMM) service, the pharmacists´ interventions, and the clinical outcomes of PIM use. All older adults in a CMM service delivered in the Brazilian public primary care system were included in the study (n = 389). Two methodological approaches were developed: (I) cross-sectional - prevalence of PIM use and associated factors were identified (univariate analysis - Pearson’s chi-square; multivariate - logistic regression); (II) documental analysis of the negative clinical outcomes potentially associated with PIM use and pharmacists’ interventions. The prevalence of PIM use was 48.3%, and it was independently and positively associated with the use of ≥ 5 drugs. For 21.3% of PIMs, a potential negative clinical outcome was identified. The most common negative clinical outcome was hypotension (35.1% of the negative outcomes), fractures or diagnosis of osteoporosis (21.1%), and hypoglycemia (14.0%). For most of them (78.9%), an intervention was performed to mitigate harm or discontinue use. A high prevalence of PIM was detected and was associated with polypharmacy. A significant proportion of PIM showed potential negative clinical outcomes that were identified by clinical pharmacists, and the majority of pharmacists’ interventions aimed at its mitigation or deprescription. Overall, our findings reinforce the potential of CMM services for reducing PIM use and the occurrence of negative outcomes.
  • Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity Article

    Ouyang, Yong; Meng, Fansu; Du, Manling; Ma, Qianqian; Liu, Hui; Zhuang, Yong; Pang, Mujuan; Cai, Tiange; Cai, Yu

    Resumo em Inglês:

    Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.
  • The effects of pharmacist interventions on health outcomes in patients with advanced prostate cancer in Brazil Article

    Aguiar, Patricia M; Mori, Ana Luiza PM; Lima, Maria GF de; Rossi, Magali SPN; Nicoletti, Maria Aparecida; Martins, Karina OF; Lopes, Ana Lúcia M; Coan, Teresa Cristina M; Fugita, Oscar Eduardo H; Storpirtis, Sílvia

    Resumo em Inglês:

    Abstract This study examined the effects of pharmacist interventions for patients with advanced prostate cancer. A pre-post study was conducted between October 2014 and August 2017 in a community pharmacy in Brazil for outpatients with advanced prostate cancer, aged ≥ 18 years, using cyproterone acetate and/or goserelin. The patients had face-to-face meetings with a pharmacist who dispensed antiandrogenic drugs and performed interventions aimed at solving and/or preventing drug-therapy problems. Primary outcomes regarding prostate-specific antigen (PSA) and testosterone levels were compared at 0, 6, and 12 months, whereas secondary outcomes-medication adherence and quality of life-were compared at baseline and at the 12-month follow-up. Medication adherence was assessed using the Morisky-Green test, and quality of life was measured by the Medical Outcomes Study 36-item Short Form (SF-36) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The analysis included 20 patients; 311 drug-therapy problems were identified and most of them were related to adverse reactions (78.5%). The most common adverse reactions were reduced libido, erectile dysfunction, hyperglycemia, fatigue, and gynecomastia. Testosterone levels significantly decreased at 6 months, and PSA levels at 6 and 12 months. No significant changes in adherence were noted at the end of the study. A significant increase in the “pain” domain and an improvement trend in the “physical aspects” and “vitality” domains were observed based on the SF-36 instrument. The findings show that pharmacist interventions were able to improve PSA and testosterone levels, and some domains of quality of life of patients.
  • Medication errors in critical patients during medication reconciliation: analyses and clinical management Article

    Adriano, Liana Silveira; Ibiapina, Juliana Ribeiro; Romero, Nirla Rodrigues; Lima, Alisson Menezes Araújo; Ponciano, Ângela Maria de Souza; Fonteles, Marta Maria de França

    Resumo em Inglês:

    Abstract Medication errors (ME) are frequent in the admission of patients to the ICU and can be identified and prevented through medication reconciliation (MR). Our aim was to evaluate the incidence, type and severity of MEs and associated factors, identified during MR in the ICU. This is a prospective, analytical approach, performed in the ICU of a private hospital, where the MRs were evaluated from April to June 2016. The SPSS and Stata programs were used to analyse the data. Logistic regression was performed to determine the factors associated with MEs. MR was performed with 136 patients, of whom 126 (92.6%) used drugs regularly. The incidence of MEs was 16.3% (95% CI 11.5-21.2). The main classes of drugs involved were those acting on the nervous and cardiovascular systems. There were 128 pharmaceutical interventions (acceptance: 71.1%). Regarding severity, 65.5% (n=80) of the errors reached the patient, but there was no harm. The risk factors for MEs identified were: age ≥60 years, number of comorbidities >1 and previous use of drugs ≥9. The incidence of MEs found and the significant association with age, comorbidities and polymedication alert to the need for specific attention to prevent admission errors in the most susceptible patient groups.
  • DEVELOPMENT, IN-VITRO AND EX-VIVO EVALUATION OF MUCO-ADHESIVE BUCCAL TABLETS OF HYDRALAZINE HYDROCHLORIDE Article

    Samanthula, Kumara Swamy; Kumar CB, Mahendra; Bairi, Agaiah Goud; Satla, Shobha Rani

    Resumo em Inglês:

    Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.
  • Use of microalgal biomass as functional ingredient for preparation of cereal based extrudates: impact of processing on amino acid concentrations and colour degradation kinetics Article

    Ananthanarayan, Laxmi; Kumar, Vikas; Panghal, Anil; Singh, Barinderjit; Waghmare, Roji; Gat, Yogesh; Kaur, Narinder

    Resumo em Inglês:

    Abstract Suitability of developing Spirulina incorporated cereal based low cost nutritious extrudates was analysed against extrusion processing parameters. Most significant extrusion processing parameters considered for present study were feed moisture (20-25%), die temperature (100-120 °C) and screw speed (50-100 rpm). Different extrusion conditions were used to obtain most acceptable rice: Spirulina blend extrudates. In present study before extrusion processing different additives (citric acid and sodium bicarbonate) were added in rice: Spirulina blend and checked its effect on colour degradation kinetics at varied packaging and storage conditions. Higher screw speed (100 rpm) indicating less residence time of feed material inside the barrel resulted in higher colour retention of rice: Spirulina (97:03) blend extrudates. Kinetics for rice: Spirulina (97:03) blend extrudates indicates faster rate of colour degradation in terms of lightness (half-life of 4 days) when packed in metalized polyethylene at 50°C with 65% relative humidity. Increased concentration of Spirulina (1-3%) in raw formulations resulted in increase in concentration of all amino acids. Impact of extrusion processing has shown non-significant (p ≤ 0.05) effect on amino acid concentrations of rice: Spirulina blend extrudates. Also, all the spirulina added samples showed good consumer acceptability with the score of 6.7.
  • Supplementation with β-carotene aids minimize inflammation in monosodium urate crystal- induced gouty arthritis in Wistar albino rats Article

    Udhaya, Lavinya B; Ubrewe Rutera, Aline; Ram Kumar, K; Sangeetha, N; Manisha, P; Prince, Sabina Evan

    Resumo em Inglês:

    Abstract Gout is a form of metabolic arthritis originated on grounds of increased accumulation of monosodium urate (MSU) crystals in joints. Current study focuses on anti-arthritic activities of β-carotene on MSU crystal-induced gouty arthritis rats in comparison with the non-steroidal anti-inflammatory drug, indomethacin. The evaluation was done by taking into account paw oedema, lysosomal enzymes, anti-oxidant enzymes, lipid peroxidation, serum biochemical parameters (uric acid, creatinine), serum cytokines (TNF-α, IL-1β) and histopathological studies. After the induction of MSU crystals, the lysosomal enzymes were increased, antioxidant enzymes were reduced, lipid peroxidation increased and paw volume increased. β-carotene treated at a dose of 10 mg/kg of body weight stabilizes lysosomal enzymes, increases anti-oxidant enzymes, regulates lipid peroxidation and decreased paw volume. The drug β-carotene potentially influences anti-inflammatory effects in arthritic group which is evident from the reduction in the elevated levels of inflammatory cytokines, TNF-α and IL-1β. Current study is an evidence of anti-inflammatory and anti-oxidant effects of β-carotene against MSU-crystal induced gouty arthritis rats.
  • Evaluation of pharmaceutical care in Brazilian primary health services settings: expanding objects and approaches Article

    Soares, Letícia Santana da Silva; Mata, José Antonio Iturri de La; Santana, Rafael Santos; Galato, Dayani

    Resumo em Inglês:

    Abstract The objective of this work is to reflect on the objects and approaches usually employed in the evaluation of pharmaceutical care and their potential applicability in primary care settings. We conducted the review of the literature, and, to exemplify the advantages of expanding these objects and approaches, a real-world problem situation was selected: morbidity and mortality related to lack of treatment adherence by hypertensive patients in Brazilian primary health care services. Our reflections highlight the need to evaluate the effects of interventions, understood within Donabedian’s normative model as ‘outcomes,’ which can be clinical, humanistic, or economic. Our findings show that most published studies, even those that set out to report outcomes, actually evaluate processes, such as number of visits, number of problems identified, types of problems, or acts of the practice performed by pharmacists. On the other hand, we also identify a need for study designs and indicators to enable ‘finer’ normative assessment. We also discuss the importance of shifting research toward an evaluative paradigm to allow strategic, logic, effects, production, efficiency, and implementation analyses. Finally, we suggest some possible indicators to evaluate pharmaceutical care interventions in the selected problem situation, through an extension of the objects and approaches proposed.
  • Blockage of TGF-β1-induced epithelial-to- mesenchymal transition by oxymatrine prevents renal interstitial fibrosis Article

    Li, Li; He, Dongyuan; Cai, Qin; Wang, Dong-ying

    Resumo em Inglês:

    Abstract Most chronic kidney disease inevitably progress to renal fibrosis. Tubular epithelial- to-mesenchymal transition (EMT) is recognized to play major roles in renal fibrosis. Oxymatrine (OM) is a major alkaloid component found in a Chinese herb Sophora roots and has many effects. The aim is to investigate the effect of OM on renal tubular EMT and elucidate its mechanism. Mice underwent unilateral ureteral obstruction (UUO) followed by intraperitoneal injection of OM (120 mg/kg) or control vehicle. Human kidney proximal tubular cell line (HK-2) was used and EMT was induced with 5 ng/mL of transforming growth factor-β1 (TGF-β1). In vivo, renal tubulointerstitial fibrosis was induced and E-cadherin was down-regulated, while the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), TGF-β1 and its type I receptor (TGF-βRI) were up-regulated in UUO mice. In contrast, OM significantly ameliorated renal fibrotic lesions and attenuated the expressions of FN, α-SMA, TGF-β1 and TGF-βRI, but increased E-cadherin in the obstructed kidneys. In vitro, OM abolished TGF-β1-mediated E-cadherin suppression and FN, α-SMA and TGF-βRI induction in HK-2 cells in a dose-dependent manner. These observations strongly suggest that the renal protective effects of OM could be mediated by prevention of EMT and manifested as suppression of TGF-β1 and TGF-βRI expressions.
  • Nanoformulations of quercetin: a potential phytochemical for the treatment of uv radiation induced skin damages Articles

    Tripathi, Nancy; Verma, Surajpal; Vyas, Manish; Yadav, Narendra Singh; Gain, Subhajit; Khatik, Gopal Lal

    Resumo em Inglês:

    Abstract The continuous prolonged exposures of sun light especially the ultra violet (UV) radiation present in it, cause not only the risk of skin cancer but also it may cause premature skin aging, photodermatoses and actinic keratoses. Flavonoids (including Flavane, Flavanone, Flavone, Flavonol, Isoflavone, Neoflavone etc.) having potent antioxidant activity, used as topical applications for protection against UV induced skin damages as well as for skin care. Most commonly used flavonoid is quercetin (Flavonol), which is present in fruits, vegetables, and herbs. We aim to review the research focused on development of different novel formulations to treat UV radiations induced skin diseases. In this review, several formulations of flavonoid quercetin were discussed and their outcomes were compiled and compared in context to solubility, stability and efficiency of application. On the basis this comparative analysis we have concluded that three formulations, namely glycerosomes, nanostructured lipid carriers and deformable liposomes hold good applications for future aspects for topical delivery of quercetin. These formulations showed enhanced stability, increased quercetin accumulation in different skin layers, facilitated drug permeation in skin and long-lasting drug release.
  • New and potential properties, characteristics, and analytical methods of ferulic acid: A review Article

    Marcato, Danieli Camilo; Spagnol, Caroline Magnani; Salgado, Hérida Regina Nunes; Isaac, Vera Lucia Borges; Corrêa, Marcos Antonio

    Resumo em Inglês:

    Abstract Phenolic compounds are widely distributed in the plant kingdom and in the microorganisms. Cinnamic acid and its hydroxylated derivative-ferulic acid, are phenolic compounds. Ferulic acid possesses antioxidant potential, as well as anti-cancer, anti-inflammatory, and antimicrobial properties. It prevents the harmful effects of radiation both as an ultraviolet absorber and as a free radical scavenger; it is not cytotoxic. Although ferulic acid has beneficial properties, it is hardly used in cosmetic preparations and has been rarely studied in the literature. Herein, we review the literature on ferulic acid, to provide information which can contribute to further research on the compound.
  • Nutritional properties, aromatic compounds and in vitro antioxidant activity of ten date palm fruit (Phoenix dactylifera L.) varieties grown in Tunisia Article

    Saafi, Emna Behija; Arem, Amira El; Chahdoura, Hassiba; Flamini, Guido; Lachheb, Belgacem; Ferchichi, Ali; Hammami, Mohamed; Achour, Lotfi

    Resumo em Inglês:

    Abstract Phoenix dactylifera L. has traditionally been used as a medicine in many cultures. The aim of this study was to evaluate the nutritional properties, aromatic compounds, total phenolic content and the antioxidant activity of ten ripe date fruit varieties grown in Tunisia. Sugar profiles were analyzed by high performance liquid chromatography, while fatty acid compounds were detected by gas chromatography and aromatic compounds were analyzed by GC-Electron Impact Mass Spectroscopy. Total phenolic contents were measured using colorimetric methods, whereas antioxidant capacities were evaluated in vitro using DPPH and ABTS radicals. It has been found that total sugars are the predominant component in all date varieties, followed by moisture, along with moderate amounts of proteins, ash, and fats. Multivariate tests based on the volatile compounds profile showed significant differences among varieties. Between the sixty-two volatile compounds detected, alcohols, aldehydes and unsaturated hydrocarbons constituted the main chemical classes. The date varieties exhibited strong antioxidant potential that correlated with phenolic content. In conclusion date varieties can play a major role in human nutrition and health because of their wide range of valuable nutritional components and natural antioxidants that could potentially be considered as a functional food ingredient.
  • Combination effect of doxorubicin and HIF inhibitor on MCF-7 CD44+/CD24- subpopulation cells in hypoxic condition Article

    Rasouli, Azadeh; Aliebrahimi, Shima; Montazeri, Vahideh; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser

    Resumo em Inglês:

    Abstract Hypoxia-inducible factors (HIFs) and cancer stem cells (CSCs) are two challenging causes of radiotherapy and chemotherapy resistance, leading to most cases of failure and recurrence in breast cancer therapy. This study was conducted to investigated the inhibitory effect of combination therapy with doxorubicin (an anthracycline) and FM19G11 (an HIF inhibitor) on MCF-7 cells and their CSC-like cells (CSC-LCs). MCF-7 CSC-LCs with a CD44+/CD24- phenotype were sorted and characterized by flow cytometry. A combination of doxorubicin and FM19G11 caused more cytotoxic effects on MCF-7 and CSC-LCs compared to doxorubicin monotherapy. The largest synergistic effect was observed in CSC-LCs under hypoxic conditions; however, MCF-7 cells showed no synergism in normoxic conditions. The administration of doxorubicin and FM19G11 induced late apoptotic and necrotic cell death in MCF-7 and CSC-LCs. Additionally, G2 phase arrest was observed in both cells. Our results demonstrated that co-administration of FM19G11 and doxorubicin had a synergistic effect in hypoxia and improved drug resistance in breast cancer stem cells.
  • Effect of non-nucleoside reverse transcriptase inhibitors and protease inhibitors on serum levels of myeloperoxidase and C-reactive protein in HIV-infected individuals Article

    Borato, Danielle Cristyane Kalva; Kalva-Filho, Carlos Augusto; Machado, Edneia Peres; Barbosa, Cristiane Rickli; Vellosa, José Carlos Rebuglio

    Resumo em Inglês:

    Abstract It remains unclear whether increased inflammatory and cardiovascular risk biomarkers differ depending on the class of antiretroviral that is used. This study evaluated the plasma levels of inflammatory and cardiovascular risk biomarkers, such as MPO, hs-CRP, glucose, lipid profile, ALT (GPT), AST (GOT), urea and creatinine, as well as the blood count, of all the 164 participants in the study, either infected or un-infected with HIV. Thirty of the 104 HIV-infected individuals did not receive any antiretroviral; twenty-four of them were treated with non-nucleoside reverse transcriptase inhibitor class; and fifty took protease inhibitors. The control group consisted of sixty non-HIV infected individuals. In the case of the HIV-infected volunteers, the CD4+ T lymphocyte counts and viral load were also analyzed. Regardless of the hematological and biochemical changes resulting from the antiretroviral therapy (ART), the MPO and hs-CRP values significantly increased for the HIV-infected individuals (treated or untreated), irrespective of the class of ART that was used. This is important because these biomarkers are designed to be predictors of the risk of cardiovascular disease. The results of this study provide supporting evidence for the hypothesis that HIV-infected individuals are at increased risk of developing cardiovascular disease related to chronic inflammations, despite virological control with ART, and regardless of the class of ART that is used.
  • Synthetic berberine derivatives as potential new drugs Article

    Filli, Mensura Sied; Ibrahim, Ahmed Abdalla; Kesse, Samuel; Aquib, Md; Boakye-Yiadom, Kofi Oti; Farooq, Muhammad Asim; Raza, Faisal; Zhang, Yubin; Wang, Bo

    Resumo em Inglês:

    Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.
  • Effects of reducing postprandial hyperglycemia and metabolism of acetate wheat starch on healthy mice Article

    Toan, Nguyen Van Thanh; Thuy, Phan Kim; Hien, Chu Thi Thu; Chau, Thai Khoa Bao; Tien, Nguyen Huu; Dung, Tran Huu

    Resumo em Inglês:

    Abstract Recently, the acetate wheat starch (AWS) has been prepared by acetylation with an acetyl content of 2.42%, containing of rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS) with 25.0%; 22.9% and 34.5%, respectively. In this study, this kind of starch was continuously evaluated with the postprandial blood glucose response and determined short-chain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. The result showed that the mice fed with AWS exhibited a very limited increase in blood glucose level and remained stable for 2 hours after meals efficiently comparing with the control group fed with natural wheat starch (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed with AWS was significantly higher than mice fed with NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Thus, AWS has shown to limit the postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs providing a part of energy for the body’s activities, avoiding rotten fermentation causing digestive disorders which are inherent restrictions of normal high cellulose and fiber food.
  • Hypolipidemic properties of the extracts of Belamcanda chinensis leaves (BCLE) in KK-A y mice Article

    Guo, Ying; Dai, Rongji; Deng, Yulin; Sun, Lili; Meng, Shiying; Xin, Nian

    Resumo em Inglês:

    Abstract The extract of Belamcanda chinensis leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of diabetes-related hyperlipidemia in Hainan province, South China. In this study, the lipid-decreasing effects of BCLE on obese diabetes were investigated on KK-Ay mice. The component F2 ameliorated lipid disorder, as indicated by decreased levels of body weight, liver index, levels of TC, TG and LDL-c in the serum and liver. The enhancement effect of F2 on liver SOD and the inhibitory effect of F2 on MDA demonstrated that F2 exhibited significant antioxidant activity on liver injury. F2 also prevented vacuolar degeneration and reduced pathological tissue injury in liver. In addition, the component F1 decreased the levels of TG, LDL-c and MDA in the liver. These findings suggest that F2 may have therapeutic potential in the prevention and therapy of hyperlipemia and liver disease associated with obesity-related diabetes.
  • Reflection about the hemodialysis water microbiological quality in Brazil Article

    Carvalho, Gabriela Corrêa; Dua, Kamal; Gupta, Gaurav; Bugno, Adriana; Pinto, Terezinha de Jesus Andreoli

    Resumo em Inglês:

    Abstract Dialysis has been widely used in the treatment of patients with chronic kidney diseases and is considered a global public health issue. This treatment, which has changed the prognosis and quality of life in patients with chronic renal failure, can lead to complications that are often fatal. For this reason, there is a need for validation of alternative tests that favor the monitoring of treated water for dialysis in real-time to promote and prevent injuries to patients submitted to this procedure.
  • Atorvastatin suppresses lipopolysaccharide-induced inflammation in human coronary artery endothelial cells Article

    Tian, Zhen; Li, Zhitao; Guo, Tian; Li, He; Mu, Yanshuang

    Resumo em Inglês:

    Abstract The present study was designed to examine the effects of atorvastatin on vascular inflammatory responses in human coronary artery endothelial cells(HCAECs), when challenged by lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) ligand. HCAECs were pretreated with atorvastatin and induced by LPS. The expression of TLR4, interleukin -6(IL-6), monocyte chemoattractant protein 1(MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecular-1(ICAM-1), nuclear factor-κB (NF-κB) and p38 mitogen activated protein kinase(p38 MAPK) were evaluated using Real-time polymerase chain reaction, cytokine ELISA assay and Western blotting. The results showed that pretreatment with atorvastatin down-regulated the expression of TLR4 in LPS-activated HCAECs. Atorvastatin also attenuated the LPS-induced expression of interleukin IL-6 and MCP-1, at both the transcription and translation level in HCAECs. LPS-induced endothelial cell adhesion molecules, ICAM-1 and VCAM-1 expression were also reduced by pretreatment with atorvastatin. Furthermore, atorvastatin efficiently suppressed LPS-induced phosphorylation of NF-κB and p38 MAPK in HCAECs. These findings show that atorvastatin suppresses endothelial cell inflammation, suggesting that atorvastatin may be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.
  • The effects of boric acid and quercetin on contrast media-induced nephropathy in rats Article

    Yilmaz, Kenan; Yazici, Selcuk; Ozcan, Teoman; Altun, Eren

    Resumo em Inglês:

    Abstract We aimed to determine the effects of boric acid and quercetin on contrast media-induced nephropathy in rats. Thirty-two rats were divided into four equal groups with eight rats in each group: the control (C) group, contrast media (CM) group, contrast media plus boric acid (CMB) group, and contrast media plus quercetin (CMQ) group. Boric acid (H3(BO)3, 4% solution) at a dose of 200 mg/kg was administered by oral gavage to rats in the group CMB once daily for 4 consecutive days (days 1 to 4). Quercetin at a dose of 50 mg/kg was administered by oral gavage to rats in the CMQ group once daily for 4 consecutive days (days 1 to 4). A significant decrease was found in the serum urea and creatinine levels in the CMQ group compared with the CM group (P <0.01). The serum nitrite and nitrate levels were higher in the CM group than in the C group and were lower in the CMQ group than in the CM group (P <0.01). A significant decrease in the severity of tubular necrosis was found in the CMQ group compared to the CM group (P <0.05). Quercetin had protective effects against contrast nephropathy, but no beneficial effect of boric acid was found.
  • A study on alpha-terpineol in Alzheimer’s disease with the use of rodent in vivo model, restraint stress effect and in vitro Amyloid beta fibrils Article

    Alipour, Hamid-Reza; Yaghmaei, Parichehreh; Ahmadian, Shahin; Ghobeh, Maryam; Ebrahim-Habibi, Azadeh

    Resumo em Inglês:

    Abstract Alzheimer’s disease (AD) is a neurological disorder in which the neuronal degeneration is associated with inflammatory processes and oxidative stress. Since alpha-terpineol was shown to possess antioxidant and anti-inflammatory effects, the administration of this compound was studied on a rat model of AD. To create this model, Aβ1-42 was injected into the hippocampus of male Wistar rats. Generated AD models were divided into simple AD models and AD models in which short-term immobilization stress was added. Preventive and therapeutic (post-AD induction) effects of alpha-terpineol consumption (100 mg/Kg) were subsequently investigated in AD models, which were compared with control groups. Biochemical factors (superoxide dismutase and malondialdehyde), histological manifestations (amyloid plaques and neuron counts) and possible memory impairment (shuttle-box experiment) were investigated in all groups. For the in vitro experiment, alpha-terpineol effect was checked on Aβ1-42 fibril formation. In preventive and therapeutic modes, alpha-terpineol consumption could improve neurogenesis and long-term memory while reducing amyloid plaque counts and ameliorating biochemical factors (higher levels of superoxide dismutase and malondialdehyde and reduced levels of MDA). In vitro, shorter fibrillar structures were formed in the presence of alpha-terpineol, which indicates an anti-amyloid effect for this compound. In conclusion, alpha-terpineol significantly counteracted AD consequences.
  • Optimisation of asarone removal from Piper sarmentosum Roxburgh leaves using supercritical carbon dioxide extraction: the Box-Behnken design Article

    Hamil, Mohd Shahrul Ridzuan; Mohamed, Nornisah; Ismail, Zhari

    Resumo em Inglês:

    Abstract Piper sarmentosum is a herbaceous shrub with numerous pharmacological benefits. However, the presence of two toxic phenylpropanoids (α- and β-asarone) limits the medicinal usage of the plant. In this study, the extraction of three asarone isomers, namely α-, β-, and -asarone was optimised using supercritical carbon dioxide extraction (SC-CO2) combined with Box-Behnken experimental design. Comparison of asarone contents in different conventional solvent extracts of P. sarmentosum leaves prior to and after SC-CO2 extraction was performed. The SC-CO2 method successfully maximised the extraction of α-, β-, and ɣ-asarone at P = 81.16 bar, T = 50.11°C, and t = 80.90 min, yielding 13.91% α-asarone, 3.43% β-asarone, and 14.95% ɣ-asarone. The SC-CO2 residue of the leaves re-extracted with conventional solvents showed a significant decrease of asarone ranging from 45% to 100% (p<0.001) compared to their counterparts without SC-CO2 treatment. α-, β-, and ɣ-asarone were completely removed in the ethanol extract of the residue. These findings suggested that the optimised SC-CO2 extraction parameters may serve as a quick treatment step for the selective removal of asarone from P. sarmentosum to develop safer extracts for the food and nutraceutical industries applications.
  • Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts Article

    Vishwakarma, Vishal Kumar; Upadhyay, Prabhat Kumar; Gupta, Jeetendra Kumar; Srivasata, Ritesh Kumar; Ansari, Tarique Mahmood

    Resumo em Inglês:

    Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff’s apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.
  • Chrysin-Enhanced Cytotoxicity of 5-Fluorouracil-Based Chemotherapy for Colorectal Cancer in Mice: Investigating its Effects on Cyclooxygenase-2 Expression Article

    Yosefi, Sedighe; Pakdel, Abbas; Sameni, Hamid Reza; Semnani, Vahid; Bandegi, Ahmad Reza

    Resumo em Inglês:

    Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.
  • Alleviation of neuropathic pain by trazodone in rats Article

    Vasudevan, Rajalakshimi; Kandasamy, Geetha; Almaghaslah, Dalia; Almanasef, Mona; Alqahatani, Ali; Aldahish, Afaf; Venkatesan, Krishnaraju; Paulsamy, Premalatha; Maheswari, C; Wahab, Shadma

    Resumo em Inglês:

    Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.
  • Desirability Function in analytical method development for determination of glitazones and metabolites employing HF-LPME Article

    Silva, Matheus Santiago da; Calixto, Greyce Kelly Steinhorst; Oliveira, Débora Cristina de; Lourenço, Felipe Rebello; Calixto, Leandro Augusto

    Resumo em Inglês:

    Abstract Thiazolidinedione, often shortened to TZD or glitazone, helps lower insulin resistance, which is the underlying problem for many people with type 2 diabetes. The two most known glitazones are pioglitazone (PGZ), with the brand name medicine Actos®, and rosiglitazone (RSG), which is Avandia®. This study presented a multivariate optimization in the microextraction procedure employing Fractional Factorial Design (FFD) combined with Desirability Function (DF) to determine TZD and metabolites in biological samples. Microextraction requires several parameters to be optimized; however, most of them still use univariate optimization. Finding optimum conditions by simple response is relatively simple, but the problems, in case of microextractions, are often more complex when it has more responses. For example, changing one factor that promotes one response may suppress the effect of the others. Thus, this multivariate optimization was applied for two bioanalytical methods for determination of TZD and metabolites, one by HPLC and other by CE, both using Hollow Fiber Liquid-Phase Microextraction (HF-LPME). The results establish the optimal values and elucidate how the factors that affect HF-LPME procedure perform in extraction efficiency for TZDs. Additionally, this study demonstrates that DF can be an important tool to optimize microextraction procedures.
  • Polystyrene-b-poly (acrylic acid) nanovesicles coated by modified chitosans for encapsulation of minoxidil Article

    Hanck-Silva, Gilmar; Minatti, Edson

    Resumo em Inglês:

    Abstract In this work, polystyrene-b-poly (acrylic acid) (PS-b-PAA) nanovesicles were coated by modified chitosans aiming at studying its physicochemical parameters. The chitosan (CS) was chemically modified to add hydrophilic and/or hydrophobic groups, obtaining three modified chitosans. The PS-b-PAA nanovesicles were obtained by organic (1,4-dioxane) cosolvent method in water, resulting in nanovesicles with less than 150 nm of diameter (polydispersibility index - PDI at 90° = 0.106), measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and negative zeta potential (-37.5 ± 3.2 mV), allowing the coating of its surface with oppositely charged polysaccharides, such as the CS and the modified chitosans. The coating process was made by mixing the colloidal suspensions with the CS and the modified chitosans at specific ENT#091;CS-xENT#093;/ENT#091;PS-b-PAAENT#093; ratios (0.001 to 1.0 wt %) and measuring the change in size and surface charge by DLS and zeta potential. Upon reaching maximum adsorption, the zeta potential parameter was positively stabilized (+26.7 ± 4.1 mV) with a hydrodynamic diameter slightly longer (< 200 nm of diameter). The encapsulation efficiency (EE) of minoxidil, quantified by capillary electrophoresis, was 50.7%, confirming their potential as drug delivery carriers and the coating process showed the possibility of controlling the surface charge nature of these nanovesicles.
  • Small cell lung cancer: an overview of the targets Article

    Valadares, Bruna Nardy; Stephano, Marco Antonio

    Resumo em Inglês:

    Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.
  • Chemical composition and biological activity of Baccharis erioclada DC. essential oil Article

    Bobek, Vanessa Barbosa; Cruz, Luiza Stolz; Oliveira, Camila Freitas de; Betim, Fernando Cesar Martins; Swiech, Juliane Nadal Dias; Folquitto, Daniela Gaspardo; Ito, Carmen Antonia Sanches; Budel, Jane Manfron; Zanin, Sandra Maria Warumby; Paula, Josiane de Fátima Padilha de; Miguel, Obdúlio Gomes

    Resumo em Inglês:

    Abstract The chemically complex essential oils of Baccharis species are associated with several biological activities, such as antimicrobial and antiulcerous properties. However, few studies have investigated Baccharis erioclada DC. Therefore, in this study, we aimed to characterize the essential oil of B. erioclada and evaluate its antioxidant, antimicrobial, and hemolytic potential. The essential oil was extracted by hydrodistillation using a Clevenger apparatus and analyzed via gas chromatography-mass spectrometry (GC-MS). Phosphomolybdenum complex formation, reducing antioxidant power, and thiobarbituric acid reactive substances (TBARS) methods were used to determine antioxidant potential. To evaluate the essential oil’s antimicrobial activity, minimum inhibitory concentrations (MIC) in Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were calculated. Hemolytic activity was determined in sheep red blood cells. Thirty-one compounds were identified via GC-MS analysis, representing 81.60% of the total essential oil. These compounds included: turmerone (27.97%), fokienol (13.47%), ledol (9.78%), and santalol (5.35%). The class of compounds identified was the oxygenated sesquiterpenes (62.52%). Antioxidant activity was confirmed via phosphomolybdenum complex formation and TBARS methods. Moderate antimicrobial activity and low hemolysis rates were displayed at concentrations of 250 and 500 μg/mL.
  • Ganoderma applanatum extract mediated synthesis of silver nanoparticles Article

    Dandapat, Sukumar; Kumar, Manoj; Ranjan, Rakesh; Sinha, Manoranjan Prasad

    Resumo em Inglês:

    Abstract Nanotechnology has been used in the field of medicine and pharmacology for its greater efficacy of drug delivery than crude molecules of drugs. In the present study medicinal mushroom Ganoderma applanatum extract mediated silver nanoparticles (AgNPs) were synthesized, characterized by Ultraviolet-visible (UV-Vis.) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction, Dynamic light scattering (DLS) and Furior transform-infrared (FTIR) spectroscopy. Maximum absorbance was recorded at 435nm by UV-Vis. The synthesized nanoparticles of 13.54nm-255nm in size with an average particle size of 58.77nm were analyzed by DLS. FTIR-Spectroscopy provided high transmission at 3606cm-1 corresponds for phenolic capping biochemical. Thus G. applanatum extract can be used for synthesis of silver nanoparticles and the synthesized nanoparticles may be used for development of future therapeutic agent for treatment of diseases.
  • Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo Article

    Dysarz, Leticia Pereira; Tavares, Melanie; Viçosa, Alessandra Lifsitch; Ribeiro, Mara Fernandes; Teixeira, Rafaela Gomes de Silva; Elias, Sabrina Calil; Silva, Márcio Robert Mattos da; Santos, Elisabete Pereira dos; Ricci-Júnior, Eduardo

    Resumo em Inglês:

    Abstract The aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation.
  • The chemical composition and antibacterial activity of a methanolic extract of Satureja khuzistanica Article

    Davoodi, Mansooreh; Nejad-Ebrahimi, Samad; Rustaiyan, Abdolhossein; Esmaeili, Davoud

    Resumo em Inglês:

    Abstract In the present study, the metabolite profiling of methanolic extract from aerial parts of Satureja khuzistanica Jamzad, as an endemic medicinal plant from Iran, was evaluated using HPLC-PDA-ESI. Then, the main compound from the extract was isolated and purified by using extensive chromatographic techniques. In addition, the structure of the isolated compounds was elucidated using 1D, 2D NMR, and MS spectrometry, upon which 22 compounds were identified. The antibacterial activity of diosmetin 7-rutinoside (6) and linarin (13) in combination with carvacrol as a major compound of the essential oil was tested against Pseudomonas aeruginosa and Staphylococcus aureus through disc diffusion and minimum inhibitory concentration methods. The results indicated that the linarin, when mixed with carvacrol as the main compounds in the essential oil of the plant, has a satisfactory activity against both Pseudomonas aeruginosa and Staphylococcus aureus with MIC values of 0.16 and 0.18 µg/mL, respectively. Further, the fractional inhibitory concentration (FIC) index indicated that this compound had synergism with carvacrol.
  • Artichoke extracts with potential application in chemoprevention and inflammatory processes Article

    Rotondo, Rosana; Cruz, Pablo Santa; Masin, Marianela; Bürgi, Milagros; Girardini, Javier; García, Stella M.; Rodríguez, Gustavo R.; Furlan, Ricardo L. E.; Escalante, Andrea M.

    Resumo em Inglês:

    Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.
  • The benefit of Silybum marianum in ethanol-induced reprotoxicity of male Wistar rat Article

    Talbi, Amina; Khelili, Kamel; Remita, Feriel; Abdennour, Cherif

    Resumo em Inglês:

    Abstract This study investigates the toxic effects of ethanol (Eth) on the reproductive system of male rats and the possible protective role of Silybum marianum seeds-infused solution (SMI) over six consecutive weeks of administration. Animals were divided into the following groups: control, SMI positive control (200 mg/kg/day), Eth1 (1 g/kg/day), Eth2 (2 g/kg/day), Eth1+SMI, and Eth2+SMI. Plasma testosterone concentration, epididymal spermatozoa biology, and testicular and epididymal MDA, GSH and GPx levels were evaluated. The results indicated a significant decrease in testis and epididymis weight, testosterone level, sperm concentration, sperm vitality and sperm motility (total motility, progressive motility, curvilinear velocity, straight-line velocity, velocity average path, beat cross frequency, and lateral head displacement) in both Eth1 and Eth2 compared to the control groups and the combined-treatment groups (Eth1+SMI and Eth2+SMI). Furthermore, results showed a significant elevation in MDA concentration with a significant decrease of testicular and epididymal GSH concentration and GPx activity in theEth1 and Eth2 groups compared to the combined-treatment groups. The administration of SMI succeeded in improving the parameters cited above in the combined-treatment groups compared to the Eth1 and Eth2 groups, and bring them to the levels seen in the control groups. To conclude, SMI has clearly protected reproductive indices against ethanol-induced reprotoxicity in male rats
  • Pulsatile Chronotherapeutic Drug Delivery for Controlling Early Morning Surge in Blood Pressure; Effect of Coating on Eplerenone In-vitro, In-vivo Release and Urinary Na/K Ratio Article

    Marzouk, Maha Abd El hameed; Darwish, Manal Kamal; Yassin, Ghada Ehab; El-Fattah, Marwa Adel Abd

    Resumo em Inglês:

    Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.
  • Vancomycin population pharmacokinetic modeling in children using Bayesian estimation and a Non Parametric Approach Article

    Silveira, Anna Luísa Oliveira; Alves, Geisa Cristina da Silva; Xie, Jiao; Roberts, Jason A; Sanches, Cristina

    Resumo em Inglês:

    Abstract To analyze microbiological effectiveness of vancomycin in children from a pediatric hospital through population pharmacokinetic modelling, as well as to propose dose adjustment, a cross- sectional study was performed in children under vancomycin treatment from the John Paul II Children’s Hospital, MG. In order to establish a model, concentrations versus time curves were analyzed using a population pharmacokinetic approach with Pmetrics®. Seventeen blood samples of 10 patients were collected. The best model to describe vancomycin population pharmacokinetic (PK) consisted of a two-compartment linear intravenous absorption model. The R² value and bias for population and individuals in observed versus predicted plot was 0.642 vs. 0.992 and the bias of 0.41 mg/L and 0.0778 mg/L, respectively. The covariables creatinine clearance, age, and body mass index were related to vancomycin PK. A relevant PK variability for vancomycin in pediatric patients was verified, which was significantly influenced by creatinine clearance, age, and body mass index. This result justifies the formulation of dosing recommendations for vancomycin in pediatric patients to achieve adequate pharmacodynamics targets.
  • Ethosomal gel: a novel choice for topical delivery of the antipsychotic drug Ziprasidone Hydrochloride Article

    Avasarala, Harani; Dinakaran, SathisKumar; Boddeda, Bhavani; Dasari, Sai Prasanna; Jayanthi, Vijaya Ratna; Swaroopa, Percy

    Resumo em Inglês:

    Abstract Oral delivery of antipsychotic drugs like Ziprasidone HCl has a disadvantage of gastric disturbance and lack of adherence to the treatment. In the present study, Ziprasidone HCl loaded ethosomal gel was formulated to avoid the disadvantages of oral delivery. The ethosomes were prepared using Lipoid S 75 with Isopropyl alcohol and Propylene glycol as the solvents. The formulated ethosomes were evaluated for different parameters like particle size, poly dispersibility index and entrapment efficiency. Based on diffusion studies, optimized ethosomal formulation was incorporated in carbopol 934 gel base. The final dosage form of ethosomal gel was evaluated for physical characteristics, drug content and proceeded with ex- vivo skin permeation studies. The maximum percentage of drug permeated after 24 hours was found to be 93.30±0.168. The flux was found to be 52.05± 0.564µg/hr/cm2. From the kinetic model fitting results, it was concluded that the ethosomal gel followed the first order kinetics and the higher “R2” values of the Korsmeyer Peppas model (R2=0.934, n=0.54) indicate that the encapsulating polymer is the responsible factor in controlling the release of the drug. The ethosomal gel loaded with ziprasidone HCl improves the bioavailability of ziprasidone HCl as well as surpassing drawbacks with oral delivery.
  • Seaweed Chara baltica: Isolation, Characterization and In vivo Antidiabetic Study Article

    Tatipamula, Vinay Bharadwaj

    Resumo em Inglês:

    Abstract For the first time, five known metabolites - 1 and 5 are reported from the ethyl acetate extract from seaweed Chara baltica (EAE). Both the metabolites and EAE were screened against free- radicals, α-glucosidase enzyme and glycaemia in albino rats. 4, 5 and EAE depicted significant antiradical and α-glucosidase inhibitory profile. Particularly, compound 5 showed equivalent inhibition of superoxide free radical as that of the standard drug with IC50 value of 32.0 µg/mL. In addition, the EAE (200 mg/kg b.w) revealed significant reduction in plasma glucose, body weight, total cholesterol, total glycerides and LDL levels in Streptozotocin-induced diabetic rats. The HDL levels were markedly augmented in EAE treated diabetic rats, when compared with control group. EAE abolished the increased lipid peroxidation content in both liver and kidneys. The histopathological examination of pancreas of EAE protected the Langerhans islets with the number of islet cells were found statistically significant, when compared to diabetic control pancreas. This is the first in vitro and in vivo antidiabetic report on C. baltica.
  • Efficacy of Lagopsis supina to promote blood circulation, remove blood stasis, and block inflammation in a rat model of traumatic blood stasis Article

    Xu, Tingting; Wang, Xiumei; He, Zhongwei; Yang, Li; Wei, Rongrui; Zhong, Guoyue; He, Junwei

    Resumo em Inglês:

    Abstract Lagopsis supina (Steph) IK. Gal. was a traditional Chinese medicinal plant for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuresis with little scientific validation. The aims of this study were first to evaluate the PBCRBS and anti-inflammatory effects of L. supina in a rat model of traumatic blood stasis (TBS). We demonstrated that an ethanolic extract of L. supina (LS, 460 mg/kg/d) possessed significant PBCRBS and remarkable inhibitory effect on inflammation cytokines, which were associated with renovated amount of the injured muscle fibers, alleviate the degree of the damaged tissue edema, decreased the number of inflammatory cells, increased the number of the capillary hyperplasia by hematoxylin and eosin (HE), as well as remarkably down-regulated ( p < 0.05 or p < 0.01) the levels of inflammation cytokines, including TNF-α, IL-6, IL-8, and IL-10 by ELISA. This finding provide a pharmacological basis and partial interpretation for the clinical application of L. supina, which has therapeutic properties for blood stasis syndrome (BSS) and inflammation-related diseases.
  • Exploring the role of cAMP in gabapentin- mediated pain attenuating effects in chronic constriction injury model in rats Article

    Sharma, Deepankshi; Jaggi, Amteshwar Singh; Arora, Kiran; Bali, Anjana

    Resumo em Inglês:

    Abstract It has been shown that an increase in cAMP leads to pain sensitization and gabapentin is shown to decrease cAMP levels. However, the impact of drugs modulating cAMP levels on analgesic actions of gabapentin is not studied. The present study investigates the effect of milrinone on pain attenuating effects of gabapentin in chronic constriction injury (CCI). Neuropathic pain was induced by putting four loose ligatures around the sciatic nerve. The pain assessment was done by noting the paw withdrawal threshold in the pinprick test, paw withdrawal latency in hot plate test and paw withdrawal duration in acetone drop test before surgery and on 14th- day post-surgery. There was a significant development of cold allodynia, mechanical and heat hyperalgesia on 14th day in CCI rats. Gabapentin (100 mg/kg) treatment for 14 days significantly attenuated pain, while milrinone (50 mg/kg) treatment for 14 days significantly exacerbated neuropathic pain in CCI-subjected rats. Milrinone (30 and 50 mg/kg) also attenuated analgesic actions of gabapentin in CCI-subjected rats, suggests that gabapentin may abolish neuropathic pain by increasing the intracellular levels of cAMP in CCI-subjected rats.
  • Serum from morbidly obese patients affects melanoma cell behavior in vitro Article

    Mocellin, Débora; Bratti, Letícia de Oliveira Souza; Silva, Adny Henrique; Assunção, Laura Sartori; Kretzer, Iara Fabricia; Filippin-Monteiro, Fabíola Branco

    Resumo em Inglês:

    Abstract Here we examined whether serum from obese patients could create a growth-enhancing microenvironment that alters gene expression in BRAF- and NRAS-mutated melanoma cell lines. SK-Mel-28 (BRAF-mutated) and Sk-Mel-147 (NRAS-mutated) cells were treated with pooled serum from 10 severely obese patients (BMI > 40 kg/m2), pooled serum from 6 healthy lean individuals (BMI = 18.5-24.9 kg/m2), or recombinant TNF-α. We found that obese patient serum enhanced migration capacity and increased NRAS expression levels in both BRAF- and NRAS-mutated melanoma cells. Although TNF-α is the major obesity-related cytokine and TNF-α levels were found to be increased in the serum of obese individuals, this cytokine made only a modest contribution to the migration capacity of melanoma cells. These results indicate that other components present in the serum of severely obese patients may be responsible for enhancing the migration capacity of melanoma cells. As TNF-α alone did not seem to significantly affect tumor cell behavior, anti-tumor strategies aimed at blocking TNF-α should be considered with caution in future studies, particularly when in vitro models are used as screening platforms for antitumor activity.
  • The Pharmacy of the Specialized Component of Pharmaceutical Policy of the 9th Regional Health Department of the State of Paraná and the Treatment of Ankylosing Spondylitis Article

    Scolaro, Letycia Longhi; Cremoneze, Isabela Zara; Moura-Costa, Gislaine Franco de

    Resumo em Inglês:

    Abstract The objective of this study was to trace the profile of patients with Ankylosing Spondylitis treated at the Pharmacy of the 9th Regional Health Department of Paraná and evaluate the relationship between pharmacological treatment, quality of life and disease activity index of these patients. Data collection was performed through interviews, application of BASDAI index and the ASQoL questionnaire. Male patients presented better rates (ASQoL 7.78 ± 6.04, BASDAI 4.26 ± 2.40) than female patients (ASQoL 12.08 ± 4.74, BASDAI 6.25 ± 2.43; p <0.05). Retired patients had higher disease activity and lower quality of life (BASDAI 6.59 ± 1.53, ASQoL 14 ± 2.89) than those who still worked (BASDAI 4.59 ± 2.87, ASQoL 7.68 ± 5.74); p <0.05), and the quality of life of patients with comorbidity (ASQoL 11.60 ± 5.47) was lower when compared to those without comorbidity (ASQoL 6.83 ± 4.90, p <0.05). Patients who used immunobiological drugs had better results (ASQoL 9.07 ± 5.86, BASDAI 4.73 ± 2.55) than those who used other drugs (ASQoL 13.08 ± 3.7, BASDAI 6.88 ± 2.15, p <0.05), and patients who used adalimumab showed better rates (ASQoL 7.42 ± 4.81, BASDAI 4.26 ± 2.47; p <0.05) when compared to other pharmacological treatments. Male patients showed a better response when compared to the female counterparts. Patients using adalimumab had a better quality of life and disease activity index than patients using other pharmacological treatments.
  • Circulating microparticles and thrombin generation in patients with Chronic Lymphocytic Leukemia Article

    Evangelista, Fernanda Cristina Gontijo; Ferrão, Aline Lúcia Menezes; Duarte, Rita Carolina Figueiredo; Gomes, Lorena Caixeta; Alves, Luan Carlos Vieira; Campos, Fernanda Magalhães Freire; Braga, Tatiane Vieira; Santiago, Marie Gabriele; Araújo, Sergio Schusterschitz da Silva; Carvalho, Maria das Graças; Sabino, Adriano de Paula

    Resumo em Inglês:

    Abstract Chronic Lymphocytic Leukemia (CLL) has shown great biological heterogeneity, with a variable prognosis, and a short survival in some patients. In this light, the present study focused on the prognostic utility of circulating microparticles (MPs) and a Thrombin Generation (TG) Profile for thrombotic risk and disease progression in CLL patients. Circulating microparticles and TG were evaluated in 35 patients with CLL and 35 healthy individuals. For circulating microparticles, significant differences were observed among the following groups: MPs derived from endothelial cells (p = 0.002), B lymphocytes (p < 0.001), platelets (p = 0.003), and Tissue Factor MPs in monocytes (p < 0.001). In all cases, MP values were higher for the CLL group. When compared to the controls, CLL patients presented a decrease in TG, characterized by a reduced endogen thrombin potential (ETP) (p = 0.031). When the results were analyzed according to the Binet stage, as compared to the controls, the Binet B+C group also presented lower ETP values (p = 0.009). No significant differences were observed between the control and the Binet A groups or between the Binet A and the Binet B + C groups. Although hemostatic alterations may occur in patients with CLL, these parameters do not seem to be useful to indicate disease progression.
  • Medication possession ratio in postmenopausal osteoporotic patients: a cross sectional study Article

    Haider, Sajjad; Khaliq, Sheikh Abdul; Naqvi, Syed Baqir; Fatima, Anab

    Resumo em Inglês:

    Abstract Osteoporosis is a chronic disease of bone that increases risk of low-trauma fracture. Chronic treatment may lead to lower adherence with medication. The current study aims are to determine adherence rate of antiosteoporotic medication by Medication Possession Ratio. Data has been collected from outpatient settings registering cases of postmenopausal osteoporotic women taking medications for an average duration of one year in Karachi. These patients were classified in lower, middle, and affluent socioeconomic classes. Collected data were analyzed by the standardized formula of Medication Possession Ratio and SPSS. Average Medication Possession Ratio ≥80% achieved by Risedronate Brands in the middle class (80.28%±4.41), the affluent class (82.50%±5.09), Raloxifen Brands in affluent class (93.62%±1.57), Gonadotropics in the middle class (81.36%±6.02), affluent class (91.09%±2.05), Alendronate Brands in affluent class (85.42%±5.46). Average Medication Possession Ratio is <80% with all antiosteoporotic medication in the lower class, while the average Medication Possession Ratio of Calcium and Vitamin D is ≥80% in all groups except lower class. Adherence rate was significantly higher among Alendronate group compare to Risedronate (p=0.044). Medication Possession Ratio is greater than 80% among all classes of low-cost antiosteoporotic medications. In addition, patients on once weekly oral medications are more adherent and compliant compare to oral daily or intranasal medications.
  • The effect of woody endocarpium of walnut alcoholic extract on acetic acid-induced ulcerative colitis in rats Article

    Keshavarzi, Zakieh; Ashekar, Aleme; Vatanchian, Mehran; Abbaspour, Alireza; Bibak, Bahram; Behnamfar, Morteza; Barzegar, Saeid; Shakeri, Farzaneh

    Resumo em Inglês:

    Abstract Various pharmacological effects including anti-inflammatory and anti-oxidant properties were shown for woody endocarpium of walnut alcoholic extract (WEW). In the study, the effect of the WEW extract in acetic acid induced ulcerative colitis in rats was evaluated. Thiol, glutathione peroxidase (GPX), malondialdehyde (MDA), superoxide dismutase (SOD) and gastric acid levels and pathological changes in the colon were investigated in the control group (C), ulcerative colitis group (UC), UC groups treated with WEW extract (10, 20, and 50 mg/kg) and sulfasalazine. Levels of gastric acid, MDA and pathological scores in colon were increased but SOD, GPX and thiol levels were decreased in UC animals compared to those of the control group (p<0.001). Treatment with the highest concentration of extract significantly improved level of thiol and pathological scores compared to the UC group (p<0.05 to p<0.001). Treatment with the two higher concentrations of extract also significantly decreased acid level compared to the UC group (p<0.01 to p<0.001). There was significant improvement in MDA due to treatment with the all concentrations of the extract (p<0.001). Sulfasalazine treatment also significantly improved most parameters compared to the UC group but did not changed pathological scores (p<0.05 to p<0.001). These results indicated a possible preventive therapeutic effect for the WEW extract on UC.
  • Development and in vivo evaluation of lipid-based nanocarriers containing Jatropha isabellei dry extract from the dichloromethane fraction intended for oral treatment of arthritic diseases Article

    Fröhlich, Janaina Kieling; Meyer, Priscila Aguiar; Stein, Taciane; Tonussi, Carlos Rogério; Lemos-Senna, Elenara

    Resumo em Inglês:

    Abstract In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound.
  • Synthesis of New Thiazole Derivatives Bearing Thiazolidin-4(5H)-One Structure and Evaluation of Their Antimicrobial Activity Article

    Evren, Asaf Evrim; Yurttaş, Leyla; Gencer, Hülya Karaca

    Resumo em Inglês:

    Abstract The first report about antimicrobial resistance was published in the 1940s. And today, the antimicrobial resistance has become a worldwide problem. Because of this problem, there is a need to develop new drugs. That’s why we synthesized some novel thiazolidine-4-one derivatives and evaluated their antimicrobial activity. The final compounds were obtained by reacting 2-[(4,5-diphenylthiazol-2-yl)imino]thiazolidin-4-one with some aryl aldehydes. The synthesized compounds were investigated for their antimicrobial activity against four Candida species, five gram-negative and four gram-positive bacterial species. The lead compounds (4a- h) were obtained with a yield of at least 70%. All compounds showed antimicrobial activity. Compound 4f (MIC: 31.25 µg/ml) exhibited more efficacy than the other compounds against C. glabrata (ATCC 24433). Compound 4b (MIC: 62.5 µg/ml) was the most active compound against all bacterial species, particularly K. pneumoniae (NCTC 9633). Whereas, compound 4c (MIC: <31.25 µg/ml) was observed as the most active compound against E. coli (ATCC 25922). In general, all compounds (4a-4h) showed antimicrobial activity against all fungi and bacterial species. Compounds 4b (2,6-dichlorobenzylidene), 4c (2,6-dihydroxybenzylidene), 4f (1H-pyrrol-2- yl)methylene), 4g (4-triflouromethylbenzylidene) and 4h (2,3,4-trimethoxybenzylidene) were determined as the most active compounds.
  • Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia Article

    Braga, Tatiane Vieira; Evangelista, Fernanda Cristina Gontijo; Santiago, Marie Gabriele; Ferrão, Aline Lúcia Menezes; Almeida, Tamara Dauare de; Barbosa, Bárbara Lima da Fonseca; Araujo, Sergio Schusterschitz da Silva; Ribeiro, Glaciano Nogueira; Carvalho, Maria das Graças; Sabino, Adriano de Paula

    Resumo em Inglês:

    Abstract Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.
  • Characterization, Antioxidant and Antibacterial Potentials of Tamarindus indica L. Fruit Pulp Extract Loaded O/W Nanoemulsions Article

    Songkro, Sarunyoo; Isnaini, Nadia; Sungkharak, Supreedee; Tanmanee, Niwan; Maneenuan, Duangkhae; Kaewnopparat, Nattha

    Resumo em Inglês:

    Abstract The main purposes of the current study were to formulate o/w nanoemulsions as a carrier for Tamarindus indica (tamarind) fruit pulp extract and to study the antioxidant and antibacterial potentials of nanoemulsions containing tamarind extract, focusing on cosmetic/hygiene applications. The o/w nanoemulsions using a mixture of Tween 80 and Span 80 as an emulsifier (5%w/w) were prepared by a high pressure homogenization process. Two concentrations of sweet tamarind extract, 3.3 and 6.6%w/w, based on the bioactivity study, were incorporated into the blank nanoemulsions to produce loaded nanoemulsions, F1-3.3TE (3.3%) and F1- 6.6TE (6.6%). As compared with the unloaded nanoemulsion, both tamarind extract loaded nanoemulsions showed reduced pH and significantly increased viscosity. Overall, the loaded nanoemulsions had droplet sizes of approximately 130 nm, zeta potential around -38 mV and polydispersity index (PDI) values less than 0.2. The nanoemulsion F1-3.3TE had better stability (e.g. significantly greater % tartaric acid content and lesser PDI value) than the nanoemulsion F1-6.6TE did. The antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay revealed that the nanoemulsions F1-3.3TE and F1-6.6TE had scavenging activities of 81.66 ± 0.77% and 63.80 ± 0.79%, respectively. However, antioxidant activity of these two formulations decreased under stress conditions (heating-cooling cycles). Such incidence did not occur for their antibacterial properties investigated by agar well diffusion technique. The two formulations exhibited inhibition zones of approximately 24.0-27.7 mm against Staphylococcus aureus and Staphylococcus epidermidis, responsible for malodor of underarms. The results suggest the potential of using sweet tamarind pulp extract loaded nanoemulsions as hygiene products.
  • Development of diethylcarbamazine-loaded poly(caprolactone) nanoparticles for anti-inflammatory purpose: Preparation and characterization Article

    Marcelino, Henrique Rodrigues; Gabinio, Brennda Martins; Lima, Marine Nascimento de; Urtiga, Silvana Cartaxo da Costa; Rodrigues, Gabriel Barros; Dantas, Bruna Braga; Araújo, Demétrius Antônio Machado de; Peixoto, Christina Alves; Oliveira, Elquio Eleamen

    Resumo em Inglês:

    Abstract Diethylcarbamazine-loaded nanoparticles were previously evaluated for their anti-inflammatory activity. However, little is known regarding their physicochemical properties. Thus, the purpose of this study was to physiochemically characterize diethylcarbamazine-loaded poly(caprolactone) nanoparticles and evaluate their in vitro cytotoxicity. All formulations were prepared using the double-emulsion method. The average particle size was in the ranged between 298 and 364 nm and the polydispersity indexes were below 0.3. The zeta potential values were marginally negative, which may be related to drug loading, as higher loading led to an increase in the modulus of the zeta potential values. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) analysis did not reveal any chemical interactions between the chemicals used and the absence of drug in crystalline form on the nanoparticle surfaces. The in vitro drug release study revealed a concentration-dependent release from the nanoparticles into the medium. The in vitro cytotoxicity assay demonstrated the biocompatibility of the blank and loaded nanoparticles. Hence, all formulations presented good physicochemical and safety properties, corroborating the in vivo anti-inflammatory activity, previously reported by our group.
  • Purified novel and new diferuloyl glycerate related phenolic acid from Pandanus odoratissimus flowers shows antioxidant, invertase inhibition and control against diabetic foot ulcer (DFU) causing bacterial pathogens - An in vitro study to establish an effective regulation over type 2 diabetes mellitus Article

    Suvetha, Sivamani Palanisamy; Sathishkumar, Thiyagarajan; Kumaraesan, Kuppamuthu; Rapheal, Vinohar Stephen; Muthukumaran, Velayutham; Thirugnanam, Natarajan

    Resumo em Inglês:

    Abstract Chronic type 2 diabetes mellitus (T2DM) and its associated diseases are major concern among human population and also responsible for significant mortality rate. Hence, the present study aims to evaluate and correlate the invertase inhibition, antioxidant activity and control against DFU causing bacterial pathogens by Pandanus odoratissimus flowers. Two dimensional preparative thin layer chromatography (2D PTLC) was adopted to purify the phenolic acid component and LC-MS2 was done to predict the phenolic acid structures. Standard spectrophotometry methods were adopted to investigate the in vitro invertase inhibitory and antioxidant (CUPRAC and ABTS) activities. Agar well diffusion and broth dilution assays were used to record the antibacterial property against DFU causing pathogens isolated from clinical samples. Statistical analyses were used to validate the experiments. A new and novel diferuloyl glycerate related phenolic acid (m/z 442) purified from PTLC eluate has recorded satisfactory cupric ion reducing power (ED50= 441.4±2.5 µg), moderate ABTS radical scavenging activity (IC50= 450.3±10 µg; 32.5±1.5%), and a near moderate, in vitro, invertase mixed type inhibition (24.5±4.5%; Ki: 400 µg). Similarly, bacterial growth inhibitory kinetics has showed a significant inhibition against E. coli and S. aureus.
  • Antioxidant activity of Haloxylon scoparium alkaloid extracts from Figuig region (southeastern of Morocco) Article

    Haida, Sara; Kribii, Abdelaziz; Daoud, Naima Ait; Belakhmima, Rida Allah; Kribii, Abderahim

    Resumo em Inglês:

    Abstract The aim of this paper is to study the chemical composition of alkaloids present in Haloxylon scoparium Pomel extracts and to evaluate their antioxidant capacity. The alkaloids were isolated from two parts of Haloxylon scoparium plant by two extraction protocols. and The quantitative study made it possible to propose the best protocol for the extraction of the alkaloids. Moreover, GC-MS analysis of alkaloid extracts allowed us to determine their chemical composition. Haloxylon scoparium contains four types of alkaloids: tetraisoquinolines, phenylethylamines, tryptolines and tryptamines. The main compounds are the tetraisoquinolines type, the predominant product of which was N-methylsalsoline. These compounds present a great interest for the researchers due to their various pharmacological and biological activities. The antioxidant effect of the different plant extracts was studied by two methods: the ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl hydrazyl free radical (DPPH·) scavenging tests. The results show that extracts of root part are more active than those from aerial part; the acetone/water extract is the most powerful. The interesting results obtained in this study will be supplemented by other analyses and biological tests in order to better valorize this plant.
  • Pharmaceutical Care Practice and Consequences on Quality of Life and Satisfaction of Diabetic Patients: A Randomized Clinical Trial Article

    Paulo, Patrícia Trindade Costa; Medeiros, Palas Atenéia Dantas de; Azevedo, Paulo Roberto Medeiros de; Diniz, Rodrigo dos Santos; Egito, Eryvaldo Sócrates Tabosa do; Araújo, Ivonete Batista de

    Resumo em Inglês:

    Abstract The pursuit of quality of life, which has become marked in recent years, has translated into important population health benefits. This study assessed the quality of life of patients with type 2 diabetes (T2DM) who received pharmaceutical care, and their satisfaction with the service provided in community pharmacies. This single blind, randomized controlled clinical trial included 100 patients. The intervention group (N=47) received pharmaceutical care by a clinical pharmacist and the control group (N=42) received standard care. The Quality of Life Diabetes Questionnaire (DQOL) was used to measure all participants´ quality of life at study enrollment and six months later. Satisfaction of the participants in the intervention group was measured using a validated 14-items questionnaire. At the end of the study, participants in the intervention group had a statistically significant improvement in DQOL scores ( -0.62 x 1.57, p < 0.001) and were highly satisfied with the intervention (96% excellent satisfaction scores). Pharmaceutical care practice was associated with high satisfaction and increased quality of life scores in T2DM patients. These results underscore the important role of pharmacists to improve the health of diabetic patients.
  • Chemical and biological properties of nordihydroguaiaretic acid Article

    Macena, Julio César; Renzi, Daniele Fernanda; Grigoletto, Diana Fortkamp

    Resumo em Inglês:

    Abstract Nordihydroguaiaretic acid (NDGA) is a natural product obtained by the alkaline extraction of dried plants of Larrea tridentata species. Due to the biological properties presented, such as antioxidant, anti-inflammatory, antiviral and cytotoxic capacity, this compound is being increasingly studied. In this review, it was evaluated the benefits of NDGA against different animal models. Besides that, it was found that this compound has antitumor activity similar to its synthetic derivative terameprocol in prostate tumors. The hypoglycemic effect may be evidenced by the inhibition of sugar uptake by NDGA; in obesity, studies have observed that NDGA presented a positive regulatory effect for Peroxisome proliferator-activated receptors (PPAR-α) involved in the oxidation of hepatic fatty acids and reduced the expression of lipogenic genes. Regarding its antioxidant potential, its mechanism is related to the ability to in vitro scavenging reactive substances. Although there are several studies demonstrating the benefits of using NDGA, there are also reports of its toxicity, mainly of liver damage and nephrotoxicity.
  • Post-marketing sampling and testing programs for licensed medicinal products: a narrative review Article

    Neves, Edvaldo Oliveira; Sales, Paloma Michelle de; Silveira, Dâmaris

    Resumo em Inglês:

    Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.
  • In vitro cytotoxicity assay of Fucoidan extracted from Turbinaria conoides against cancer cell lines MCF7, A549, and normal cell line L929 Article

    Santhanam, Revathi Chitra; Yacoob, Syed Ali Mohammed; Venkatraman, Anuradha

    Resumo em Inglês:

    Abstract The main aim of the study is to quantify the cytotoxic property of the Fucoidan extracted from the Turbinaria conoides using the MTT assay with the standard fucose. Fucoidan was extracted using the soaked water method and it was determined using the HPLC procedure the obtained Test sample Fucoidan extracted from the Turbinaria conoides and standard fucose was subjected to the cytotoxicity assay against the MCF7 Human breast cancer cell line, A549 lung cancer cell line, and L929 normal mouse fibroblast cell line. From the results it was found that the Test sample showed good IC50 value for MCF7 cell line then A549 with an increasing concentration 24 hours incubation at 37°C The IC50 for MCF7 was 115.21 µg/ml and A549 396.46µg/ml and the Fucoidan extract was checked for its cytotoxicity against the normal mouse fibroblast cell line L929, Fucoidan was found non-lethal to the L929 mouse fibroblast normal cell line. Standard fucose also gave a significant result towards MCF7 and against the L929. This indicates that the Fucoidan extracted from Tubinaria conoides shows better anticancer potential in it. Hence its application can be further extended in the pharmacological fields.
  • Evaluation of copaiba oil as enhancer of ibuprofen skin permeation Article

    Nogueira, Rodrigo José Lupatini; Grazul, Richard Michael; Silva Filho, Ademar Alves Da; Nascimento, Jorge Willian Leandro

    Resumo em Inglês:

    Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.
  • Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles Article

    BADAOUI, Fatima Zohra; BOUZID, Djallel

    Resumo em Inglês:

    Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.
  • Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats Article

    Braga, Andressa; Izolan, Jaqueline Schneider; Costa, Teresa Cristina Dalla; Araújo, Bibiana Verlindo de

    Resumo em Inglês:

    Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats.
  • Risk factors for potential drug-drug interactions of statins in patients with acute coronary syndrome Article

    Pejčić, Ana V.; Janković, Slobodan M.; Davidović, Goran

    Resumo em Inglês:

    Abstract The aim of our study was to assess risk factors for potential drug-drug interactions (pDDIs) of statins across different phases of treatment of acute coronary syndrome (ACS) patients: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase) and at discharge from hospital (third phase). This was a post hoc analysis of the data collected during the retrospective observational cohort study conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, Serbia. Patients prescribed statins were identified from the original study population: 156, 240 and 236 patients for the first, second and third phases, respectively. At least one statin pDDI was present in 113 (72.4%), 161 (67.1%) and 139 (58.9%) patients in the first, second and third phases, respectively. Heart failure, arrhythmias after ACS, CRP, triglycerides, length of hospitalization, number of prescribed drugs, antiarrhythmic drugs, and clopidogrel seem to increase the risk of statin pDDIs in at least one treatment phase. Physicians should be vigilant to the possibility of statin pDDIs in ACS patients who have factors that may increase their rate.
  • Dissolution test for oral suspension: an overview about use and importance Article

    Soares, Thaís dos Santos Paulino; Souza, Jacqueline de; Rosa, Lorena de Sousa; Marques-Marinho, Flávia Dias

    Resumo em Inglês:

    Abstract This work aims to ascertain the comprehensiveness of dissolution tests for oral suspensions registered in Brazil and the USA. After consulting literature since 1994, a paucity of information about dissolution methods for suspensions was detected. It makes it difficult to establish the most appropriate test parameters. In January, 2019, there were 46 drugs registered in Anvisa (Brazil) as oral suspension, being 47 reference, 173 generic and 114 interchangeable similar (IS) medicines; while in the USA, 90 drugs were registered as oral suspension by FDA, 235 Abreviatted New Drug Application and 111 New Drug Application medicines. Out of 46 and 90, only six and 15 drugs as oral suspension had a pharmacopeial dissolution test, corresponding to 70 (20.9%) and 82 (23.7%) products in Brazil and the USA, respectively. Dissolution studies were found for 17 drugs as oral suspension in the non-compendial literature. Dissolution test conditions were established to few marketable oral suspension drugs, most of which are BCS class II or IV. Thus, investing in dissolution studies could subsidize the registration of these products by regulators, especially for generic and IS drugs, by comparing dissolution profiles, and predicting their in vivo behavior to avoid exposure of healthy individuals to clinical research.
  • Mupirocin ointments: In vitro x In vivo bioequivalence evaluation Article

    Chagas, Stephanye Carolyne Christino; Pimenta, Camila de Almeida Perez; Kishishita, Juliana; Barbosa, Irla Carla França; Bedor, Danilo Cesar Galindo; Aquino, Katia Aparecida da Silva; Santana, Davi Pereira de; Leal, Leila Bastos

    Resumo em Inglês:

    Abstract Bioequivalence (BE) assessment of topical drug products is a long-standing challenge. Agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published several drafts in recent years suggesting different approaches as alternative to evaluate the BE. A proposed Topical Classification System (TCS) has even been discussed. Given the above, the objective of this research was to use in vitro and in vivo BE approaches to evaluate Brazilian marketed mupirocin (MPC) ointments, previously classified as TCS class The in vitro permeation test (IVPT) was performed by applying formulations to pig skin by Franz cells. The in vivo methodology was dermatopharmacokinetic (DPK). These approaches (in vivo tape stripping and IVPT) demonstrated capability of distinguishing among different formulations, thus making them useful methodologies for BE evaluation.
  • The study of the biological activities of Ziziphora clinopodioides Article

    Greta, Ulikhanyan; Hasmik, Galstyan; Karine, Dumanyan; Margarita, Beglaryan; Gayane, Poghosyan; Vladimir, Shekoyan; Hrachya, Ananikyan; Violeta, Ananikyan; Vigen, Goginyan; Ghukas, Ulikhanyan; Naira, Chichoyan; Sona, Taschyan

    Resumo em Inglês:

    Abstract The aim of the current study was to determine the chemical constituents of essential oil and to study the antibacterial and antioxidant activities of essential oil and the extracts obtained from the raw material of Ziziphora wild growing in the floras of Armenia and Artsakh cultivated in the hydroponic conditions. The essential oils were obtained by the method of hydro-distillation. The determination of the essential oil constituents were performed by the GC-MS method. Agar disk diffusion method was used to study the antimicrobial activity of essential oils. The antioxidant activity determination was carried out DPPH test by the spectrophotometric method, at the same time IC50 was determined. The highest values of the essential oils yield (1.25 ± 0.01%) and IC50 13.83±0.218(x10-5)g/l) were received for the plant cultivated in hydroponic conditions. For the first time in the above studied samples, by the method of GC-MS more than 70 components were revealed. The results of the study showed that essential oils of Ziziphora exhibit antimicrobial activity and the extracts revealed relatively expressed antioxidant activity. The study results show the future prospects of the use of Ziziphora not only as the source of flavonoids and essential oils, but also antimicrobial and antioxidant agents.
  • Calendula officinalis L. flower extract-mediated green synthesis of silver nanoparticles under LED light Article

    Santos, Angélica Panichi; Gonçalves, Melissa Marques; Justus, Barbara; Fardin, Daniele Priscila da Silva; Toledo, Ana Cristina Oltramari; Budel, Jane Manfron; Paula, Josiane Padilha de

    Resumo em Inglês:

    Abstract Silver nanoparticles (AgNPs) are among the most known nanomaterials being used for several purposes, including medical applications. In this study, Calendula officinalis L. flower extract and silver nitrate were used for green synthesis of silver nanoparticles under red, green and blue light-emitting diodes. AgNPs were characterized by Ultraviolet-Visible Spectrophotometry, Field Emission Scanning Electron Microscopy, Dynamic Light Scattering, Electrophoretic Mobility, Fourier Transform Infrared Spectroscopy and X-ray Diffraction. Isotropic and anisotropic silver nanoparticles were obtained, presenting hydrodinamic diameters ranging 90 - 180 nm, polydispersity (PdI > 0.2) and moderate stability (zeta potential values around - 20 mV).
  • Use of a mobile application for the control of anticoagulation with warfarin: a cluster randomized controlled clinical trial - Ijui/RS/Brazil Article

    Moraes, Rafael Manhabosco; Winkelmann, Eliane Roseli; Colet, Christiane de Fátima

    Resumo em Inglês:

    Abstract To evaluate the effectiveness of an anticoagulation protocol adapted in a mobile application (appG) for patients using warfarin. This was a cluster randomized controlled clinical trial carried out in basic health centers of Ijui, RS, Brazil, between April and October 2017. The appG was installed on the cell phones of all physicians belonging to the intervention group. Primary outcomes were bleeding and thrombosis, and secondary outcomes were changes in the dose of warfarin, use of new drugs, drug interactions, search for health services, and remaining on the target international normalized ratio. Thirty-three patients belonging to 11 basic health centers were included in this study. From these, 15 patients were in the intervention group which used the appG, and 18 were in the control group. After 6 months, patients in the appG group had fewer bleeding events (7% versus 50%, p-value=0.028) and a lower weekly dose of warfarin (29.3 ± 9.7 mg versus 41.7 ± 12.5 mg, p-value=0.030) when compared to the control group. The anticoagulation protocol adapted in a mobile app reduced bleeding in patients using warfarin.
  • The Relationship Between Neuroprotective Activity and Antigenotoxic and Acetylcholinesterase Inhibitory Effects of Glaucium corniculatum Extracts Article

    Kocanci, Fatma Gonca; Hamamcioglu, Buket; Aslim, Belma

    Resumo em Inglês:

    Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it’s protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.
  • Suppressive activity of RGX-365 on HMGB1-mediated septic responses Article

    Lee, Wonhwa; Kim, Ji-Eun; Yang, Sumin; Lee, Bong-Seon; Cho, Soo-Hyun; Lee, Jee-Hyun; Choi, Ga-Eun; Park, Eui Kyun; Song, Gyu-Yong; Bae, Jong-Sup

    Resumo em Inglês:

    Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.
  • Tadalafil and Sildenafil illicit association: Stability- indicating HPLC method, photodegradation kinetic and toxicological studies Article

    Pinto, Mayara Aramburú; Nicorena, Karine Favero; Machado, Michel Mansur; Oliveira, Luís Flávio Souza de; Paim, Clésio Soldateli; Silva, Fabiana Ernestina Barcellos da; Malesuik, Marcelo Donadel

    Resumo em Inglês:

    Abstract The illicit market of counterfeit medicines containing sildenafil and tadalafil has been causing serious public health problems. Thus, further studies on this illicit association are needed. A stability-indicating HPLC method was developed for simultaneous determination of tadalafil (TAD) and sildenafil (SIL) using a C18 column (250 x 4.6 mm, 5 µm). Detection was achieved at 284 nm, for TAD, and 292 nm, for SIL. The method was considered to be specific, linear, precise, accurate, robust, and sensitive. In the photodegradation kinetic studies, the drugs showed a first-order reaction rate when isolated, and zero-order when associated. Toxicological assays demonstrated that the photodegraded drugs decreased cell viability in compared to non- degraded drugs, suggesting cytotoxic activity. Additional, mutagenic activity was not observed under the tested conditions. Photodegraded drugs, in association, depicted DNA damage index, suggesting genotoxic effects. The obtained results will be able to support the forensic intelligence laboratories, as well as to alert the population about the risk inherent to consuming counterfeit products.
  • Current status of whitening agents and enzymes in Dentistry Article

    Pauli, Maria Cibelle; Kanemaru, Michel Yudi Shinkai; Francisco Vieira-Junior, Waldemir; Lima, Débora Alves Nunes Leite; Bicas, Juliano Lemos; Leonardi, Gislaine Ricci

    Resumo em Inglês:

    Abstract This study reviews the knowledge on the use of conventional dental whitening and the use of enzymes as a new approach in bleaching. A review of the literature was based on academic articles and on patents related to the use of enzymes in dental bleaching. Tooth whitening techniques used nowadays are well reported in the literature, and its mechanism of action consists of an oxidoreduction reaction with the release of free radicals. The great instability of radicals, when in contact with the tissues, promotes oxidation and reduction in the size of the pigment chains incorporated into them. These pigments are eventually broken down into smaller and smaller molecular chains and end up being diffused from the dental structure. In turn, the use of enzymes aimed at tooth whitening can be a less harmful alternative to the tooth because their specificity regarding the substrate makes them of great interest to perform specific reactions, reducing collateral effects. The use of proteolytic enzymes and oxidoreductases paired with the application of peroxides, can be a promising alternative for obtaining even better results in the dental bleaching process.
  • Gingko biloba extract improves the lipid profile, inflammatory markers, leptin level and the antioxidant status of T2DM patients poorly responding to metformin: A double- blind, randomized, placebo-controlled trial Article

    Hussain, Saad Abdulrahman; Aziz, Tavga Ahmed; Mahwi, Taha Othman; Ahmed, Zheen Aorahman

    Resumo em Inglês:

    Abstract The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as “add- on” therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin.
  • Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy Article

    Lim, Oon Zhi; Yeoh, Boon Seng; Omar, Norsuhana; Mohamed, Mahaneem; Zin, Anani Aila Mat; Ahmad, Rozaziana

    Resumo em Inglês:

    Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson’s Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.
  • Comparator product issues for biowaiver implementation: the case of Fluconazole Article

    Lazo, Raul Edison Luna; Teleginski, Lilian Klein; Maciel, Aline Biggi; Silva, Marcos Antônio Segatto; Mendes, Cassiana; Bernardi, Larissa Sakis; Murakami, Fábio Seigi; Sonvico, Fabio; Oliveira, Paulo Renato

    Resumo em Inglês:

    Abstract The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria.
  • Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism Article

    Dunjić, Momir; Krstić, Dejan; Živković, Jovan; Cvetković, Saša; Dunjić, Katarina; Mirković, Miloš; Ranković, Goran; Ranković, Branislava; Sokolović, Danka; Sokolović, Dušan

    Resumo em Inglês:

    Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.
  • Comparison between DAS28-ESR and DAS28- CRPus for patients with rheumatoid arthritis: application in a population of southern Brazil Article

    Berso, Juliane de Lara; Montes, Elisangela Gueiber; Vellosa, José Carlos Rebuglio; Mansani, Fabiana Postiglioni; Toledo Júnior, Alceu de Oliveira; Schafranski, Marcelo Derbli

    Resumo em Inglês:

    Abstract The Disease Activity Score 28 (DAS28) shows discrepancies when using erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) scores to assess rheumatoid arthritis (RA). This study aimed to verify the agreement between the DAS28-CRP and DAS28-ESR scores in patients with RA from the south of Brazil. A unicentric cross-sectional study was performed (n = 56). The diagnosis of the patients followed the American College of Rheumatology/ European League Against Rheumatism criteria, and their DAS28 were calculated. The DAS28- ESR score was higher than the DAS28-CRP (DAS28-ESR mean 4.8±1.6; DAS28-CRP mean 4.3±1.4) for 83.9% of the patients. The DAS28-CRP and DAS28-ESR scores showed a very strong correlation (Pearson’s coefficient = 0.922; P<0.0001, 95% CI +0.87 to +0.95, statistical power 100%). Spearman’s correlation coefficient (0.49; P=0.0001, 95% CI +0.25 to +0.67, statistical power 47.54%) showed a moderate correlation between the unique components of the DAS28 formulas. There was agreement between the tests in only 36 of the patients (64.29%). Among the discordant categories, DAS28-ESR overestimated the classification in 16 patients (28.5%). The Kappa coefficient between the categories was 0.465 (SE 0.084, 95% CI +0.301 to +0.630), showing a moderate degree of agreement between the instruments. Although the DAS28-ESR and DAS28-CRP were highly correlated, they differed significantly in terms of patient categorization and should not be used interchangeably.
  • Cord factor producer Mycobacterium abscessus subsp. bolletii in asymptomatic immunocompetent host sputa samples Article

    Freitas, Beatriz Cardoso de; Meneguello, Jean Eduardo; Eugenio, Livia Gisella Fernandes; Lemos, Rhayana; Scodro, Regiane Bertin de Lima; Siqueira, Vera Lucia Dias; Caleffi-Ferracioli, Katiany Rizzieri; Cardoso, Rosilene Fressatti

    Resumo em Inglês:

    Abstract We report a case of Mycobacterium abscessus subsp. bolletii colonization in upper respiratory tract of an immunocompetent patient, who was misdiagnosed as tuberculosis by Acid Fast Bacilli (AFB) and cord factor formation observed directly from the sputa culture in liquid medium. This fact reflected a significant impact on the individual case’s life and showed the importance to identify the mycobacteria isolated from clinical sample at species level, and to determine the true implication of nontuberculous mycobacteria (NTM) detected in clinical samples.
  • A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat Article

    Amini, Negin; Badavi, Mohammad; Goudarzi, Mehdi

    Resumo em Inglês:

    Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.
  • Cytotoxic evaluation and LC-MS/MS analysis of aerial parts of Eryngium kotschyi Boiss. grown in Turkey Article

    Arslan, Ayşe Kübra Karaboğa; Paşayeva, Leyla; Tugay, Osman

    Resumo em Inglês:

    Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 μg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds.
  • Interchangeability among carbamazepine formulations: the impact over epilepsy patients Article

    Frade, Virgínia Paula; Paiva, Maria José Nunes de; Martins, Isarita; Castro, Whocely Victor de; Belo, Vinícius Silva; Baldoni, André Oliveira; Lima, Priscila de Freitas; Sanches, Cristina

    Resumo em Inglês:

    Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the “Interchangeable Pharmaceutical Product in the Treatment of Epilepsies” questionnaire was applied. The questionnaires “Adverse Events Profile” and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event “problems with skin” incresead (p=0.023) and “upset stomach” decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: “energy/fatigue” (p=0.048) and “total score” (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients’ perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients’ life.
  • Role of ACE and ACE-2 in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart Article

    Kumar, Vimal; Goyal, Ahsas; Gupta, Jeetendra Kumar

    Resumo em Inglês:

    Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff’s apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.
  • Naringin is a promising natural compound for therapy of iron-overload disorders Article

    Jahanshahi, Mehrdad; Khalili, Masoumeh; Margdari, Asra; Aalikhani, Mahdi

    Resumo em Inglês:

    Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl’s staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders.
  • Development and validation of analytical methods by HPLC for quality control of avermectins and milbemycins in bulk samples Article

    Dutra, Flávia Viana Avelar; Teixeira, Leila Suleimara; Pires, Bruna Carneiro; Florez, Diego Hernando Ângulo; Teixeira, Roseane Andrade; Borges, Keyller Bastos

    Resumo em Inglês:

    Abstract This work aims to develop analytical methods using high-performance liquid chromatography with a diode array detector (HPLC-DAD) for analysis and quantification of avermectins (AVMs) and milbemycins (MBMs) in bulk samples. First, the methods were optimized and some parameters such as temperature, flow rate, injection volume and mobile phase with different proportions of solvents were evaluated. The best chromatographic conditions were obtained using the Phenomenex® C18 (150 × 4.60 mm, 5 μm) column at a temperature of 20 °C, flow rate of 1.2 mL min-1, injection volume of 20 μL, and detection at 250 nm. Acetonitrile: ultrapure water (87: 13, v/v) was used as mobile phase for moxidectin and eprinomectin, and acetonitrile: methanol: ultrapure water (53: 35: 12, v/v/v) for abamectin and ivermectin. Under these conditions satisfactory results were obtained, with appropriate limits of detection and quantification, acceptable linearity, precision, accuracy, and robustness. These methods satisfy the need for analytical methods for the multi-determination of MBMs and the B1a and B1b forms of AVMs by HPLC-DAD, which can be considered simple, effective, innovative and should aid in the development of the field.
  • Nanobubbles: A Novel Targeted Drug Delivery System Article

    Pasupathy, Rangasamy; Pandian, Pitchaimuthu; Selvamuthukumar, Subramanian

    Resumo em Inglês:

    Abstract Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.
  • Pharmaceutical care and evaluation of adherence to antiretroviral therapy in people living with HIV/AIDS Article

    Schoenherr, Marcio Rodrigo; Santos, Lucimary Afonso dos; Remor, Eduardo; Campanha, Angela Maria

    Resumo em Inglês:

    Abstract Highly Active Antiretroviral therapy (HAART) depends on optimal adherence to be effective. Pharmacotherapeutic follow-up can be used as a strategy for treatment fidelity. To provide pharmaceutical care for HAART patients, to assess adherence, to identify and resolve drug related problems (DRP). This is a prospective, interventional study aimed at people on HAART. Data was collected using the pharmacotherapeutic follow-up form and CEAT-VIH. There was a predominance of women (59%), older than 33 years (75%), mostly single (43%). Regarding adherence, 64% had insufficient adherence at the start of the study, while 36% had strict/adequate adherence. After the pharmacotherapeutic follow-up, 70% presented strict/adequate adherence. Regarding HAART, the relationship between adhesion versus time of HAART and adherence versus regimen used was significant, considering that less time of therapy and regimen containing protease inhibitors are predictors for insufficient adherence. Regarding the DRP identified (f=77), missed pills (32%), untreated disease, incorrect management frequency, and undue self-medication (12%) were the most frequent. Pharmaceutical interventions (f=137) were predominantly advising related to specific pharmacological treatment (32%), non-pharmacological measures (20%), and medication suspension (9%). Pharmaceutical care was shown to be animportant strategy, within the multi professional team, to improve adherence, besides identifying and resolving DRP.
  • Use of medication and associated factors in adults living in Rio Branco, Acre. Use of medication in adults Article

    Neves, Luana Christina Esteves das; Amaral, Thatiana Lameira Maciel; Amaral, Cledir de Araújo; Monteiro, Gina Torres Rego; Vasconcellos, Maurício Teixeira Leite de; Costa, Emmerson Corrêa Brasil da

    Resumo em Inglês:

    Abstract We analyzed use of medication and associated factors in adults aged 18-59 years living in Rio Branco, Acre. This is a cross-sectional and population-based study that used a probabilistic sample of the population from rural and urban areas of the city of Rio Branco, Acre. The Prevalence Ratio (PR) was calculated with 95% confidence intervals and associations were estimated by Poisson regression. This study found a 29.4% prevalence ratio of use of medication among individuals aged from 18 to 59 years (685 adults: 473 women and 212 men; producing estimates for 211,902 adults: 110,769 women and 101,133 men). After adjusted analysis, their use was associated with: age (50-59 years, PR: 2.36; 95%CI: 2.29-2.43); women (PR: 1.25; 95%CI: 1.23-1.27); up to elementary school (PR: 1.13; 95%CI: 1.11-1.15); and poor or very poor self-rated health (PR: 1.47; 95%CI: 1.43-1.51). The health conditions associated with use of medication were: number of comorbidities, hypertension, diabetes, insomnia, depression, number of health complaints and use of health services. The most frequently used drugs were those belonging to the following ATC categories: alimentary tract and metabolism, cardiovascular system, nervous system, and the musculoskeletal system.
  • Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes Article

    Şalva, Emine; Alan, Saadet; Karakoyun, Berna; Çakalağaoğlu, Fulya; Özbaş, Suna; Akbuğa, Jülide

    Resumo em Inglês:

    Abstract Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.
  • Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia Article

    Owjfard, Maryam; Bigdeli, Mohammad Reza; Safari, Anahid; Namavar, Mohammad Reza

    Resumo em Inglês:

    Abstract Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression.
  • Optimization of expression yield in a stable cell line expressing a novel mutated chimeric tissue plasminogen activator (mt-PA) Article

    Raigani, Mozhgan; Barkhordari, Farzaneh; Moazzami, Reza; Davami, Fatemeh; Mahboudi, Fereidoun

    Resumo em Inglês:

    Abstract The development of stable cell lines producing recombinant proteins is very time-consuming and laborious. One of the practical approaches successfully performed is Fluorescence-Activated Cell Sorting (FACS). A mutated chimeric tissue plasminogen activator (mt-PA) was developed by removing the first three domains of t-PA, insertion of GHRP sequence and mutation toward resistance to plasminogen activator inhibitor-1 (PAI-1). In the current study, a new stable CHO-DG44 cell line producing mt-PA was developed by two sequential clonal selections: FACS and clonal-selection by limiting dilution. Furthermore, the expression was more evaluated using two different expression media. Finally, the high-producing clones were selected based on the dot blot and amidolytic activity test. The transfection efficiency of CHO-DG44 cells was 38% as measured by flow cytometry on green fluorescent protein (GFP). After performing FACS on stable cell pools, the expression yield was increased to fifty-fold. In terms of growth profile, CD-DG44 showed higher viability and cell density results than ProCHO5 medium. The expression of mt-PA was significantly higher in CD-DG44 than in ProCHO5, 765 and 280 IU/mL, respectively. Our data indicated that selection of an appropriate expression medium played a critical role in the development of potent producing stable cells by FACS.
  • Quantitative Characterization of the Chemical Space Governed by Human Carbonic Anhydrases and selenium-containing derivatives of solfonamides Article

    Rasti, Behnam

    Resumo em Inglês:

    Abstract Due to the fact that different isoforms of carbonic anhydrase play distinct physiological roles, their diseases/disorders involvement are different as well. Involvement in major disorders such as glaucoma, epilepsy, Alzheimer’s disease, obesity and cancers, have turned carbonic anhydrase into a popular case study in the field of rational drug design. Since carbonic anhydrases are highly similar with regard to their structures, selective inhibition of different isoforms has been a significant challenge. By applying a proteochemometrics approach, herein the chemical interaction space governed by acyl selenoureido benzensulfonamides and human carbonic anhydrases is explored. To assess the validity, robustness and predictivity power of the proteochemometrics model, a diverse set of validation methods was used. The final model is shown to provide valuable structural information that can be considered for new selective inhibitors design. Using the supplied information and to show the applicability of the constructed model, new compounds were designed. Monitoring of selectivity ratios of new designs shows very promising results with regard to their selectivity for a specific isoform of carbonic anhydrase.
  • Innovation in Pharmaceutical Assistance Article

    Santos, Jean Leandro Dos

    Resumo em Inglês:

    Abstract Innovation is the driving force that is able to create and transform products, processes, and organization in the health system. Innovation in the field of pharmaceutical assistance covers a wide spectrum of aspects, from drug discovery to pharmaceutical care, contributing to the improvement in treatments through novel drugs or methods. This work will present the major characteristics of innovation with special emphasis on aspects pertaining to pharmaceutical assistance. The types and models of innovation, as well as the interaction between academia and industry, will be presented with examples of successful products and methods. In addition, the challenges and perspectives for innovation in pharmaceutical assistance will be discussed with a focus on drug discovery.
  • Optimization of glycerol-based medium composition for antifungal metabolites production by Bacillus subtilis Article

    Trivunović, Zorana; Zahović, Ida; Grahovac, Jovana; Jokić, Aleksandar; Dodić, Siniša; Mitrović, Ivana; Dodić, Jelena

    Resumo em Inglês:

    Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.
  • Psychoactive drugs in the Brazilian public health system: Use profile and associated factors Article

    Siani-Morello, Manuela Roque; Pereira, Lucas Borges; Ferreira, Iahel Manon de Lima; Aliste, Marcela Jirón; Pereira, Leonardo Régis Leira

    Resumo em Inglês:

    Abstract The purpose of this study is to estimate the prevalence of and characterize the use of psychoactive drugs among drug users in a Brazilian municipality, relating the findings to factors associated with the consumption of these substances. Through a cross-sectional design, 1,355 drug users from the public health systems community pharmacies were interviewed. Sociodemographic and health-related data were collected, as well as any other prescribed drugs. The prevalence of psychoactive drug use within the last month was 31.0%, with antidepressants and benzodiazepines being the most prescribed (53.5% and 24.6% respectively). Most psychoactive drug users were female (81.9%), lived with a partner (52.6%), had private health insurance (69.2%) and a monthly per-capita income up to one minimum wage (54.0%). The adjusted Odds Ratio (OR) confirmed the following factors to be positively associated with the use of psychoactive drugs: female gender (OR=2.06; 95% CI 1.44; 2.95), age ≥60 years old (OR=1.77; 95% CI 1.26; 2.48), follow-up with a psychologist (OR=4.12; 95% CI 1.84; 5.25), absence of regular physical activity (OR=1.59; 95% CI 1.13; 2.23), and smokers (OR=1.94; 95% CI 1.26; 2.97). Approximately one out of three individuals used at least one psychoactive drug. Health managers should focus the planning and actions aimed at their rational use for these groups, leading to increased overall treatment success.
  • Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract Article

    Kolisnyk, Tetiana; Vashchenko, Olga; Ruban, Olena; Fil, Nataliya; Slipchenko, Galina

    Resumo em Inglês:

    Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.
  • Differential Regulation of Integrin α5 and β4 in Normal and Psoriatic Epidermal Keratinocytes Article

    Zhou, Jiong; Shen, Ji-Yang; Man, Xiao-Yong; Li, Wei; Chen, Jia-Qi; Cai, Sui-Qing; Zheng, Min

    Resumo em Inglês:

    Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and β4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and β4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and β4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes’ α5 and β4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes’ α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed β4. Psoriatic keratinocytes’ α5 was increased by IL-13/17A, decreased by IFN-γ; but β4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and β4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently.
  • Use of biorelevant dissolution media in dissolution tests as a predictive method of oral bioavailability Article

    Lemos, Hemilliano de; Prado, Livia Deris; Rocha, Helvécio Vinícius Antunes

    Resumo em Inglês:

    Abstract Dissolution is a key step in the uptake of oral drugs. In order to compare the behaviour of the dissolution of two formulations, the dissolution profile test was used. This assay must be discriminative and should mimic in vivo conditions. Many dissolution media described in pharmacopoeias are not predictive of bioavailability. Due to this, biorelevant media are used as an alternative to solve this problem. The objective of this work is to evaluate the relevance of biorelevant dissolution media to predict in vivo drug dissolution. For this, a bibliographic search was carried out in scientific databases. The search was first performed for articles verifying the physicochemical properties of human gastrointestinal fluids. Subsequently, a comparison was made between the properties of gastrointestinal fluids and those of biorelevant and pharmacopoeial media. Finally, the results of bioequivalence studies and dissolution profile tests in biorelevant media described in the literature were compared. The results revealed that there are a few publications that have analysed some physicochemical properties of gastrointestinal fluids. In addition, high variability was observed for some properties. Regarding the comparison of these properties with pharmacopoeial media and biorelevant media, the analysis showed that the biorelevant media are more similar to gastrointestinal fluids than the pharmacopoeial media. Finally, the in vitro dissolution profile results were similar to the results obtained in vivo. Thus, biorelevant media may be useful for analysing dissolution profiles.
  • Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach Article

    Joshi, Manjusha; Gokhale, Chinmay; Kenjale, Prathmesh; Pokharkar, Varsha

    Resumo em Inglês:

    Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.
  • Protective effects of Baicalin injection on severe acute pancreatitis through regulating follistatin-like-1 signaling pathway by down-regulating miR-429 expression in mice Article

    Li, Hui; Yang, Wei; Liu, Ming-wei; Wan, Lin-jun; Wang, Yan-qiong

    Resumo em Inglês:

    Abstract In China, Scutellaria is used for treating inflammatory-related diseases. Baicalin is the main active component of Scutellaria and has protective effects on acute pancreatitis. However, the mechanism of Baicalin is still unclear. In this study, the protective effects of baicalin on acute pancreatitis induced by taurocholate and its mechanism are investigated. In this study, mice were randomly divided into three groups: sham operation, model, and treatment groups. Acute pancreatitis in mice was induced by intraperitoneal injection of taurocholate (35 mg/kg). The treatment group was given baicalin (100 mg/kg) 2 h before acute pancreatitis induction. The mRNA expression levels of miR-429, nuclear factor kappa B65(NF-kB65), toll-like receptor 4(TLR4), TNF receptor associated factor6 (TRAF6), NF-kappa-B inhibitor(IkB), Follistatin-like 1 (FSTL1), and interleukin-1 receptor-associated kinase (IRAK) in the liver tissues 24 h after intraperitoneal injection were detected by RT-PCR. Then, the expression levels of NF-kB65, p-NF-κB65, TLR4, TRAF6, IkB, FSTL1, IRAK, p- IRAK, and p- IkB-а proteins were detected by Western blot. IL-6, TNF-α and IL-1 β in plasma were measured by ELISA, and histopathological changes in the pancreases of the mice were observed. The results showed that after baicalin treatment, miR-429 expression in the pancreatic tissues and the expression levels of NF-kB65, TLR4, TRAF6, p-IkB-а, FSTL1, and p-IRAK decreased. Similarly, pancreatic myeloperoxidase (MPO) activity and the plasma levels of IL-6, TNF-а, IL-12, IL-1β1, endotoxin, serum amylase, and lipase were reduced. Thus, the pancreatic injury induced by taurocholate was alleviated. The present study indicates that pretreatment with Baicalin can alleviate acute pancreatic injury induced by taurocholate in mice. The mechanism may be associated with the decreased miR-429 expression, reduced FSTL1 signaling pathway activity, TLR4 and TLR4/MyD88 signaling pathway inhibition, and reduced pancreatic inflammation. FSTL1 is the regulatory target for miR-429.
  • Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease: A randomized clinical trial Article

    Zojaji, Seyyed Abbas; Mozaffari, Hooman Mosannen; Ghaderi, Pouya; Zojaji, Faegheh; Hadjzadeh, Mousa-Al-Reza; Seyfimoqadam, Monireh; Ghorbani, Ahmad

    Resumo em Inglês:

    Abstract Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of Anethum graveolens, Citrus aurantium, Cynara scolymus, Portulaca oleracea, and Silybum marianum (2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD.
  • Effects of thymoquinone in a rat model of reserpine-induced depression Article

    Kuzay, Dilek; Dileköz, Ergin; Özer, Çiğdem

    Resumo em Inglês:

    Abstract The objective of this study is to examine the antidepressant and antioxidant effects of thymoquinone (TQ) on reserpine-induced depression, and to investigate the antidepressant and antioxidant activity of combined treatment of TQ+citalopram. In total, 36 male Wistar rats were randomly divided into 6 groups: 1)control1, 2)control2, 3)reserpine, 4)reserpine+TQ 5)reserpine+citalopram and 6)reserpine+TQ+citalopram. Depression was induced by administering intraperitoneal reserpine of 0.2mg/kg/14days. For antidepressant effects, 10 mg/kg TQ and/or 10 mg/kg citalopram was administered intragastrically 30 minutes prior to the administration of reserpine. Rat behavior was examined using the Behavioral Test following the completion of treatment protocol. Total nitric oxide (NOx) levels, malondialdehyde (MDA) levels, total oxidants status (TOS), total antioxidant status (TAS) in brain cortex, plasma as well as brain cortex glutathione (GSH) and levels of plasma total sulfhydryl groups (RSH) were examined. Treatment with TQ ameliorated the reserpine-induced changes in the Behavioral Test (p<0.05). TQ treatment significantly increased dopamine (DA) and noradrenaline (NA) expressions when compared to the R group (p<0.01). Serotonin (5-HT) expression also increased significantly (p<0.05). Brain cortex and plasma TOS, MDA and NOx levels decreased, whereas TAS, GSH and RSH levels increased (p< 0.05). TQ has the ability to prevent depression induced by reserpine. The combination of TQ+citalopram can be used in the treatment of depression with a stronger antioxidant effect
  • Research on Molecular Mechanism of Fructus Ligustri Lucidi against Osteoporosis based on Network Pharmacology Article

    Li, Yanling; Zhang, Dongdong; Lv, Mingti; Ye, Tongsheng

    Resumo em Inglês:

    Abstract TCMSP platform of systematic pharmacology of traditional Chinese medicine This study aimed to investigate the molecular mechanism of Fructus Ligustri Lucidi (NZZ, Chinese abbreviation) against osteoporosis (OP) by means of network pharmacology.ChemDraw Professional 15.1 software and Molinspiration Smiles database were used to draw the chemical formulas of the components. The active ingredients and related target proteins of NZZ were searched in platform of systematic pharmacology of traditional Chinese medicine database, Drugbank, Therapeutic Target Database, SymMap and other databases. Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the selected target through Enrichr and KEGG Automatic Annotation databases, and their mechanism was studied. A total of 29 compounds and 140 corresponding targets, including 14 key targets and 14 protein factors in protein-protein interaction core network were obtained. The key targets were tumor necrosis factor(TNF), interleukin(IL)-6R and sestrogen receptor alpha. The number of GO items was 466 (P<0.05), including 399 items of biological process (BP), 54 items of cell composition (MF) and 13 items of molecular function (CC). KEGG pathway enrichment screened 85 signaling pathways (P<0.05), including the IL-17 signaling pathway, TNF signaling pathway, advanced glycation end products and their receptors signaling pathway and cAMP signaling pathway. The active ingredients of NZZ. exert their anti-OP effects through multi-components, multi-targets and multi-pathways, which can provide new evidence for further study of their anti-OP mechanism.
  • Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies Article

    Damgalı, Şükran; Özdemir, Samet; Kaya, Gizem; Demirkoz, Aslı Barla; Üner, Melike

    Resumo em Inglês:

    Abstract To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière’s disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated.
  • Synergistic interaction of fluconazole/sodium bicarbonate on the inhibition of Candida glabrata phospholipase gene Article

    Hosseini, Seyed Mohammad Karim; Alizadeh, Fahimeh; Nouripour-Sisakht, Sadegh; Khodavandi, Alireza

    Resumo em Inglês:

    Abstract Candida glabrata infections are responsible for deaths of people globally. Fluconazole is known to be less effective against C. glabrata, which developed many strategies to evade being destroyed by fluconazole. To achieve enhanced efficacy of fluconazole against C. glabrata, the interaction of fluconazole with sodium bicarbonate was investigated using the CLSI guidelines. The efficacy of fluconazole alone and in combination with sodium bicarbonate was evaluated using the time-kill and phospholipase production assays. Eventually, the expression of PLB was assessed using semi-quantitative RT-PCR to investigate the inhibitory properties of fluconazole alone and in combination with sodium bicarbonate against C. glabrata. The fluconazole/sodium bicarbonate combination displayed synergistic and antagonistic effects (FICI= 0.375-4.25). In C. glabrata ATCC, SN 152, and SN 164, the fluconazole/sodium bicarbonate combination exhibited a significant fungicidal activity (p< 0.05) but antagonistic effect in the case of SN 283. With exception of SN 283, a significant reduction was noted in phospholipase production in clinical isolates of C. glabrata treated with fluconazole/sodium bicarbonate combination. The PLB was down-regulated significantly by 0.168-0.515 fold in C. glabrata treated with fluconazole/sodium bicarbonate. The results suggested fluconazole/sodium bicarbonate to have a potential synergistic interaction in C. glabrata, and the underlying mechanism may be associated with phospholipase gene.
  • Antioxidant and antimicrobial properties of dihydroquercetin esters Article

    An, Hyun-Jin; Yoon, Young-Kyung; Lee, Jae-Duk; Jeong, Noh-Hee

    Resumo em Inglês:

    Abstract Flavonoids display various beneficial biological properties, such as antioxidant activity and low cytotoxicity, which make them useful ingredients in foods, pharmaceuticals, and functional cosmetics. In particular, dihydroquercetin (DHQ) is found in various forms, and its derivatives exhibit interesting biological properties. Herein, we report the synthesis of acetylated and butyrylated dihydroquercetin derivatives and their antimicrobial and antioxidant properties. The DHQ derivatives were identified using 1H and 13C NMR spectroscopies and high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. The chemical stabilities of the acetylated dihydroquercetin derivatives were found to depend on the number of acetate groups, with 3,3',4',4,7-pentaacetyldihydroquercetin found to be the most stable acetylated dihydroquercetin. Furthermore, 7,3',4'-triacetyl- dihydroquercetin exhibited potent antioxidant activity, with an IC50 of 56.67 ± 4.79 μg/mL in the 1,1-diphenyl-2-picrylhydrazyl assay, with DHQ exhibiting a value of 32.41 ± 3.35 μg/mL. The reactive-oxygen-species-scavenging activity of 7,3',4'-triacetyldihydroquercetin was highest among the esters in the ferric reducing ability of plasma assay, but lower than that of DHQ. Overall, both DHQ and 7,3',4'-triacetyldihydroquercetin exhibited antimicrobial behavior against S. aureus and P. acnes using the paper disc assay. DHQ displayed a higher antimicrobial activity, with minimum inhibitory concentrations of 625 μg/mL (P. acnes), 2,500 μg/mL (S. aureus), and 5,000 μg/mL (E. coli). DHQ and acetylated dihydroquercetins are potentially useful as complex antioxidant and antimicrobial materials.
  • Global endothelial function assessment using pulse wave analysis in hypercholesterolemia Article

    Ibrahim, Nik Nor Izah Nik; Rahman, Razlina Abdul; Azlan, Maryam; Rasool, Aida Hanum Ghulam

    Resumo em Inglês:

    Abstract To compare global endothelial function assessed by pulse wave analysis (PWA) using the ratio of endothelium dependent vasodilatation (EDV) to endothelium independent vasodilatation (EIV) in patients with hypercholesterolemia and controls. 92 subjects [46 hypercholesterolemics, 46 controls] were studied at standardized conditions. Baseline augmentation index (AIx) was assessed followed by the administration of 0.5 mg sublingual nitroglycerine, an endothelium independent vasodilator. AIx was assessed and the maximum change in AIx after nitroglycerine was recorded as EIV. After a washout period of 30 minutes, 400 µg of inhaled salbutamol, an endothelium dependent vasodilator was administered. AIx was assessed again and the maximum change in AIx after salbutamol was recorded as EDV. Global endothelial function was calculated as EDV:EIV ratio. EDV and EIV in patients with hypercholesterolemia compared to controls were 2.97 ± 3.95 and 6.65 ± 3.80 (p<0.001); and 13.41 ± 4.57 and 15.88 ± 4.78 (p=0.01) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls; 0.21 ± 0.38 and 0.44 ± 0.24 (p<0.001) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls. PWA is a potential clinical tool to assess global endothelial function in patients with hypercholesterolemia.
  • Xuezhikang alleviates lipid accumulation via AMPK activation in hepatocellular steatosis model Article

    Zhang, Jie; Tong, Chuan-Feng; Wan, Jing; Wang, Yang-Gan

    Resumo em Inglês:

    Abstract Xuezhikang (XZK) is an extract of Chinese red yeast rice. It has multiple protective effects in cardiovascular systems. However, the underlying mechanism by which XZK affects free fatty acid (FFA)-induced lipogenesis in hepatocellular steatosis model is still unknown. Herein, we investigated this mechanism in HepG2 cells. The HepG2 cells were treated with palmitate acid (PA) to induce lipogenesis. Then the PA-induced HepG2 cells were subsequently treated with XZK. After 24 h of treatment, we determined the intracellular triglyceride (TG) contents and average areas of lipid droplets. To study the involvement of AMPK signaling pathway, we pre-treated the PA-induced HepG2 cells with Compound C, an AMPK inhibitor, before XZK treatment. Expressions of p-AMPK and AMPK were determined by Western blot. The results showed that XZK decreased TG content and lipid accumulation in hepatocellular steatosis model. Compound C abolished the effects of XZK. These results demonstrated for the first time that XZK protects hepatocytes against lipid accumulation induced by free fatty acids. Its effects may be mediated by the activation of AMPK pathway.
  • Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway Article

    Mansour, Suzan Mohamed; Ibrahim, Rasha Youssef Mohammed

    Resumo em Inglês:

    Abstract Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich’s solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich’s ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3β, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways.
  • Exploring Work Satisfaction and Characteristics of Iraqi Pharmacist Workforce Article

    Al-Jumaili, Ali Azeez; Mohammed, Zayneb Ahmed; Yawuz, Mohammed Jamal; Ahmed, Kawther Khalid

    Resumo em Inglês:

    Abstract The objectives of this study were to describe work characteristics of Iraqi pharmacists, to compare pharmacist job satisfaction between private and public sectors and to assess factors influencing job satisfaction level. This cross-sectional study of pharmacists, their work sites and work satisfactions used an electronic questionnaire that was posted on Facebook pharmacy professional group from June to September 2018. The participants included pharmacists from all 18 Iraqi provinces. We used multiple linear regression to identify predictors of general job satisfaction among 13 pharmacist characteristics. We received 658 usable surveys. Approximately half (47.24%) of respondents indicated dissatisfaction with their primary workplace. Job performance, patient contact, satisfaction with manager, income and expectation satisfactions were significantly related with work satisfaction. Pharmacists working in the private sector had significantly more control over their workplace and higher satisfaction with manager, income and general satisfactions compared to those working in public sector. Pharmacists work in diverse settings across the public healthcare system, community pharmacies, private drug bureaus and academia. About half of them are dissatisfied with their primary workplace. The private sector has more satisfaction rate compared to the public sector. Thus, officials need to improve job environments in the public sector.
  • Chronic Lymphocytic Leukemia (CLL): evaluation of AKT protein kinase and microRNA gene expression related to disease pathogenesis Article

    Gomes, Lorena Caixeta; Resende, Rodrigo Ribeiro; Parreira, Ricardo Cambraia; Ferreira, Cláudia Natália; Reis, Edna Afonso; Duarte, Rita Carolina Figueiredo; Alves, Luan Carlos Vieira; Araújo, Sergio Schusterschitz da Silva; Carvalho, Maria das Graças; Sabino, Adriano de Paula

    Resumo em Inglês:

    Abstract The present study evaluated 56 patients diagnosed with Chronic Lymphocytic Leukemia (CLL) and a control group of 44 clinically healthy subjects with no previous history of leukemia. Genetic expressions of AKT and microRNAs were evaluated by quantitative PCR (qPCR). A significant increase in AKT gene expression in patients when compared to controls was observed (p = 0.017). When the patients were stratified according to Binet subgroups, a significant difference was observed between the subgroups, with this protein kinase appearing more expressed in the B+C subgroup (p = 0.013). Regarding miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients, when compared to controls. However, no significant differences were observed in these microRNA expressions between the Binet subgroups (A versus B+C). By contrast, miR-21 to miR-27a oncogenes showed no expression difference between CLL patients and controls. AKT protein kinase is involved in the signaling cascade that occurs with BCR receptor activation, leading to increased lymphocyte survival and protection against the induction of cell death in CLL. Thus, increased AKT protein kinase expression and the reduction of miR-let-7b and miR-26a, both tumor suppressors, may explain increased lymphocyte survival in CLL patients and may be promising markers for the prognostic evaluation of this disease.
  • Anticholinesterase activity of β-carboline-1,3,5-triazine hybrids Article

    Baréa, Paula; Barbosa, Valéria Aquilino; Yamazaki, Diego Alberto dos Santos; Gomes, Carla Maria Beraldi; Novello, Claudio R.; Costa, Willian Ferreira da; Gauze, Gisele de Freitas; Sarragiotto, Maria Helena

    Resumo em Inglês:

    Abstract The β-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-β-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine.
  • Intra and Extra-granular Disintegrant Properties of Modified Underutilised Red Lima Bean Starch in Paracetamol Tablet Formulation Article

    Okekunle, Mary Oluwaseun; Akin-Ajani, Olufunke Dorothy; Ekpukpon, Bridget Lucy; Odeku, Oluwatoyin Adepeju; Olu-Owolabi, Bamidele Iromidayo; Adebowale, Kayode Oyebode

    Resumo em Inglês:

    Abstract Red lima bean (Phaseolus lunatus Linn) Family Fabaceae, has been modified by succinylation and annealing, and used as intra- and extra-granular disintegrants at concentrations of 5 and 10 %w/w in paracetamol tablet formulation in comparison with corn starch BP. The starches were characterised using FT-IR spectroscopy, SEM, proximate analysis, physicochemical and functional properties. FT-IR spectrometry revealed characteristic peaks at 1575.53 and 1713.99 cm-1 for the succinylated starch while the annealed showed no significant difference from the native starch. Modifications did not alter the ovoid shape of the native starch but reduced the particle size. Succinylation improved water absorption capacity, solubility and swelling of lima bean starch but annealing reduced the parameters. Tablets with disintegrants of lima bean starches generally had higher crushing strengths and lower friability than tablets with corn starch. Modifications reduced the disintegration time of the tablets when the starches were incorporated intra-granularly, which suggested particle-particle bond interruption and destruction of hydrogen bonds as mechanism of disintegration. Tablets containing 10 %w/w succinylated red lima bean starch incorporated intra-granularly had the highest disintegration efficiency ratio, DER, indicating a great balance between mechanical and disintegration properties. Modified red lima bean starches incorporated intra-granularly into paracetamol tablets led to faster disintegration and could efficiently substitute corn starch as disintegrant.
  • Proton pump inhibitor deprescription: A rapid review Article

    Imparato, Renata Rodriguez; Toma, Tereza Setsuko

    Resumo em Inglês:

    Abstract Proton pump inhibitors (PPI) are drugs that suppress gastric acid secretion. Its use, without support from scientific evidence, can contribute to polypharmacy, lead to drug interactions and, in the long term, cause serious adverse reactions. Studies advise physicians to deprescribe PPI. A quick review of scientific evidence, also called a rapid systematic review, on the deprescribing of PPI was performed. Evidence searches were performed in the LILACS, Embase, PubMed and NICE evidence databases with the terms “omeprazole”, “proton pump inhibitors”, “deprescription”, “deprescribing”. At LILACS these descriptors were also used in Portuguese and Spanish. Of 118 studies identified, four systematic reviews were selected for analysis. Abrupt deprescribing was associated with an increased risk of symptom recurrence. Fear of symptom recurrence is one of the major barriers to patient-related deprescribing. Educational interventions directed at prescribers, pharmacists, and patients are effective strategies in the deprescribing of PPI. Deprescribing process showed to be feasible in different contexts, with different strategies. The process is most effective through actions with educational and guidance materials directed to health professionals and patients, and with the involvement or leadership of the pharmacist.
  • Synthesis, antimicrobial and antioxidant activities of pyridyl substituted thiazolyl triazole derivatives Article

    Tay, Naime Funda; Duran, Murat; Kayagil, İsmail; Yurttaş, Leyla; Göger, Gamze; Göger, Fatih; Demirci, Fatih; Demirayak, Şeref

    Resumo em Inglês:

    Abstract In this present study, 63 different 5-[4-methyl-2-(pyridin-3/4-yl)thiazole-5-yl]-4-substituted-3-substituted benzylthio-4H-1,2,4-triazole derivatives were synthesized, and evaluated for their in vitro antimicrobial activity against various human pathogenic microorganisms and antioxidant activity. The derivatives were synthesized in a multi-step synthesis procedure including triazole and thiazole ring closure reactions, respectively. The synthesized derivatives (A1-24; B1-39) were screened for their antibacterial, antifungal, and antioxidant activities compared to standard agents. The derivatives possessing 3-pyridyl moiety particularly exhibited relatively high antibacterial activity (MIC= < 3.09-500 µg/mL) against Gram-positive bacteria, and compounds possessing 4-pyridyl moiety showed remarkable antioxidant activity.
  • Development of fluorescent- and radio-traceable T1307-polymeric micelles as biomedical agents for cancer diagnosis: biodistribution on 4T1 tumor-bearing mice Article

    Lecot, Nicole; Rodríguez, Gonzalo; Stancov, Valentina; Fernández, Marcelo; González, Mercedes; Glisoni, Romina J.; Cabral, Pablo; Cerecetto, Hugo

    Resumo em Inglês:

    Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.
  • Single-center, retrospective study on changes in pain-relieving therapy after bone metastasis detection by bone scintigraphy in prostate cancer patients Article

    Silva, Thamyrys Bessa; Cardoso, Marcella Araugio Soares; Ramim, Jayda Eiras; Bergmann, Anke; Pujatti, Priscilla Brunelli

    Resumo em Inglês:

    Abstract Whole-body bone scintigraphy (WB-BS) is used for detecting and monitoring metastatic spread of prostate cancer (PCa) and to investigate bone pain episodes. To investigate the impact of a positive WB-BS on pain-relieving medicine prescription in PCa patients, a single-center, retrospective cohort study with PCa patients classified as positive for bone metastases (BM) by WB-BS was conducted. Demographic, clinical, and ambulatory pain-relieving medicine prescription data were evaluated. Pain-relieving medicines were categorized according to the WHO ‘Analgesic Ladder’. Regimens adopted before and after WB-BS were compared. Differences were considered significant at p<0.05. A total of 180 PCa patients were diagnosed with BM, 64.4% of whom were ≥65 years of age. Thirty-three patients were prescribed analgesics only after WB-BS, mostly including NSAIDs and weak opioids. Pain-relieving prescription changed after WB-BS in patients with prescriptions before and after WB-BS, with a reduction in NSAIDs and adjuvants and an increase in weak and strong opioids. In addition, 40% of patients with WHO analgesic step 1 drugs and 21.7% of patients with WHO step 2 drugs before WB-BS changed to other WHO steps after WB-BS. Pain-relieving prescriptions changed after a positive WB-BS, providing evidence that it could contribute to clinical management of painful metastatic PCa patients.
  • Effects of thymoquinone on alpha-amanitin induced hepatotoxicity in human C3A hepatocytes Article

    Katirci, Yavuz; Yilmaz, Ismail; Kaya, Ertugrul

    Resumo em Inglês:

    Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ’s effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.
  • Therapeutic drug monitoring of gabapentin: the applicability in patients with neuropathic pain Article

    Yamamoto, Priscila Akemi; Benzi, Jhohann Richard de Lima; Dach, Fabíola; Moraes, Natália Valadares de

    Resumo em Inglês:

    Abstract Gabapentin is an antiepileptic drug prescribed for several neuropathic pain conditions. This study aimed to evaluate gabapentin (GAB) trough plasma concentration range and the applicability of therapeutic drug monitoring in patients with neuropathic pain. Fifty-three patients with neuropathic pain, aged 20 to 75, received gabapentin as treatment for at least 7 days. Gabapentin plasma concentration was sampled before GAB administration and quantified by liquid chromatography with a UV detector. GAB trough plasma concentration ranged between 0.40 and 11.94 µg/mL in patients with chronic neuropathic pain. No differences were observed in terms of GAB plasma concentrations between responsive and non-responsive patients. Our data suggest that the reference ranges suggested in the literature for patients with epilepsy should not be used for patients with neuropathic pain. Therapeutic drug monitoring of GAB was shown to be an important tool to assess treatment adherence.
  • Semisolid formulations based on solid-in-oil-in-water systems containing proteins Article

    Araújo, Mónica; Marques, Ana Camila; Lobo, José Manuel Sousa; Amaral, Maria Helena

    Resumo em Inglês:

    Abstract In recent years, improvements have been made, through biotechnological processes, in the production and development of peptides capable of increasing collagen and elastin synthesis for anti-aging skin care. However, proteins have many limitations due to their structural, chemical and physical fragility to external aggressions, which may cause conformational changes, leading to loss of biological activity. Therefore, it is important to create delivery systems that protect these biomolecules from damage, allowing them to reach their target. This work aimed to develop a system able to carry bovine serum albumin (BSA), used as a model of a protein, and to incorporate this system in a semisolid formulation suitable for skin application. A microemulgel based on a solid-in-oil-in-water (S/O/W) microemulsion was prepared. Firstly, the association efficiency (AE) of lyophilized BSA-sucrose ester complex and the size of S/O nanodispersion were assessed; then, the characterization and stability evaluation of the final semisolid formulation through evaluation of pH, texture and rheological behavior were performed. The average value of AE was 54.74% ± 2.17. It was possible to develop an S/O/W microemulsion, which allowed the subsequent development of an S/O/W microemulgel that assured suitable pH, texture and rheological characteristics for skin application.
  • Smart Spectrophotometric Methods for Concurrent Determination of Furosemide and Spironolactone Mixture in Their Pharmaceutical Dosage Forms Article

    Lotfy, Hayam M.; El-Hanboushy, Sara; Fayz, Yassmin M.; Abdelkawy, Mohammed

    Resumo em Inglês:

    Abstract Simple, precise, accurate and specific spectrophotometric methods are progressed and validated for concurrent analysis of Furosemide (FUR) and Spironolactone (SPR) in their combined dosage form depend on spectral analysis procedures. Furosemide (FUR) in the binary mixture could be analyzed at its λmax 274 nm using its recovered zero order absorption spectrum using constant multiplication method (CM). Spironolactone (SPR) in the mixture could be analyzed at its λmax 238 nm by ratio subtraction method (RS). Concurrent determination for FUR and SPR in their mixture could be applied by amplitude modulation method (AM), absorbance subtraction method (AS) and ratio difference (RD). Linearity ranges of FUR and SPR were (2.0µg/mL-22.0 µg/mL) and (3.0µg/mL-30.0 µg/mL), respectively. Specificity of the proposed spectrophotometric methods was examined by analyzing the prepared mixtures in laboratory and was applied successfully for pharmaceutical dosage form analysis which have the cited drugs without additives contribution. The proposed spectrophotometric methods were also validated as per as the guidelines of ICH. Statistical comparison was performed between the obtained results with those from the official methods of the cited drugs, using one-way ANOVA, F-test and student t-test. The results are exhibiting insignificant difference concerning precision and accuracy.
  • Seasonal and pluviometric effects on the phenolic compound composition and antioxidant potential of Licania macrophylla Benth (Chrysobalanaceae), a medicinal plant from the Amazon rainforest Article

    Araujo, Ramon Diego Cunha; Costa, Anderson Luiz Pena da; Pinto, Jardel Barbosa; Silva, Luís Maurício Abdon da; Silva, Gabriel Araujo da

    Resumo em Inglês:

    Abstract Licania macrophylla is a medicinal plant from the Amazon. It is mainly used in the form of a decoction and has been reported to contain several phenolic compounds. However, the effect of seasonality on the phenolic composition and antioxidant potential of this plant has not been well studied, especially in the Amazon region, an area affected by the rainy and less-rainy seasons. Therefore, we evaluated the seasonality of these aromatic compounds and the antioxidant potential of the extracts from L. macrophylla stem bark. We also determined the correlation between the extraction methods used and precipitation levels during each period for 1 year. The total flavonoid and phenolic content, DPPH-scavenging potential, percentage of phosphomolybdenum complex reduction, and iron-reducing power were quantified. The levels of phenolic compounds were the highest in June, whereas those of flavonoids were the highest in September and October; however, these differences were not significant. The extracts from April, November, and June showed the best results for DPPH scavenging, phosphomolybdenum reduction, and iron reduction power, respectively. Significant differences in the phenolic content and DPPH-scavenging activity were observed between the more- and less-rainy seasons. The total phenolic content was positively correlated with FRAP and DPPH, whereas flavonoid levels were negatively correlated.
  • Formulation and evaluation of the vascular endothelial growth factor loaded polycaprolactone nanoparticles Article

    Kerimoğlu, Oya; Özer-Önder, Setenay; Alarçin, Emine; Karsli, Seher

    Resumo em Inglês:

    Abstract In an attempt to increase molecular stability and provide controlled release, vascular endothelial growth factor (VEGF) was encapsulated into polycaprolactone (PCL) nanoparticles. Both VEGF-free and VEGF-loaded PCL nanoparticles were formulated by w/o/w double emulsion of the dichloromethane-water system in the presence of polyvinyl alcohol (PVA) and rat serum albumin. To achieve the optimal formulation concerning particle size and monodispersity, studies were carried out with different formulation parameters, including PVA concentration, homogenization time and rate. Scanning electron microscopy and dynamic light scattering analysis showed respectively that particles had a spherical shape with a smooth surface and particle size varying between 58.68-751.9 nm. All of the formulations were negatively charged according to zeta potential analysis. In vitro release study was performed in pH 7.4 phosphate-buffered saline at 37°C and released VEGF amount was measured by enzyme-linked immunosorbent assay (ELISA) method. At the end of the 35th day, 10% of total encapsulated VEGF was released with a sustained-release profile, which fitted the Korsmeyer-Peppas kinetic model. The bioactivation of the nanoparticles was evaluated using XTT and ELISA methods. As a result, the released VEGF was biologically active and also VEGF loaded PCL nanoparticles enhanced proliferation of the human umbilical vein endothelial cells in cell culture.
  • Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp. Article

    Pittol, Vanessa; Veras, Kleyton Santos; Kaiser, Samuel; Danielli, Letícia Jacobi; Fuentefria, Alexandre Meneghello; Ortega, George González

    Resumo em Inglês:

    Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.
  • Impact of pharmacist intervention in patients with Alzheimer's disease Article

    Forgerini, Marcela; Lucchetta, Rosa Camila; Oliveira, Fernanda Mariana; Herdeiro, Maria Teresa; Capela, Marisa Veiga; Mastroianni, Patrícia de Carvalho

    Resumo em Inglês:

    Abstract To assess the therapy relative to indication, effectiveness, safety and adherence in patients with Alzheimer’s disease (AD). An interventional, prospective, non-randomized study was conducted in a single secondary care center in Brazil. The pharmacist-led medication therapy management (MTM) was conducted to detect drug-related problems (DRPs) at baseline and after six months of intervention. The health status outcomes (i.e. cognitive screening tests; levels of glucose; total cholesterol; triglycerides; thyroid stimulating hormone; serum free thyroxine and blood pressure) were measured. 66 patients with AD were included, of whom 55 patients completed the follow-up of six months. 36 patients (36/55) were non-adherent to AD drug therapy. Out of detected 166 DRPs, 116 were solved. Four patients were withdrawn from the AD protocol due to resolution of prodromal symptoms. On the conclusion of the study, the MTM improved and controlled blood pressure, glucose, total cholesterol, triglycerides levels (p<0.05). The pharmacist-led MTM was effective in solving 69.8% of DRPs, improving and controlling the clinical parameters evaluated.
  • Green synthesis of silver nanoparticles using leaf extracts of Mentha arvensis Linn. and demonstration of their in vitro antibacterial activities Article

    Thiyagarajan, Santhanamari; Kanchana, Subramanian

    Resumo em Inglês:

    Abstract A study was carried out to synthesize silver nanoparticles (Ag-NPs) using plant extracts and to explore their pharmaceutical application as antibacterial agents. Dried leaves of Mentha arvensis Linn. were powdered and extracts were prepared using three different organic solvents. Preliminary screening on antibacterial activity by agar well diffusion method indicated that the methanolic extract possessed higher potential than the other two. Phytochemical analysis of the leaf extract revealed that it possesses tannins, steroids, terpenoids and flavonoids. Ag-NPs prepared using this extract were of spherical to cuboidal shape ranging in size from 40 to 70 nm. It retained essential chemical groups and had the required surface plasmon resonance. Further to the antimicrobial assay, the Ag-NPs, in contrast to the whole methanolic leaf extract, showed better (100% vs. 80%) bactericidal activity against the indicator organisms. The zones of growth inhibition for gram positive bacteria ranged between 14±0.6 and 23±0.3, while it was between 12±0.6 and 22±0.2 for gram negative bacteria. The Ag-NPs presented the minimum inhibitory concentration values of 250 µg/mL for gram positive bacteria and 250 - 500 µg/mL for gram negative bacteria. These findings suggest that the natural compounds present in M. arvensis L. possess the potency to facilitate the synthesis and antibacterial action of Ag-NPs.
  • Direct-acting antivirals for chronic Hepatitis C are effective and safe: an observational study in Londrina/PR Article

    Machado, Hodnei Takashi; Guidoni, Camilo Molino

    Resumo em Inglês:

    Abstract This study aimed to evaluate the effectiveness and safety of direct-acting antivirals in a Unified Health System pharmacy of Londrina, Brazil. A descriptive observational study was performed from June 2017 to June 2018. Sociodemographic, clinical, and therapeutic variables of patients were collected from secondary data sources. Effectiveness was evaluated by sustained virologic response (SVR) and safety was evaluated by adverse events (AEs) and drug interactions (DIs). The mean population (N=30) was 56.6±11.3 years old and almost all patients had comorbidities (93.3%) and concomitant drugs (96.7%). Effectiveness evaluation was possible in 17 patients, and all of them (100.0%) achieved SVR. Eighteen patients (60.0%) reported 38 AEs, mostly mild, such as stomach symptoms and headache. No statistical relation was found between AE occurrence and treatment duration, Ribavirin use, number of comorbidities or number of concomitant drugs. A total of 48 DIs were reported, 18 being severe, and were managed by the pharmacist. The study indicates that the treatment was effective and safe.
  • Two-Step Purification of L-Asparaginase from Acrylaway® L Article

    Tundisi, Louise Lacalendola; Coêlho, Diego de Freitas; Faria, Alessandra Valéria de Sousa; Pessoa Junior, Adalberto; Tambourgi, Elias Basile; Nascimento, Laura de Oliveira; Silveira, Edgar; Mazzola, Priscila Gava

    Resumo em Inglês:

    Abstract L-Asparaginase (L-ASNase) is a biopharmaceutical used for acute lymphoblastic leukaemia (ALL) treatment, dramatically increasing the patients’ chance of cure. However, its production and distribution in developing countries were disrupted because of its low profitability, which caused great concern among patients. This study evaluates the feasibility of combining fractional precipitation and aqueous two-phase systems (ATPS) to purify L-ASNase from a low-grade product, commercially known as Acrylaway® L. The ATPS purification results were not particularly expressive compared to the two-step purification process composed of ethanol precipitation and gel filtration, which was able to recover the target molecule with a purification factor over 5 fold. Thus, we studied a purification process capable of manufacturing pharmaceutical grade L-ASNase from a commercially available low-grade raw material; however, improvements regarding its throughput must be achieved, and high purity is the first step to apply it as a new biopharmaceutical product. The proposed process could pose as a short-time solution to mitigate its shortage while a cost-effective production plant is being developed.
  • Application of HACCP for development of quality risk management in a water purification system Article

    Costa, Mayre Aparecida Borges da; Brandão, Amanda Lemette Teixeira; Pinto, José Carlos; Nele, Márcio

    Resumo em Inglês:

    Abstract The present work reports the implementation of the Hazard Analysis Critical Control Point (HACCP) methodology to analyze the water purification system of a pharmaceutical site, in order to assure the system quality and prevent failures. As a matter of fact, the use of HACCP for development and implementation of Quality Risk Management (QRM) is not usual in pharmaceutical plants and it is applied here to improve the performance of the water purification system of a polymerization pilot plant used to manufacture pharmaceutical grade polymer microparticles. Critical Control Points (CCP) were determined with the aid of a decision tree and questions were made to characterize whether identified hazards constitute actual CCPs and should be monitored. When deviations were detected, corrective actions were performed and action plans were used for following-up and implementation of corrective actions. Finally, microbiological and physicochemical parameters were analyzed and the obtained results were regarded as appropriate. Therefore, it is shown that HACCP constitutes an effective tool for identification of hazards, establishment of corrective actions and monitoring of the critical control points that impact the process and the quality of the final pharmaceutical product most significantly.
  • Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis Article

    Yener, Beytul; Erkmen, Cem; Uslu, Bengi; Goger, Nilgun Gunden

    Resumo em Inglês:

    Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.
  • Perception of pharmacists regarding human resources, training, and development of a national hospital pharmacy: a preliminary report on Basel Statements Article

    Rocha, Bruna Gabriela; Silva, Aline Michelle Silveira; Pereira, Mariana Linhares; Baldoni, André Oliveira; Ayres, Lorena Rocha; Penm, Jonathan; Moles, Rebekah; Sanches, Cristina

    Resumo em Inglês:

    Abstract The hospital pharmacy needs a constant process of evaluation and monitoring of its activities. In Brazil, several agencies establish tasks and duties for pharmacists, but little is known about the compliance and the perception of the professional regarding these policies. The present study aims to characterize the pharmacist’s perception of Brazilian hospital pharmacy policies according to the Basel Statements. A search was performed for the contacts of all medium and high complexity hospitals in the country. Subsequently, a questionnaire elaborated following the Basel Statements was sent by e-mail to hospital pharmacists throughout the country. The domain analyzed was "Human Resources, Training, and Development". Statistical analyses were performed using SPSS 19.0. Pharmacists representing a total of 111 hospitals from all Brazilian regions answered the survey questionnaire and showed that more than half of the hospital pharmacists perceive themselves as not complying, whether in the service of local, national, or pharmaceutical education. Besides updating the professionals in relation to national policies, it is necessary that the representative bodies of the pharmaceutical class be more present in the elaboration and evaluation of the policies directed to human resources, seeking uniformity and the possibility of carrying out the activities required.
  • QbD enabled Process Variable Study to Develop Sustained Release Chitosan-Alginate Embedded Delivery System for Improved Patient Compliance Article

    Sharma, Vijay; Singh, Lalit; Verma, Navneet

    Resumo em Inglês:

    Abstract The current investigation entail systematic Quality by Design (QbD)-enabled approach for the development of Sustained released embedded drug delivery systems of L-Arginine employing ionic gelation technique to attain improved patient compliance. Hence, in this QbD enabled systematic approach; quality target product profile (QTTP) was defined and critical quality attributes (CQAs) were identified. Further the risk assessment studies were undertaken through Ishikawa fish bone diagram to locate the critical material attributes (CMAs) and/or critical process parameters (CPPs) for the formulation of beads that may affect CQAs of drug product. A face centered central composite design (CCD) for two factors at three levels each with α =1 was employed for the optimization process to checkout the impact of concentration of sodium alginate and concentration of chitosan as CMAs which wereprior identified from risk assessment study and further evaluated for CQAs viz. bead size, swelling index and percent drug entrapment. The optimum formulation was embarked upon by using mathematical model being developed yielding desired CQAs. Thereby chitosan coated calcium-alginate delivery system was successfully developed by strategically employing QbD approach.In a nutshell, the presentinvestigation reports the successful development of optimized chitosan coated alginate beads employing QbD approach which can serve as a platform for other drugs too.
  • The pharmacist’s role on transgender care: findings from a literature review Article

    Pinho, Arthur Antunes de Souza; Silva Filho, Claudio Claudino da; Silva, Daniel Tenório da; Nunes, Deuzilane Muniz; Silva, Susanne Pinheiro Costa e; Pio, Isabel Dielle

    Resumo em Inglês:

    Abstract Transgender is a broad-spectrum term referring to people who do not match their assigned sex at birth. Several issues, including social detachment, poor access to healthcare services, and the lack of social/economic opportunities, have historically affected this population. In this scenario, pharmacists - not mentioned in national and international clinical guidelines/protocols regarding transgender care - might be key professionals to serve and care for this population. The main goal of this literature review was to identify the pharmacists’ role in the care of transgender people. The articles were retrieved from scientific databases. After applying filters (e.g., language, full-text availability, and coverage of the research question), seven articles were included in this review. The articles did not present pharmaceutical experiences or practices regarding transgender healthcare. Instead, some articles stressed the inadequate or inappropriate use of hormones and their side effects, also covering the role of this issue in professional development, gaps, and potential opportunities for research and pharmaceutical services. Pharmacists, included in a multi-professional team, could be a key element to promote access to healthcare and the well-being of the transgender population.
  • Exopolysaccharides from Klebsiella oxytoca: anti-inflammatory activity Article

    Bannwart, Thays Avelino; Bersani-Amado, Ciomar Aparecida; Ames, Franciele Queiroz; Siqueira, Vera Lúcia Dias; Oliveira, Arildo José Braz de; Gonçalves, Regina Aparecida Correia

    Resumo em Inglês:

    Abstract Exopolysaccharides (EPS) produced by Klebsiella oxytoca are of environmental, pharmaceutical, and medicinal interest. However, studies about the anti-inflammatory activity of EPS produced by this microorganism still remain limited. The aim of this study was to produce, characterize, and evaluate the anti-inflammatory activity of EPS from K. oxytoca in a pleurisy model. Colorimetric analysis revealed that precipitated crude exopolysaccharides (KEPSC) and deproteinated exopolysaccharides (KEPS) present high levels of total carbohydrates (65.57% and 62.82%, respectively). Analyses of uronic acid (7.90% in KEPSC and 6.21% in KEPS) and pyruvic acid (3.01% in KEPSC and 1.68% in KEPS) confirm that the EPS are acidic. Gas chromatography-mass spectrometry analyses demonstrated that the EPS consisted of rhamnose (29.83%), glucose (11.21%), galactose (52.45%), and mannose (6.50%). The treatment of an experimental pleurisy model in rats through subcutaneous administration of 50, 100, 200, and 400 mg/kg of KEPS decreased both the volume of inflammatory exudate and the number of leukocytes recruited to the pleural cavity. The present data showed that EPS production by K. oxytoca using the method described is easy to perform and results in a good yield. In addition, we show that KEPS exhibit anti-inflammatory activity when administered subcutaneously in rats.
  • Leaf extract of Coffea arabica L. reduces lipid peroxidation and has anti-platelet effect in a rat dyslipidemia model Article

    Simões, Mario Henrique Souza; Salles, Bruno Cesar Correa; Duarte, Stella Maris da Silveira; Silva, Marcelo Aparecido da; Viana, André Luiz Machado; Moraes, Gabriel de Oliveira Isaac de; Figueiredo, Sonia Aparecida; Ferreira, Eric Batista; Rodrigues, Maria Rita; Paula, Fernanda Borges de Araújo

    Resumo em Inglês:

    Abstract This study aimed to evaluate the antioxidant potential of the Coffea arabica Lineu (L.) leaf extract and its effects on platelet aggregation of dyslipidemic rats. The extract was obtained by the percolation of C. arabica L. leaves in hydroethanolic solution 70% (v/v). The mass spectrometry FIA-ESI-MS² suggested the presence of chlorogenic acid, rutin acid, and quinic acid. The DPPH• radicals scavenging capacity was demonstrated (IC50 = 0.06 mg/mL). The extract was administered to rats by gavage (300 mg/kg/day) for 56 days. Dyslipidemia was induced by administering Triton WR-1339 (300 mg/kg body weight) on the 54th day. On day 56, blood was collected by puncturing the abdominal aorta artery and the aortic artery was removed. Lipid profile, markers of renal and hepatic injury, lipid peroxidation, and platelet aggregation tests were carried out. The ingestion of extract reduced the lipid peroxidation (aorta and plasma) and platelet aggregation in dyslipidemic rats. The extract did not affect markers of renal and hepatic function as analyzed in this study, suggesting neither impaired liver nor kidney function in these animals. Therefore, our results demonstrate that the extract of leaves of C. arabica L. show antioxidant potential in vitro and in vivo as well as anti-platelet aggregation in dyslipidemic animals.
  • Coagulase-negative staphylococci isolates from blood cultures of newborns in a tertiary hospital in southern Brazil Article

    Rampelotto, Roberta Filipini; Coelho, Silvana Silveira; Franco, Laísa Nunes; Mota, Augusto Dias da; Calegari, Luciano Fernandes; Jacobi, Luciane Flores; Hörner, Rosmari

    Resumo em Inglês:

    Abstract Neonatal sepsis continues to be a major cause of morbidity and mortality worldwide. Coagulase-negative staphylococci (CoNS), commonly found on the skin, being the main agents isolated. The aim of this study was to evaluate CoNS isolated from blood cultures of newborn (NB) infants. The study took place between 2014 and 2016/2017 in a tertiary hospital in southern Brazil. Using the VITEK 2 system (bioMérieux, Marcy l'Etoile, France), the microorganisms were identified and had their sensitivity profiles determined. The minimum inhibitory concentrations of linezolid, tigecycline, and vancomycin were also determined. The clinical parameters and mortality rates of NBs were evaluated. From January to December 2014, 176 CoNS isolates were obtained from 131 patients and from June 2016 to July 2017, 120 CoNS isolates were obtained from 79 patients. Staphylococcus epidermidis was most prevalent in both periods. Resistance rates increased between 2014 and 2016/2017, especially against ciprofloxacin (52.27% and 73.11%, p = 0.0004), erythromycin (51.40% and 68.07%, p = 0.0054), gentamicin (50.59% and 67.23%, p = 0.0052), and penicillin (71.3% and 99.17%, p = 0.0001), respectively. With 100% susceptibility to linezolid, tigecycline, and vancomycin in both periods and methodologies tested. In 2014, 53.44% of the NBs received antibiotic therapy, and of these, 77.14% used a catheter; in 2016/2017, these were 78.48% and 95.16%, respectively. Regarding laboratory tests, a hemogram was ineffective, since patients with sepsis presented normal reference values. In 2014 and 2016/17, 15.71% and 17.74% of the NBs died, respectively. S. epidermidis was the predominant microorganism, related to catheter use in most cases. The resistance rates have increased over time, demonstrating the importance of adopting control and prevention measures in this hospital. CoNS are responsible for a significant neonatal sepsis mortality rate in infants.
  • Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais Article

    Costa, Anna Carolina de Moura; Freitas, Laura Maciel de; Tranin, Geny Carolina Gomes; Sales, Thais Lorenna Souza; Pestana, Ana Cristina Nogueira Rodrigues; Alpoim, Patrícia Nessralla; Sanches, Cristina; Chequer, Farah Maria Drumond

    Resumo em Inglês:

    Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.
  • Physicochemical characterization and cosmetic applications of Passiflora nitida Kunth leaf extract Article

    Ribeiro, Priscilla Tobias; Pedrosa, Tatiana do Nascimento; Chaves, Francisco Celio Maia; José Quintans-Júnior, Lucindo; Araújo, Adriano Antunes de Souza; Vasconcellos, Marne Carvalho de; Maria-Engler, Silvya Stuchi; Silva, Cláudia Cândida; Silva, Felipe Moura Araújo da; Koolen, Héctor Henrique Ferreira; Lima, Emerson Silva; Lima, Ádley Antonini Neves de

    Resumo em Inglês:

    Abstract Passiflora nitida Kunth, an Amazonian Passiflora species, is little studied, although the specie’s high biological potential. Herein the plant’s pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent. P. nitida dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1 and tyrosinase inhibition between 400-654 μg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that P. nitida extract has promising features for the development of cosmetic formulations.
  • In vitro release mechanism and cytotoxic behavior of curcumin loaded casein nanoparticles Article

    Jenifer, Josphine; Upputuri, Ravi Theaj Prakash

    Resumo em Inglês:

    Abstract In the recent past, drug delivery through nanoparticles is considered an effective tool to treat various diseases. Biopolymeric nanoparticles such as protein based nanoparticles have vital role as drug carrier as it is non-antigenic, and easily biodegradable. Curcumin, plant polyphenolic anticancerous compound was loaded into the casein nanoparticles by coacervation method. Particle size and surface charge of spherical casein nanoparticles as observed to be 201.4 nm and -86.9 mV. The loading efficiency of curcumin loaded casein nanoparticles was found to 85.05 %. In vitro drug release was performed at different pH (7.4 and 3.0), and the cumulative release was observed to be 24.8 and 20.13% and at different temperatures (25°C and 37°C), the cumulative release was observed to be 24.8 and 28.60 % respectively in 48 h. Curcumin release from casein nanoparticles was shown to be in a steady, and prolonged rate. The nanoparticles were observed to have an effective antimocrobial activity than curcumin in free form. The drug loaded casein nanoparticles were found to be potent particles to protect cells from hydrogen peroxide and UV light damage. The cytotoxic activity of nanoparticles on MCF7 and A549 cells were assayed and was observed to have an IC50 value of 609 and 825.2µg/ml. Cell death was observed to be through apoptosis, accompanied by DNA fragmentation.
  • Patients’ medication reconciliation in a university hospital Article

    Magalhães, Gabriella Fernandes; Rosa, Mário Borges; Noblat, Lúcia Araújo Costa Beisl

    Resumo em Inglês:

    Abstract Medication reconciliation is a strategy to minimize medication errors at the transition points of care. This study aimed to demonstrate the effectiveness of medication reconciliation in identifying and resolving drug discrepancies in the admission of adult patients to a university hospital. The study was carried out in a 300-bed large general public hospital, in which a reconciled list was created between drugs prescribed at admission and those used at pre-admission, adapting prescriptions from the pharmacotherapeutic guidelines of the hospital studied and the patients’ clinical conditions. One hundred seven patients were included, of which 67,3% were women, with a mean age of 56 years. Two hundred twenty-nine discrepancies were found in 92 patients; of these, 21.4% were unintentional in 31.8% of patients. The pharmacist performed 49 interventions, and 47 were accepted. Medication omission was the highest occurrence (63.2%), followed by a different dose (24.5%). Thirteen (26.5%) of the 49 unintentional discrepancies included high-alert medications according to ISMP Brazil classification. Medication reconciliation emerges as an important opportunity for the review of pharmacotherapy at transition points of care, based on the high number of unintentional discrepancies identified and resolved. During the drug reconciliation process, the interventions prevented the drugs from being misused or omitted during the patient’s hospitalization and possibly after discharge.
  • Determination of perindopril erbumine by oxidative coupling reaction using 2, 6-dichloroquinone-4-chlorimide Article

    Thuttagunta, Manikya Sastry; Karipeddi, Ramakrishna

    Resumo em Inglês:

    Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 μg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines.
  • Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation Article

    Rathore, Sajjan Singh Seema; Geetha, Muniyappa; Manjula, Basappa Palur; Joshi, Vijaya Gopalachar; Setty, Siddamsetty Ramachandra

    Resumo em Inglês:

    Abstract Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 μ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer.
  • Pharmaceutical co-crystals of posaconazole for improvement of physicochemical properties Article

    Nijhawan, Monika; Godugu, Monika; Saxena, Trapti; Farheen, Talat; Dwivedi, Kanchan

    Resumo em Inglês:

    Abstract Posaconazole exerts an extended spectrum of antifungal activity against various strains of clinically relevant moulds and yeasts. In recent years, antifungal triazole posaconazole has become increasingly important for the prophylaxis and treatment of systemic mycoses. After oral administration of posaconazole, absolute bioavailability has been estimated to range from 8% to 47%. Pharmaceutical co-crystallization is a promising approach for improving dissolution rate or manipulating other physical properties of API. The objective of this study is to improve the dissolution rate of posaconazole by co-crystallization. A 1:1 stoichiometric co-crystals of adipic acid were prepared by solvent assisted grinding method. The prepared co-crystals were subjected to solid-state characterization by FTIR, PXRD and DSC studies. The physicochemical properties of posaconazole and co-crystals were assessed in terms of melting point, flowability and dissolution rate. The results indicated improvement in flow property and dissolution rate. In vitro dissolution profile of co-crystals showed a significant increased dissolution of posaconazole from initial period in 0.1 N hydrochloric acid solution. The dissolution efficiency for posaconazole-adipic acid co-crystal was 61.65 % against posaconazole, 46.58 %. Thus, co-crystallization can be a promising approach to prepare posaconazole-adipic acid co-crystals with improved physicochemical properties.
  • The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats Article

    Milevic, Ana; Simic, Marko; Tomovic, Marina; Rankovic, Marina; Jakovljevic, Vladimir; Bradic, Jovana

    Resumo em Inglês:

    Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.
  • Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats Article

    Wang, Meng-Meng; Hao, Gang; Qu, Yu-Chen; Chen, Li; Hua, Wen-Yan; Zong, Shun-Lin; Wang, Meng; Su, Cun-Jin; Zhang, Quan-Ying; Du, Zi-Yan; Yu, Yun-Li

    Resumo em Inglês:

    Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.
  • Compatibility and efficiency of preservatives in emulsive cosmetics containing high surfactant content Article

    Schmitt, Priscila de Oliveira; Fischer, Ana Flávia; Silva, Ruth Meri Lucinda da; Cruz, Alexandre Bella

    Resumo em Inglês:

    Abstract The objective of this study was to determine the influence of nonionic surfactants on the effectiveness of preservatives used in emulsions containing high surfactant content. Mixtures of different concentrations were prepared between polyethoxylated (40) hydrogenated castor oil (PHCO) and polyoxyethylene sorbitan monooleate (PSO), with methylparaben, phenoxyethanol, methylparaben, ethylparaben, propylparaben, and isobutylparaben (PMEPBI) blend, phenoxyethanol and benzoic acid (BP) blend, and phenoxyethanol and caprylyl glycol (PC) blend. Subsequently, the compatibility of the formulation ingredients and the effectiveness of the preservatives were evaluated by the challenge test. It was found that PHCO and PSO inactivated the antimicrobial action of methylparaben and PMEPBI. Paraben-free preservatives BP and PC had less influence on surfactants than systems containing parabens. When incorporated into microemulsions and nanoemulsions containing 40% and 20% surfactants, methylparaben and BP 0.2% and 0.5% were only effective against Aspergillus niger. The PMEPBI 0.2% was effective as a preservative in nanoemulsified formulations against A. niger, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results demonstrate that the efficacy of the preservative system in formulations containing nonionic surfactant excipients depends on the type of excipient, the components of the formulation, the preservative systems composition, the excipient to preservative ratio, and the availability in the formulation.
  • Validation of the Brazilian version of the hepatitis B quality of life evaluation instrument - HBQOL, and its application to patients with chronic hepatitis B in Cascavel - PR Article

    Balbinot, Jessica Cristina; Souza, Astrid Wiens; Pontarolo, Roberto; Boeira Junior, Orli Dutra; Silva, Edson Antonio Alves da; Junges, Daniele Schaab Boff; Reis, Camila Borges dos; Venson, Rafael; Oliota, Ana Flavia Redolfi; Sanches, Andreia Cristina Conegero

    Resumo em Inglês:

    Abstract The objective of this study is to validate the specific questionnaire for Hepatitis B HBQOL (Hepatitis B Quality of Life Instrument, version 1.0) for the Brazilian version, in addition to testing its applicability in patients with hepatitis B under treatment and comparing the quality of life between patients using first-line drugs (tenofovir and entecavir). For the validation, the back-translation technique was used in a sample of 47 patients. Factor analysis was performed between the items in each domain of the questionnaire and the internal consistency was calculated using Cronbach's α coefficient. In assessing the applicability of the validated questionnaire, interviews were carried out with 124 patients. Sociodemographic and treatment data were collected to characterize the sample and perform correlation analyzes. The results demonstrate that the Brazilian version of the questionnaire was successfully validated. In the analysis carried out among the 124 patients, the domains psychological well-being and stigma obtained the highest scores in quality of life and the lowest level of education conferred better results in these two domains. The comparison between tenofovir and entecavir showed no significant difference in patients' quality of life. The use of this validated instrument can make therapeutic decisions more rational.
  • Synthesis and characterization of chitosan-PVA hydrogel containing PEGylated recombinant epidermal growth factor on cell culture for wound healing substitute Article

    Doğan, Murat; Şahbaz, Sevinç; Uğurlu, Timuçin; Sezer, Ali Demir

    Resumo em Inglês:

    Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.
  • Anti-Snake Venom Properties of Medicinal Plants: A Comprehensive Systematic Review of Literature Article

    Liaqat, Aroosa; Mallhi, Tauqeer Hussain; Khan, Yusra Habib; Khokhar, Aisha; Chaman, Sadia; Ali, Muhammad

    Resumo em Inglês:

    Abstract Snakebite is one of the major health issues posing considerable morbidity and mortality. According to an estimate of World Health Organization (WHO) (World health organization, 2021) approximately 5 million people are bitten by several species of snakes resulting in up to 2.5 million envenomation cases annually. The mainstay of treatment for envenomation is intravenous administration of anti-snake venom. Although antivenom neutralizes the systemic effects but it does not relieve the symptoms such as venom-induced hemorrhage, necrosis and nephrotoxicity. Moreover, the use of antivenoms is associated with hypersensitivity reactions including urticaria, anaphylaxis, or serum sickness due to their heterologous property. Furthermore, stringent storage conditions and narrow specificity of antivenoms limit their use in both developed as well as developing countries. In this context, researchers have been searching for natural products and plant extracts to explore their antivenom activity along with anti-myotoxic, anti-hemorrhagic and anti-inflammatory properties. Plant remedies may prove to be an effective alternate for antivenom sera with less adverse events and better tolerability. To the best of our knowledge, this is the first comprehensive review of medicinal plants possessing anti-snake venom activities against certain species of snakes. The current review highlights the investigated plants with their phytochemical analysis to integrate the available information for future research and development of antivenom sera.
  • Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis Article

    Li, Jie; Gu, Ping; Tong, Rong-Sheng; Wang, JiaFeng; Zhang, ShuHan; He, Dan; Li, Jin-Qi

    Resumo em Inglês:

    Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1β, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1β, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination.
  • Profiling the physicochemical and solid state properties of edible Tetracarpidium conophorum oil and its admixtures for drug delivery Article

    Umeyor, Chukwuebuka Emmanuel; Dan-Ejih, Faithline; Okonkwo, Amarachukwu Ukamaka; Umeyor, Immaculeta Chikamnele; Attama, Anthony Amaechi

    Resumo em Inglês:

    Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.
  • In silico investigation on the probable macromolecular drug targets involved in the anti-schizophrenia activity of Nardostachys jatamansi Article

    Wei, Foong Xi; Gaurav, Anand; Al-Nema, Mayasah

    Resumo em Inglês:

    Abstract Existing medications i.e. the antipsychotic drugs are known to be effective in treating only the positive symptoms of schizophrenia, while being ineffective on negative and cognitive symptoms of the disease. In addition, these medications cause extrapyramidal symptoms, forcing many patients towards natural medicine in the hope of minimizing the unwanted adverse effects. Nardostachys jatamansi is a medicinal plant that has been traditionally prescribed for various types of brain disorders. The active constituents of the plant have beneficial effects on the negative and cognitive symptoms of schizophrenia. This study was designed to identify the active constituents of Nardostachys jatamansi with the highest binding affinities for the key macromolecular drug targets involved in the pathophysiology of schizophrenia and thereby elucidate the possible mechanism of action. These targets are dopamine receptors, Gamma-aminobutyric acid receptors, N-methyl-D-aspartate receptors and Phosphodiesterase 10A. The results of molecular docking showed that, β-sitosterol, chlorogenic acid, oleanic acid and ursolic acid, displayed high binding affinity toward all the macromolecular drug targets. Ligands with steroid backbone and pentacyclic triterpene structure have been found to possess high binding affinity toward the dopamine receptor and phosphodiesterase 10A. While ligands with carbonyl group form stronger binding interactions with the N-methyl-D-aspartate receptor.
  • Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats Article

    Sweidan, Kamal; Sheikha, Ghassan Abu; Shattat, Ghassan; Al-qirim, Tariq; Bkhaitan, Majdi

    Resumo em Inglês:

    Abstract A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease.
  • Asymmetric Opening of Mitochondrial Permeability Transition Pore in Mouse Brain Hemispheres: A Link to the Mitochondrial Calcium Uniporter Complex Article

    Batool, Mehvish; Fayyaz, Hajra; Alam, Muhammad Rizwan

    Resumo em Inglês:

    Abstract The prolonged entry of large amounts of calcium into the mitochondria through the mitochondrial calcium uniporter complex (MCUC) may cause the permeability transition pore (mPTP) to open, which contributes to the pathogenesis of several diseases. Tissue-specific differences in mPTP opening due to variable expression of MCUC components may contribute to disease outcomes. We designed this study to determine differential mPTP opening in mitochondria isolated from different regions of mouse brain and kidney and to compare it with the expression of MCUC components. mPTP opening was measured using mitochondria isolated from the left/right brain hemispheres (LH/RH, respectively) and from kidney cortex/medulla, while the expression level of MCUC components was assessed from total cellular RNA. Interestingly, LH mitochondria showed less calcium-induced mPTP opening as compared to RH mitochondria at two different calcium concentrations. Conversely, mPTP opening was similar in the renal cortex and renal medulla mitochondria. However, the kidney mitochondria demonstrated bigger and faster mPTP opening as compared to the brain mitochondria. Furthermore, asymmetric mPTP opening in the LH and RH mitochondria was not associated with the expression of MCUC components. In brief, this study demonstrates thus far unreported asymmetric mPTP opening in mouse brain hemispheres that is not associated with the mRNA levels of MCUC components.
  • Effect of Spirulina on Lipid Profile, Glucose and Malondialdehyde Levels in Type 2 Diabetic Patients Article

    Rostami, Hormat Alsadat Azmand; Marjani, Abdoljalal; Mojerloo, Mohammad; Rahimi, Behdad; Marjani, Majid

    Resumo em Inglês:

    Abstract The study aimed to assess possible spirulina effects on lipid profile, glucose, and malondialdehyde levels in new cases of type 2 diabetes. The subjects consisted of 30 new cases of types 2 diabetes that divided into two groups; each consisted of 15 diabetic patients. Group I did not take any functional food or supplement and received no spirulina supplementation. Group II or experimental group also did not take any functional food or supplement but received spirulina supplementation. Analysis of data was done using SPSS 16.0. The Kolmogorov-Smirnov test, paired t-test, Wilcoxon test, and Spearman correlation analysis were used to analyze the data. After eight weeks of spirulina supplementation, significant differences were shown in the serum levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and malondialdehyde. The serum fasting blood glucose, lipid profiles, and malondialdehyde levels at baseline were negatively and positively correlated with changes in these parameters. Spirulina supplementation may have a beneficial effect on lipid profile and malondialdehyde (MDA) levels through an interventional 8 weeks. This effect may protect subjects against free radicals and the development of some diseases such as atherosclerosis. The spirulina supplementation also showed a potential lipid-lowering effect on new case type 2 diabetic patients which may help the diabetics to have control on lipid levels. In addition, spirulina may be used as a functional food for the management of lipid profiles and MDA levels.
  • Inclusion complexes of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin with 2-hydroxypropyl-(-cyclodextrin: solubility and antimicrobial activity Article

    Hadžiabdić, Jasmina; Špirtović-Halilović, Selma; Osmanović, Amar; Zahirović, Lejla; Elezović, Amar

    Resumo em Inglês:

    Abstract The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-β-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-β-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-β-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.
  • Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord Article

    Zhang, Rongbo; Zhang, Shuijing; Xu, Bin; Wu, You; Liang, Shunli; Hou, Bonan; Wang, Mimi; Liu, Jin; Yuan, Qiang

    Resumo em Inglês:

    Abstract We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC.
  • An overview of preparation and characterization of solid binary system and its application on transdermal film with variation of plasticizers Article

    Kahali, Nancy; Khanam, Jasmina; Chatterjee, Himadrija

    Resumo em Inglês:

    Abstract Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPβCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability.
  • Effect of carrier materials on the properties of the andrographolide solid dispersion Article

    Zhang, Shoude; Zeng, Qingyun; Zhao, Guowei; Dong, Wei; Ou, Liquan; Cai, Ping; Liao, Zhenggen; Liang, Xinli

    Resumo em Inglês:

    Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.
  • Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities Article

    Nguyen, Tu Thanh Thi; Do, Phuong Thi; Pham, Anh Van Thi; Nguyen, Huong Giang Thi Tran; Nguyen, Lan Ngoc Thi; Nguyen, Trang Tuyet

    Resumo em Inglês:

    Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5βH-9βH-iridoid-1α-O-(6′-O-(6,7-dihydrofoliamenthonyl)-β-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6′-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal.
  • Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers Article

    Falsoni, Raiana Maria Prucoli; Moraes, Flavia de Souza Andrade; Rezende, Mahira Sabino de; Silva, Cristiane Lyrio da; Andrade, Tadeu Uggere de; Brasil, Girlandia Alexandre; Lima, Ewelyne Miranda de

    Resumo em Inglês:

    Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.
  • Sunitinib induced resistance of endothelial cells by up-regulating P-glycoprotein and PI3K/Akt pathway Article

    Zhang, Rong; Huang, Limin; Pan, Di; Zhang, Wen

    Resumo em Inglês:

    Abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling.
  • Selective Cytotoxic effect of Probiotic, Paraprobiotic and Postbiotics of L.casei strains against Colorectal Cancer Cells: Invitro studies Article

    Elham, Noroozi; Naheed, Mojgani; Elahe, Motevaseli; Hossein, Modarressi Mohammad; Majid, Tebianian

    Resumo em Inglês:

    Abstract This study highlights the cytotoxic effect of three L. casei strains on colorectal cell lines in invitro conditions. Different concentrations of live, heat killed (HK) and cell free supernatant (CFS) of three L.casei strains were subjected to CaCo2 and MRC5 cell lines. The viability of the treated and untreated cells was determined after 72 hrs by MTT assay, and IC50 estimated. Apoptosis was evaluated by Annexin V-propidium iodide method using flow cytometry. The live, HK and CFS of the L. casei strains showed cytotoxic effects on colorectal cell lines with significant differences. The cytotoxicity effects of live cells on CaCo2 cells were significantly higher (p˂0.01) than the HK cells. A dose dependent response was observed, as higher concentrations resulted in enhanced cytotoxicity effects. Live L.casei 1296-2cells inhibited 91% of CaCo2 cell growth, with IC50 of less than 108 cfu/ml. MRS medium and concentrations of CFS at above 20% v/v, were cytotoxic to the normal cell lines. Flow cytometry analyses of L. casei 1296-2 indicated that cytotoxicity effects on CaCo2 cells is related to apoptotic induction. Invitro studies indicate that Live and CFS of L. casei 1296-2 might be promising candidate for the control of colorectal cancers.
  • Erratum Errata

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
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