Brazilian Journal of Pharmaceutical Sciences, Volume: 53, Issue: 3, Published: 2017
  • Impact Factor: an appropriate criterion for the Qualis journals classification in the Pharmacy area? Editorial

    Farias, Mareni Rocha; Storb, Bernd Heinrich; Storpirtis, Silvia; Leite, Silvana Nair
  • Decades of research in drug targeting using gastroretentive drug delivery systems for antihypertensive therapy Review

    Porwal, Amit; Dwivedi, Harinath; Pathak, Kamla

    Abstract in English:

    ABSTRACT The limitations in absorption of drugs with narrow absorption window, or those unstable in the intestinal pH or those exhibiting low solubility at high pH are primary candidates for gastroretentive drug delivery systems (GRDDS). The delivery system has been widely explored for its commercial potential for a wide variety of therapeutic agents. GRDDS offer clinical therapeutics for acute and chronic management. Hypertension is a chronic disease that requires long term treatment and its management by patient compliant dosage forms would be clinically useful. Antihypertensives belonging to different classes have proved good candidates for the formulation of GRDDS. The review aims to discuss various GRDDS researched for antihypertensive drugs to increase the gastric residing time, bioavailability, henceforth to reduce the dose of the drug, dosing frequency and increase patient compliance. It also explores various marketed products and the patents filed/granted for GRRDS of antihypertensives. The GRDDS investigated include effervescent and non-effervescent floating drug delivery systems, swelling and expanding systems and bio/mucoadhesive systems. Many other systems that provided research platforms include high density systems, raft forming systems and osmotic delivery systems. In clinical context, wherein combination of antihypertensives is indicated, dual release delivery systems may also be explored.
  • Arginine enzymatic deprivation and diet restriction for cancer treatment Review

    Zam, Wissam

    Abstract in English:

    ABSTRACT Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo- and radio-therapeutic approaches to be co-applied.
  • Development and characterization of pullulan-polymethacrylate free films as potential material for enteric drug release Article

    Lima, Isabela Angeli de; Pomin, Suelen Plaza; Cavalcanti, Osvaldo Albuquerque

    Abstract in English:

    ABSTRACT Free films of pullulan-polymethacrylate associations were produced by casting process to develop a novel target-specific material. For characterization, tests of water vapor permeability, swelling index, infrared absorption spectroscopy, thermogravimetric analysis, scanning electron microscopy and mechanical analysis were performed. The polysaccharide concentration directly influenced vapor permeability and swelling, increasing the values of the latter up to five times when added in a proportion of 20% (per weight). The individual properties of each polymer were maintained, and chemical interactions were not detected. The films were found to be thermally stable and they had unaltered mechanical properties with the addition of the polysaccharide. The microscopic analysis revealed rugosity that was proportional to pullulan and disorganization of the polymer network at pH 6.8. These results suggest that this novel material has potential for enteric drug release because of synergism between pH and enzyme dependence.
  • Development and validation of a stability indicating HPLC method to determine diltiazem hydrochloride in tablets and compounded capsules Article

    Souza, Mateus Araújo Castro e; Pereira, Carlos Eduardo de Oliveira; Nogueira, Fernando Henrique Andrade; Pianetti, Gerson Antônio

    Abstract in English:

    ABSTRACT A stability indicating HPLC method to determine diltiazem hydrochloride (DTZ) in tablets and compounded capsules was developed and validated according to Brazilian and the International Conference on Harmonization (ICH) guidelines. The separation was carried out on a Purospher Star® C18 (150 x 4.6 mm i.d., 5 µm particle size, Merck Millipore) analytical column. The mobile phase consisted of a 0.05% (v/v) trifluoroacetic acid aqueous solution and a 0.05% trifluoroacetic acid methanolic solution (44:56, v/v). The flow rate was 1.0 mL.min-1 with a run time of 14 minutes. The detection of DTZ and degradation products (DP) was performed at 240 nm, using a diode array detector. The method proved to be linear, precise, accurate, selective, and robust, and was adequate for stability studies and routine quality control analyses of DTZ in tablets and compounded capsules.
  • Spectrophotometric determination of rosuvastatin in pharmaceutical formulations using quinalizarin Article

    Lima, Monica Força; Cassella, Ricardo Jorgensen; Pacheco, Wagner Felippe

    Abstract in English:

    ABSTRACT This work presents the development of a methodology based on the formation of a charge transfer complex between quinalizarin and rosuvastatin, allowing for the spectrophotometric determination of rosuvastatin at 579 nm. The factors involved in the sensitivity of the technique were studied (nature and proportion of the solvent, reaction time, pH of aqueous phase and quinalizarin concentration). The proposed spectrophotometric procedures were validated with respect to linearity, ranges, precision, accuracy, detection and quantification limits. Calibration curves of the formed color products showed good linear relationships over the concentration range of 6-15 mg L-1. The proposed method has been successfully applied, which can be confirmed by interference test (comparison between the standard curves and addition of analyte), method precision (RSD 2.3% to 6 mg L-1), and by accuracy (statistically equivalent results between the proposed method and a chromatographic method of reference).
  • Anti-inflammatory and healing action of oral gel containing borneol monoterpene in chemotherapy-induced mucositis in rats ( Rattus norvegicus ) Article

    Nascimento-Júnior, Braz José do; Brito, Lucas de Souza; Barros, Walquíria Nunes; Gonçalves, Daniela Marques; Matos, Luana de Souza; Nascimento, Cínthia Reyjane Borges; Ribeiro, Luciano Augusto de Araújo; Lima, Ricardo Santana de; Silva-Júnior, René Geraldo Cordeiro; Reis, Sílvio Alan Gonçalves Bomfim; Gonçalves, Talita Mota; Amorim, Elba Lúcia Cavalcanti de

    Abstract in English:

    ABSTRACT The aim of this study was to investigate the effect of gels containing the monoterpene borneol in induced oral mucositis using an animal model. Gels were prepared with borneol at 1.2% and 2.4% (w/w). Oral mucositis was induced by administration of three doses of 5-fluorouracil (30 mg/kg, i.p.) and injury with acetic acid (50%, v/v) soaked in filter paper applied to right cheek mucosa for 60s. Four subgroups comprising 12 animals each were formed. Six animals from each group were sacrificed at days seven and fourteen after oral mucositis induction. Mucous samples were processed and stained with hematoxylin-eosin and Masson’s Trichrome. The semiquantitative evaluation involved observation of inflammatory parameters. ImageJ® software was used in the quantitative evaluation. For statistical analyses, Two-way ANOVA, followed by Tukey’s post-test (p <0.05), were employed. Borneol 2.4% gel proved effective in the treatment of oral mucositis with statistically significant differences between groups for angiogenesis control, inflammatory cell count reduction and percentage neoformed collagen increase. The confirmation of anti-inflammatory and healing action of borneol in oral mucositis in rats renders it a good marker for predicting this activity for plant extracts rich in this substance.
  • Antioxidant and cytotoxic activity of Tecoma stans against lung cancer cell line (A549) Article

    Robinson, Jayachandran Philip; Suriya, Kumaresan; Subbaiya, Ramasamy; Ponmurugan, Ponnusamy

    Abstract in English:

    ABSTRACT Human have been constantly using plants and plant products to overcome many diseases. The antioxidant property of the plant sources is studied to obtain an efficacious drug against cancer. The objectives of the present study is to evaluate the antioxidant and cytotoxic activity of the Tecoma stans extracts against lung cancer cell line in comparison with vincristine drug. The antioxidant activity was studied using the standard DPPH assay and the cytotoxic activity using MTT assay. DPPH assay results show that methanolic extract of T. stans in higher concentration show better antioxidant potential than the standard L-ascorbic acid. They exhibited strong antioxidant potential at 20 µg/mL concentration. The absorbance at 517 nm showed that in the range of 0.201-0.0203 compared to that of absorbance of ascorbic acid at 0.023.Cytotoxic activity was studied using MTT assay which showed that the increase in concentration of extract increases the cell death. At 100µg/mL concentration there is an increased cytotoxic activity, i.e., 99% of cell inhibition. The results of antioxidant and anticancerous activity may be positively correlated.
  • In silico pharmacodynamics, toxicity profile and biological activities of the Saharan medicinal plant Limoniastrum feei Article

    Ammar, Ouahab

    Abstract in English:

    ABSTRACT In-silico study was performed to find the pharmacodynamics, toxicity profiles and biological activities of three phytochemicals isolated from Limoniastrum feei (Plumbagenaceae). Online pharmacokinetic tools were used to estimate the potential of Quercetin, kaempferol-3-O-β-D-glucopyranoside (astragalin) and quercitin-7-O-β-D-glucopyranoside as specific drugs. Then the prediction of potential targets of these compounds were investigated using PharmMapper. Auto-Dock 4.0 software was used to investigate the different interactions of these compounds with the targets predicted earlier. The permeability of quercetin was found within the range stated by Lipinski ׳s rule of five. Hematopoietic prostaglandin (PG) D synthase (HPGDS), farnesyl diphosphate synthetase (FPPS) and the deoxycytidine kinase (DCK) were potential targets for quercetin, astragalin and quercetin 7, respectively. Quercetin showed antiallergic and anti-inflammatory activity, while astragalin and quercetin 7 were predicted to have anticancer activities. The activity of Astragalin appeared to be mediated by FPPS inhibition. The inhibition of DCK was predicted as the anticancer mechanisms of quercetin 7. The compounds showed interesting interactions and satisfactory binding energies when docked into their targets. These compounds are proposed to have activities against a variety of human aliments such as allergy, tumors, muscular dystrophy, and diabetic cataracts.
  • HPLC method development and validation for the estimation of Axitinib in rabbit plasma Article

    Suneetha, Achanta; Donepudi, Sharmila

    Abstract in English:

    ABSTRACT A rapid, sensitive, and accurate high performance liquid chromatography for the determination of Axitinib (AN) in rabbit plasma is developed using crizotinibe as an internal standard (IS). Axitinib is a tyrosine kinase inhibitor, used in the treatment of advanced kidney cancer, which works by slowing or stopping the growth of cancer cells. The chromatographic separation was performed on a Waters 2695, Kromosil (150 mm × 4.6 mm, 5 µm) column using a mobile phase containing buffer (pH 4.6) and acetonitrile in the ratio of 65:35 v/v with a flow rate of1 mL/min. The analyte and internal standard were extracted using liquid-liquid extraction with acetonitrile. The elution was detected by photo diode array detector at 320 nm.The total chromatographic runtime is 10.0 min with a retention time for Axitinib and IS of 5.685, and 3.606 min, respectively. The method was validated over a dynamic linear range of 0.002-0.2µg/mL for Axitinib with a correlation coefficient of r2 0.999.
  • Spray dried aqueous extract of Orthosiphon aristatus Blume (Java tea) Article

    Robaina-Mesa, Malvis; López-Hernández, Oreste Dario; Rodríguez-Chanfrau, Jorge Enrique; Nogueira-Mendoza, Antonio

    Abstract in English:

    ABSTRACT Orthosiphon aristatus (Lamiaceae) is an herb medicinal found mainly in China, Indian and South East Asia. The purpose of this work was to develop a technological process for obtaining dry extract of Orthosiphon aristatus by spray dry. A process for the obtaining of dry extract from aqueous extract of Orthosiphon aristatus was studied. Response Surface Methodology experimental design was applied to evaluate the effects of inlet and outlet air temperature on drying yield (%). Mixture experimental design was applied to evaluate the drying adjuvant - total solids relation. Maltodextrin was evaluated as drying adjuvant. The best results were obtained when applying an inlet temperature of 120 °C and outlet temperature of 80 °C and a drying adjuvant - total solids relation (w/w) of 60:40. Under these conditions it was demonstrated that the process is reproducible scale studied.
  • Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion Article

    Fonseca-Santos, Bruno; Funagoshi, Erica Emi; Oliveira, José Ricardo Soares de; Sacramento, Luis Vitor Silva do; Santos, André Gonzaga dos; Leonardi, Gislaine Ricci; Chorilli, Marlus

    Abstract in English:

    ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.
  • Effect of peracetic acid on biofilms formed by Listeria monocytogenes strains isolated from a Brazilian cheese processing plant Article

    Lee, Sarah Hwa In; Barancelli, Giovana Verginia; Corassin, Carlos Humberto; Rosim, Roice Eliana; Coppa, Carolina Fernanda Sengling Cebin; Oliveira, Carlos Augusto Fernandes de

    Abstract in English:

    ABSTRACT This study aimed to investigate the effect of peracetic acid (PAA, 0.5%) on adherent cells of three strains of Listeria monocytogenes strains belonging to serotypes 4b and 1/2b that had been previously isolated from the environment of a Brazilian cheese plant. The assays were conducted using polystyrene microplates and stainless steel coupons and the adhered cells were treated with PAA for 60, 120 and 180 s. On stainless steel, biofilms were partially inactivated by PAA after 60 s and almost 100% of the cells were damaged within 180 s using epifluorescence microscopy with LIVE/DEAD® staining. On polystyrene microplates, PAA decreased (P<0.05) biofilm biomass produced by the three L. monocytogenes isolates at 60 s, when compared with controls (no PAA treatment). However, PAA did not completely eliminate L. monocytogenes cells on polystyrene microplates (decreasing 1.8-2.5 log cycles after treatment with PAA for 180 s). The correct concentration and contact time of PAA is critical for eliminating biofilms formed by L. monocytogenes on stainless steel surfaces, although further studies are needed for defining efficient PAA treatments to remove adherent cells of this pathogen on plastic polymers.
  • Negative effects of bisphenol A on testicular functions in albino rats and their abolitions with Tribulus terristeris L. Article

    Munir, Bushra; Qadir, Abdul; Tahir, Mohammad

    Abstract in English:

    ABSTRACT This study was conducted to find out the ameliorative properties of Tribulus terristeris L (TT) on BPA induced spermatotoxicity in male albino rats. Mature male albino rats were divided into five groups, Group A was taken as control for comparison group, whereas the other four groups namely B(vehicle control), C (toxic), D (preventive control) and Group E (amelioration group) received distilled water, olive oil, BPA, TT, and (TT + BPA) respectively. Macroscopic results revealed decreased body weight of rats, weight of testes, and the relative tissue weight index (RTWI) in BPA induced group. Hormonal (testosterone) assay results revealed the decreased values of BPA treated group. Microscopic examination of testis of BPA treated rats showed reduction in leydig cells, decreased diameter of seminiferous tubules and low values of Johnsen’s scoring. Histological examination showed discontinuity and irregularity of basement membrane and sloughing of the germinal cell linage. Group E showed the body weights of rats, weight of testes, RTWI, and increased, while reduced level of testosterone, reduced number of Leydig cells, decreased diameter of seminiferous tubules and low values of Johnsen’s scoring were restored near to normal. These results demonstrate that TT might be beneficial in combating the spermatotoxicity, induced by BPA.
  • Cholesterol improves the transfection efficiency of polyallylamine as a non-viral gene delivery vector Article

    Oskuee, Reza Kazemi; Ramezanpour, Mahdieh; Gholami, Leila; Malaekeh-Nikouei, Bizhan

    Abstract in English:

    ABSTRACT Cationic polymers such as polyallylamine (PAA) having primary amino groups are poor transfection agents and possess a high cytotoxicity index when used without any chemical modification. In this study, PAA was modified with cholesterol in order to improve transfection efficiency and to reduce cytotoxicity. PAA polymers with molecular weights of 15 and 65 kDa were selected and grafted with cholesterol at percentages of 5, 10, 15, 30, and 50. After purification, the efficacy of the synthetic vectors was evaluated in terms of DNA condensation using the ethidium bromide test, buffering capacity, particle size, zeta potential, transfection efficiency, and cytotoxicity assay in Neuro2A cell lines. According to the ethidium bromide test, these vectors can condense DNA at moderate and high carrier to plasmid (C/P) ratios. The buffering capacity of the prepared vector in both molecular weights was less than unmodified PAA. Particle size measurements demonstrated that modified PAAs were able to form nanoparticles ranging in size from 125 to 530 nm. The vectors based on PAA 15 kDa demonstrated a better transfection efficiency than the vectors made of PAA 65 kDa. Cytotoxicity studies showed that toxicity of all vectors was less than PAA. Some cholesterol modified polymers composed of PAA (15 kDa) were suitable vectors for gene delivery with low cytotoxicity.
  • Measurement uncertainty of dissolution test of acetaminophen immediate release tablets using Monte Carlo simulations Article

    Romero, Daniel Cancelli; Lourenço, Felipe Rebello

    Abstract in English:

    ABSTRACT Analytical results are widely used to assess batch-by-batch conformity, pharmaceutical equivalence, as well as in the development of drug products. Despite this, few papers describing the measurement uncertainty estimation associated with these results were found in the literature. Here, we described a simple procedure used for estimating measurement uncertainty associated with the dissolution test of acetaminophen tablets. A fractionate factorial design was used to define a mathematical model that explains the amount of acetaminophen dissolved (%) as a function of time of dissolution (from 20 to 40 minutes), volume of dissolution media (from 800 to 1000 mL), pH of dissolution media (from 2.0 to 6.8), and rotation speed (from 40 to 60 rpm). Using Monte Carlo simulations, we estimated measurement uncertainty for dissolution test of acetaminophen tablets (95.2 ± 1.0%), with a 95% confidence level. Rotation speed was the most important source of uncertainty, contributing about 96.2% of overall uncertainty. Finally, it is important to note that the uncertainty calculated in this paper reflects the expected uncertainty to the dissolution test, and does not consider variations in the content of acetaminophen.
  • Aggravation of cyclophosphamide-induced reproductive toxicity in mice by aqueous extract of Aegle marmelos (L.) Article

    Singh, Sangita; Mishra, Awadhesh Kumar; Lata, Swarn; Tiwari, Kavindra Nath

    Abstract in English:

    ABSTRACT Aegle marmelos (L.) (Rutaceae) commonly known as bael is an important medicinal fruit tree. The present study focused on the effects of aqueous extract of Aegle marmelos (AEAM) on the testis and sperm characteristics induced by cyclophosphamide (CPA) in mice. Thirty six adult Parke’s strain mice were divided into six groups: group I given only distilled water (control); group II administered with AEAM alone once in a week for five weeks; group III administered with CPA (200 mg/kg b.w., intraperitoneally) once in a week for five weeks and group IV-VI CPA along with AEAM (400, 500 and 600 mg/kg b.w., orally). CPA was found to reduce gonadosomatic index (GSI), sperm counts, motility, viability, antioxidant activities and induced histopathological changes of testis. In the group administered AEAM with CPA an exacerbation of sperm count, motility and viability of the cauda epididymis, GSI, antioxidant activities and architecture of testis was observed. The results suggest that the administration of AEAM may aggravate CPA-induced reproductive toxicity. It may be helpful in preparation of natural male contraceptives.
  • The in vivo effect of L-arginine on skin elasticity in mice Article

    Souza, Ádria do Prado Barros de; Oliveira, Marina Miranda Rocha de; Andrade, Rafael Rocha de; Amorim, Rivadávio Fernandes Batista de; Bocca, Anamélia Lonrezetti; Borin, Maria de Fátima

    Abstract in English:

    ABSTRACT The human skin aging process is a complex mechanism that can be induced both by intrinsic and extrinsic factors. Observations include a decrease in the biosynthetic and proliferative capacity of cells, increased expression of matrix metalloproteinases, reduction in collagen type I expression, and the progressive disappearance of elastic tissue in the papillary dermis. L-arginine, the substrate of nitric oxide synthesis, is involved in angiogenesis and cell proliferation, as well as an indirect precursor of collagen synthesis via the proline pathway. The aim of this study was to examine the tensile strength, histology, and immunohistochemistry of female and male mice skin receiving different concentrations of topically applied L-arginine, in order to evaluate the possibility of using L-arginine as an active cosmetic ingredient in antiaging products. The results suggest that the application of L-arginine improves the mechanical resistance of skin from older female mice (20 weeks old) and promotes the formation of a larger amount of collagen and elastic fibers in the skin when applied at a concentration of 15%.
  • Cost-effectiveness of insulin analogs from the perspective of the Brazilian public health system Article

    Cazarim, Maurílio de Souza; Rodrigues, João Paulo Vilela; Cruz-Cazarim, Estael Luzia Coelho da; Ayres, Lorena Rocha; Pereira, Leonardo Régis Leira

    Abstract in English:

    ABSTRACT Human insulin is provided by the Brazilian Public Health System (BPHS) for the treatment of diabetes, however, legal proceedings to acquire insulin analogs have burdened the BPHS health system. The aim of this study was to perform a cost-effectiveness analysis to compare insulin analogs and human insulins. This is a pharmacoeconomic study of cost-effectiveness. The direct medical cost related to insulin extracted from the Ministry of Health drug price list was considered. The clinical results, i.e. reduction in glycated hemoglobin (HbA1c), were extracted by meta-analysis. Different scenarios were structured to measure the uncertainties regarding the costs and reduction in HbA1c. Decision tree was developed for sensitivity of Incremental Cost Effectiveness Ratio (ICER). A total of fifteen scenarios were structured. Given the best-case scenario for the insulin analogs, the insulins aspart, lispro, glargine and detemir showed an ICER of R$ 1,768.59; R$ 3,308.54; R$ 11,718.75 and R$ 2,685.22, respectively. In all scenarios in which the minimum effectiveness was proposed, lispro, glargine and detemir were dominant strategies. Sensitivity analysis showed that the aspart had R$ 3,066.98 [95 % CI: 2339.22; 4418.53] and detemir had R$ 6,163.97 [95% CI: 3919.29; 11401.57] for incremental costs. We concluded there was evidence that the insulin aspart is the most cost-effective.
  • Effects of granule particle size and lubricant concentration on tablet hardness containing large concentration of polymers Article

    Rajani, Chauhan; Kumar, Dewangan Devendra; Jaya, Dwivedi; Kumar, Jha Arvind

    Abstract in English:

    ABSTRACT The objective of this research work is to demonstrate the impact of granule size and lubricant concentration on the hardness of tablets in formulations containing higher concentration of polymers and to resolve the hardness issue during compression process. The work involves optimization of a milling process for size reduction of granules and blending process to achieve tablets of good hardness on compression. To optimize the granule size, different sized co-mill screens were used. The different concentration of lubricant were studied on different sized granules to check the effect on hardness of tablets and to obtained the desired hardness of tablets. Compression of lubricated blend in various concentration was performed using the gravity feeder and force feeder separately to check the impact on the over lubrication effect. This ultimately leads to less hardness tablets. Lubricated blends were evaluated by performing the Bulk Density, Tapped Density, Hausner ratio and compressibility index tests. Tablets were evaluated for the physical characteristics like weight variation, hardness, thickness and dissolution. It has been conclude that on using the optimum granules size and lubricant concentration in formulation, all the downstream problems can be resolved and this in turn helps in compression of tablets and also provides the good hardness to the tablets.
  • 4-Nerolidylcatechol induces autophagy in human glioblastoma cells Article

    Massaro, Renato Ramos; Brohem, Carla Abdo; Almeida, Rebeca Leite de; Rivelli, Diogo Pineda; Miyake, Juliano Andreoli; Colquhoun, Alison; Barros, Silvia Berlanga de Moraes; Maria-Engler, Silvya Stuchi

    Abstract in English:

    ABSTRACT Gliomas account for the majority of primary malignant brain tumors and present invasive behavior into adjacent healthy tissue. While 4-NC had previously shown to induce apoptotic cell death in a melanoma model, for the glioma model described in this paper 4-NC is cytotoxic for the cells with the induction of the autophagic pathway. Trypan blue exclusion assay showed that 4-NC was cytotoxic in a dose-dependent manner for A172 and T98G cell lines. IC10 and IC50 values were at 32 µM and 41 µM for A172 and T98G respectively. Inhibition of cell proliferation was observed by total cell counts and by cell cycle analysis by flow cytometry, with cell cycle arrest of A172 and T98G cell lines respectively in the G1/G0 and S phases of the cell cycle. 4-NC induced up-regulation of autophagic pathways, as shown by immunoblotting for LC3-I/II, Real-Time PCR for ATG-7 and Beclin-1 genes, and by fluorescence microscopy observation of autophagic vacuoles in cells transfected with GFP-LC3 and electron microscopy. Glioma cells concomitantly treated with 4-NC and 3-MA, an inhibitor of the autophagic process, are more sensible to cell death, suggesting that autophagy protects the cells from the action of 4-NC.
  • Total flavonoids from Ampelopsis megalophylla suppress proliferation of vascular smooth muscle cells in vivo and in vitro Article

    Qiu, Zhenpeng; Zhou, Junxuan; Hu, Junjie; Wu, Yong; Zheng, Guohua

    Abstract in English:

    ABSTRACT Various benefits of flavonoids for ameliorating cardiovascular diseases have been demonstrated. However, the lowering effects on blood pressure caused by antiproliferative potentials of flavonoids in vascular smooth muscle cells are rare. In this study, the antihypertensive effects of total flavonoids from Ampelopsis megalophylla were investigated. The dynamic pressure values and the rate of media thickness versus lumen diameter were measured by the tail-cuff system and H&E staining in vivo, respectively. The mRNA expressions of ACE, Ang II, eNOS, c-Myc, cyclin D1 and p27Kip1 in thoracic aorta or A7r5 cells were measured by qPCR, respectively. The protein expressions of c-Myc, Cyclin D1, p27Kip1 and β-catenin in tissues or A7r5 cells were measured by Western blot assay. Total flavonoids of A. megalophylla (TFAM) reduced the expressions of ACE and Ang II, and elevated the content of eNOS in thoracic aorta cells of SHRs. Furthermore, TFAM decreased the mRNA and protein expressions of c-Myc and cyclin D1 by repressing the Wnt/β-catenin-mediated TCF/LEF transcriptional activation both in vivo and in vitro, which is synergetic with the up-regulation of p27Kip1 expression. Our study provided evidence for developing flavonoids from A. megalophylla as herbal supplements to prevent against cardiovascular diseases by suppressing vascular remodeling.
  • Cost-consequence analysis of Pharmaceutical Care program for systemic arterial hypertension in the public health system in Brazil Article

    Cazarim, Maurílio de Souza; Nunes, Altacílio Aparecido; Pereira, Leonardo Régis Leira

    Abstract in English:

    ABSTRACT In Brazil, 80% of hypertensive patients have no blood pressure controlled, this fact has caused severe financial consequences for the public health system (PHS) and the Pharmaceutical Care (PC) has emerged as an effective alternative. The aim of this study was to analyze the costs and outcomes of systemic arterial hypertension (SAH) for conventional assistance compared to assistance with PC in the PHS. This is a pharmacoeconomic study with cost-consequence analysis nested to clinical trial. Hypertensives patients were followed-up from 2006 to 2012. During 2009 they were assisted by the PC program in Ribeirão Preto-SP, Brazil. Clinical indicators, systolic and diastolic blood pressure (SBP and DBP), triglycerides, total cholesterol (TC) and its fractions and healthcare indicators, consumption of antihypertensive medication and consultations were analyzed. Costs were listed as direct medical and direct non-medical. The average cost of conventional care for 104 patients followed-up was US$ 198.97, in the PC period and after discharge was US$ 407.91 and US$ 214.96 patient/year. After discharge of patients from PC there was reduction of SBP, DBP, TC and cardiovascular risk, 9.4 mmHg, 4.6 mmHg, 12.0 mg/dL, and 23% [p<0.005], respectively. The PC program optimized clinical and healthcare indicators and impacted in the SAH costs for the PHS.
  • Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth Article

    Silva, Aline Teixeira Maciel e; Magalhães, Cássia Gonçalves; Duarte, Lucienir Pains; Mussel, Wagner da Nova; Ruiz, Ana Lucia Tasca Gois; Shiozawa, Larissa; Carvalho, João Ernesto de; Trindade, Izabel Cristina; Vieira, Sidney Augusto

    Abstract in English:

    ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3’,4’-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.
  • Use of unlicensed and off-label drugs in neonates in a Brazilian university hospital Article

    Gonçalves, Adriana Cristina de Souza; Reis, Adriano Max Moreira; Marçal, Ana Carolina Gusmão; Bouzada, Maria Cândida Ferrarez

    Abstract in English:

    ABSTRACT This study was designed to investigate the use of off-label and unlicensed drugs in a Neonatal Care Unit (NCU) and to compare the frequency of use of off-label drugs according to the drug regulatory agencies in Brazil (Agência Nacional de Vigilância Sanitária-ANVISA) and the United States Food and Drug Administration (FDA). A prospective observational study was carried out in the NCU. Prescriptions were classified as off-label and unlicensed using both ANVISA and FDA criteria. A total of 157 newborns and 1187 prescriptions were analyzed. The most prescribed drug was fentanyl (9.3%), followed by multivitamin (8.4%) and gentamicin (7.9%). According to ANVISA criteria, there were 665 (56.0%) off-label prescriptions and 86 (7.2%) unlicensed prescriptions and 95.5% of newborns received at least one drug off-label. By contrast, according to FDA criteria, there were 592 (49.9%) off-label prescriptions and 84 (7.1%) unlicensed prescriptions, and 72.0% of newborns received at least one drug off-label. The off-label use of drugs registered by ANVISA differed significantly from that of drugs registered by the FDA. There was a high frequency of off-label and unlicensed drug use in the investigated NCU, and there was an inverse relationship between off-label and unlicensed usage and the gestational age of the newborns.
  • Chemical compositions and antioxidant activity of Heracleum persicum essential oil Article

    Gharachorloo, Maryam; Honarvar, Masoud; Mardani, Shima

    Abstract in English:

    ABSTRACT In this study essential oil of the aerial parts of Heracleum persicum a spice widely used in Iran was isolated by conventional hydrodistillation (HD) and microwave-assisted hydrodistillation (MAHD) techniques. The extraction yield was determined and the chemical compositions of essential oils were identified by the application of gas chromatography/mass spectrometry (GC/MS). The antioxidant activity was determined by two different methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and oven test methods. Although the main compounds of essential oils by the both extraction methods were similar, the essential oil extracted by HD with lower extraction efficiency showed more diverse compounds. The evaluation of antioxidant activity of the essential oil measured by delay in sunflower oil oxidation indicated that the antioxidant activity was dependent on the concentration which increased when higher concentrations of the essential oils were applied. The results of DPPH radical assay also indicated that the percentage of inhibition increased with increasing of essential oil concentration and IC50 value for essential oil extracted by MAHD method was obtained 1.25 mg/mL. Therefore the Heracleum persicum essential oil might be recommended for use as a flavoring agent and a source of natural antioxidants in functional foods, formulation of the supplements and in medicinal due to numerous pharmacological activities.
  • Oxidative stress and histopathologic biomarkers of exposure to bisphenol-A in the freshwater fish, Ctenopharyngodon idella Article

    Faheem, Mehwish; Lone, Khalid Parvez

    Abstract in English:

    ABSTRACT Bisphenol-A (BPA) belongs to the family of endocrine disrupting chemicals (EDCs) and it is used in the production of polycarbonate plastic and epoxy resins. The reproductive toxicity of BPA is well documented but it also exerts its toxic effects through multiple pathways especially by inducing a state of oxidative stress and causing damage to the vital organs. In the present study, histopathologic and oxidative damage caused by BPA in liver and kidneys of fresh water cyprinid, Ctenopharyngodon idella was evaluated. LC50 of BPA for Ctenopharyngodon idella was determined by probit regression analysis. Fish were exposed to a sublethal concentration of BPA i.e. 3.2 ppm (1/2 LC50) for 14 days. Histologic studies revealed that BPA caused degenerative changes in liver and kidneys and exposure of sublethal concentration of BPA caused oxidative damage in both organs. Lipid peroxidation significantly increased in liver and kidneys of treated group. Catalase activity and reduced glutathione content significantly decreased in the group exposed to BPA compared to control and glutathione-S-transferase activity increased significantly in both organs exposed to the sublethal concentration of BPA. From this study it is concluded that BPA caused toxic effects in fish species by changing oxidative balance and damaging the vital organs.
  • The impacts of Elaeagnus umbellata Thunb. leaf and fruit aqueous extracts on mice hepatic, extrahepatic antioxidant and drug metabolizing enzymes related structures Article

    Ozen, Tevfik; Yildirim, Kemal; Toka, Mehmet

    Abstract in English:

    ABSTRACT In this work, the potential chemopreventive activities of Elaeagnus umbellata fruit aqueous (EUFA) and leaf aqueous (EULA) extracts focusing on the modulatory influence of xenobiotic metabolizing enzymes (XMEs), antioxidant enzymes, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH) activity, lipid peroxidation (LP), sulfhydryl groups were investigated in the hepatic and extrahepatic organs of Swiss albino mice (50 and 100 mg/kg body wt given orally for 14 days) and compared with BHA (0.75 % in diet). The modulatory and chemopreventive properties of two different doses EUFA and EULA were observed for cytochrome P450, cytochrome b5, sulfhydryl groups, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, 7-ethoxyresorufin-deethylase and N,N-dimethylaniline N-oxidase activities in the liver and compared with BHA as a standard. The activities of glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a significant increase in the kidney, forestomach, heart and brain at both doses of EUFA and EULA. The results of EULA-treated groups were found a notable increase in LDH, G6PD, 6PGD, GST and DTD activities. Superoxide dismutase level in liver, kidney and heart exhibited a significant increase at both doses of EULA. Glutathione reductase activity was a remarkable level at high dose of EUFA in liver, kidney and EULA in kidney. Both doses of EUFA were effective in inducing glutathione peroxidase activitiy in heart. The levels of LP at low and high doses of EULA-treated and EUFA-treated were effective in liver and kidney, respectively. The present results demonstrate that significant effects in the level of XMEs and antioxidant enzymes of EUFA and EULA are remarkable for modulating roles and natural chemoprevention properties and therefore is considered for a valuable natural source.
  • Association between kidney function and Framingham risk score in an admixed population of Brazil Article

    Costa, Brunna Soares Rodrigues; Freitas, Erika Paula Silva; Cruz, Marina Sampaio; Duarte, Victor Hugo Rezende; Silva, Ananília Medeiros Gomes da; Santos, Isabelle Cristina Clemente dos; Santos, Jéssica Cavalcante dos; Rezende, Adriana Augusto; Sena-Evangelista, Karine Cavalcanti Maurício; Silbiger, Vivian Nogueira

    Abstract in English:

    ABSTRACT Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk development. However, the mechanisms of reduced kidney function with CVD risk are unclear. This study aimed to investigate the association between kidney function and Framingham risk score (FRS) in participants with traditional cardiovascular risk factors and normal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m² in an admixed population of Brazil. The participants were divided into three groups according to FRS: low risk group with 0% to <10%, moderate risk group with ≥10% to 20% and high risk group with >20%. The eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Data from participants were collected by questionnaire, and blood and urine samples were collected to analyze biochemical markers. A total of 214 subjects aged 53±10 years old was collected. There were 77 individuals in low risk group, 59 in moderate risk group and 78 in high-risk group. Mean eGFRCKD-EPI was 89.39±15.05 mL/min/1.73 m² and 90.74±16.17 mL/min/1.73 m2 when race adjustment. The results indicated that there is an increasing the cardiovascular risk with a decreased of eGFR, conforming to a significant inverse correlation observed between eGFR and FRS with Spearman correlation (R²=-0.256, p<0.001; R²=-0.224, p=0.001, when adjusted for race). There was a statistically significant difference in eGFRCKD-EPI (p<0.001) and eGFRCKD-EPI with race adjustment (p=0.002) among risk groups. The data suggests that the reduction eGFR is associated with elevated FRS among Brazilian adults without CKD. Furthermore, the results suggest that race adjustment it’s not necessary in Brazilian population.
  • Exploring the natural chemiome to target interleukin-6 receptor (IL-6R) cytokines: an atomic scale investigation for novel rheumatoid arthritis drug discovery Article

    Chen, Qiujian; Niu, Xiaohui; Li, Nana

    Abstract in English:

    ABSTRACT Natural compounds are a gold mine for treating rheumatoid arthritis (RA). The etiology of this disease is linked to inflammation, where cytokines play an important role. Strategies have been drafted for targeting cytokines as a therapeutic option in patients with RA. Inhibiting cytokines with natural compounds has become a major focus for the development of drugs to treat RA. Here, a structure-based drug design approach was employed to identify novel leads to target the interleukin 6 receptor (IL-6R). A total of 48,531 compounds of natural origin were screened. Two of these compounds were shortlisted for molecular docking simulation and tested for inhibiting gp130 dimerization in human macrophages. The results show that Lead5 (CID5329098) significantly inhibited the release of gp130 in a dose-dependent manner, similar to the inhibitory effect of LMT-28 (p<0.005). This study provides an atomic scale outcome of a single natural compound that can be developed into a RA drug.
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
E-mail: bjps@usp.br