Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. / Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão.

BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Effects of ADIPOQ and NOS3 SNPs/haplotypes on blood pressure control in patients with adherence to antihypertensive therapy.

Aim: We examined whether ADIPOQ (rs266729 and rs1501299) and NOS3 (rs3918226 and rs1799983) SNPs or the haplotypes formed by them, affect blood pressure (BP) control in 196 patients with adherence to antihypertensive therapy grouped into controlled (BP <140/90 mmHg) and uncontrolled (BP ≥140/90 mmHg) hypertension. Materials & methods: The average of the three most recent BP measurements was retrieved from the patients' electronic medical records. Adherence to antihypertensive therapy was evaluated using the Morisky-Green test. Haplotype frequencies were estimated using Haplo.stats. Multiple logistic/linear regression analyses were adjusted for the covariates ethnicity, dyslipidemia, obesity, cardiovascular disease and uric acid. Results: ADIPOQ rs266729 genotypes CG (additive model) and CG+GG (dominant model) were associated with uncontrolled hypertension and CG was associated with higher systolic BP and mean arterial pressure (p < 0.05). ADIPOQ haplotypes 'GT' and 'GG' were associated with uncontrolled hypertension and 'GT' was associated with higher diastolic BP and mean arterial pressure (p < 0.05). Conclusion: ADIPOQ SNPs and haplotypes affect BP control in hypertensive patients undergoing treatment.

Anti-Zika Virus Activity and Isolation of Flavonoids from Ethanol Extracts of Curatella americana L. Leaves.

The ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian Cerrado, whose ethanolic extract showed significant in vitro anti-Zika virus activity by the MTT colorimetric method. Currently, there is no drug in clinical use specifically for the treatment of this virus; therefore, in this work, the antiviral and cytotoxic properties of the ethanolic extract, fractions, and compounds were evaluated. The ethanolic extract of the leaves showed no cytotoxicity for the human MRC-5 cell and was moderately cytotoxic for the Vero cell (CC50 161.5 ± 2.01 µg/mL). This extract inhibited the Zika virus multiplication cycle with an EC50 of 85.2 ± 1.65 µg/mL. This extract was fractionated using the liquid-liquid partition technique, and the ethyl acetate fraction showed significant activity against the Zika virus with an EC50 of 40.7 ± 2.33 µg/mL. From the ethyl acetate fraction, the flavonoids quercetin-3-O-hexosylgallate (1), quercetin-3-O-glucoside (2), and quercetin (5) were isolated, and in addition to these compounds, a mixture of quercetin-3-O-rhamnoside (3) and quercetin-3-O-arabinoside (4) was also obtained. The isolated compounds quercetin and quercetin-3-O-hexosylgallate inhibited the viral cytopathic effect at an EC50 of 18.6 ± 2.8 and 152.8 ± 2.0, respectively. Additionally, analyses by liquid chromatography coupled to a mass spectrometer allowed the identification of another 24 minor phenolic constituents present in the ethanolic extract and in the ethyl acetate fraction of this species.

Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients.

INTRODUCTION: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. OBJECTIVE: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. METHOD: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. RESULTS: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. CONCLUSION: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.

Evaluation of Anti-Candida albicans Activity and Release of Ketoconazole in PMMA-G-PEG 4000 Films.

Modified release systems depend on the selection of an appropriate agent capable of controlling the release of the drug, sustaining the therapeutic action over time, and/or releasing the drug at the level of a particular tissue or target organ. Polyethylene glycol 4000 (PEG 4000) is commonly employed in drug release formulations while polymethyl methacrylate (PMMA) is non-toxic and has a good solubility in organic solvents. This study aimed at the incorporation of ketoconazole in PMMA-g-PEG 4000 and its derivatives, thus evaluating its release profile and anti-Candida albicans and cytotoxic activities. Ketoconazole was characterized and incorporated into the copolymers. The ketoconazole incorporated in the copolymer and its derivatives showed an immediate release profile. All copolymers with ketoconazole showed activity against Candida albicans and were non-toxic to human cells in the entire concentration tested.

Additive effects of resveratrol and doxorubicin on bladder cancer cells.

The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.

Bacterial vaginosis: prevalence, risk profile and association with sexually transmitted infections / Vaginose bacteriana: prevalência, perfil de risco e associação com infecções sexualmente transmissíveis / Vaginosis bacteriana: prevalencia, perfil de riesgo y asociación con infecciones de transmisión sexual

Background and Objectives: Bacterial vaginosis (BV) is the most common cause of vaginal discharge in the world. The study aimed to estimate the prevalence and to identify risk factors associated with bacterial vaginosis. Methods: A cross-sectional study was conducted in Ouro Preto, Brazil, between February and December 2017. Three hundred and forty-one women aged 18 years or older, users of the Brazilian Unified Health System, participated in this study. Women who used oral or topical antibiotics in the four weeks prior to the sample collection and women who had undergone a total hysterectomy were excluded from the study. After signing the Informed Consent Form and filling out a questionnaire containing sociodemographic, behavioral and sexual data, the participants were directed to the collection room, where the nurse collected the samples for the preventive examination of the cervix and also two vaginal swabs. Vaginal swabs and cervical samples were analyzed for cytological abnormalities and BV using Gram staining and cytology. Pathogens causing sexually transmitted infections (STIs) were identified by Polymerase Chain Reaction (PCR). For the analysis of the data, statistical package STATA version 10.0 was used. This study was approved by the Research Ethics Committee of the Federal University of Ouro Preto (UFOP). Results: During the study, 341 women were evaluated. The prevalence of BV using Gram staining (32.5% [CI95% 27.7-37.7%]) and cytology (27.7% [CI95% 23.032.8%]) was similar, however, the sensitivity of cytology was lower (77.8%). Risk factors associated with BV were smoking (IRR 1.5 [CI95%: 1.1  2.1]), use of an intrauterine device (IRR 2.8 [CI95%: 1.2 - 6.5]), and past medical history of BV (IRR 1.5 [CI95%: 1.1 - 2.1]). Correlation between the presence of BV and Trichomonas vaginalis (TV) infection (r=0.24) was observed. Conclusion: The prevalence of BV was affected by life habits and was prevalent in women with TV. Thus, behavioral and social prevention approaches to women with diverse risk profiles may help mitigate TV/BV prevalence and recurrence of BV.(AU)

Contexte et objectifs: La vaginose bactérienne (VB) est la cause la plus fréquente de pertes vaginales dans le monde. Le but de cette étude était d'évaluer la prévalence et les facteurs associés à la vaginose bactérienne. Méthodes: Il s'agit d'une approche descriptive, transversale et quantitative réalisée à Ouro Preto, Minas Gerais, Brésil, entre février et décembre 2017. 341 femmes ont participé à cette étude, âgées de 18 ans ou plus, utilisatrices du Système de santé unifié. Les femmes ayant utilisé des antibiotiques oraux ou topiques dans les quatre semaines précédant le prélèvement et les femmes ayant subi une hystérectomie totale ont été exclues de l'étude. Après avoir signé le formulaire de consentement éclairé et rempli un questionnaire contenant des données sociodémographiques, comportementales et sexuelles, les participants ont été dirigés vers la salle de collecte, où l'infirmière a prélevé les échantillons pour l'examen préventif du col de l'utérus. et aussi deux écouvillons vaginaux. Les échantillons de frottis vaginaux et cervicaux ont été analysés pour les anomalies cytologiques et VB en utilisant la coloration de Gram et la cytologie. Les agents pathogènes causant des infections sexuellement transmissibles (IST) ont été identifiés par réaction en chaîne par polymérase. Pour l'analyse des données, le progiciel statistique STATA version 10.0 a été utilisé. Cette étude a été approuvée par le Comité d'éthique de la recherche de l'Université fédérale d'Ouro Preto (UFOP). Résultats: Au cours de l'étude, 341 femmes ont été évaluées. La prévalence de la VB avec coloration de Gram (32,5% [IC 95% 27,7 - 37,7%]) et de la cytologie (27,7% [IC 95% 23,0 - 32,8%]) était similaire, cependant la sensibilité cytologique était plus faible (77,8%). Les facteurs de risque associés à la VB étaient le tabagisme (IRR 1,5 [IC 95%: 1,1 - 2,1]), l'utilisation d'un dispositif intra-utérin (IRR 2,8 [IC 95%: 1,2 - 6,5] ) et antécédents médicaux de VB (IRR 1,5 [IC 95%: 1,1 - 2,1]). Il y avait une corrélation entre la présence d'une infection à VB et Trichomonas vaginalis (TV) (r = 0,24). Conclusion: La prévalence de la VB était affectée par le mode de vie et l'infection TV. Ainsi, les approches de prévention comportementale et sociale pour les femmes présentant des profils de risque différents peuvent aider à atténuer la prévalence de la TV / VB et la récurrence de la VB.(AU)

Justificativa e Objetivos: A vaginose bacteriana (VB) é a causa mais comum de corrimento vaginal no mundo. O objetivo desse estudo foi avaliar a prevalência e os fatores associados à vaginose bacteriana. Métodos: Trata-se de um descritivo, de forma transversal e abordagem quantitativa realizado em Ouro Preto, Minas Gerais, Brasil, entre fevereiro a dezembro de 2017. Participaram desse estudo 341 mulheres com idade igual ou superior a 18 anos, usuárias do Sistema Único de Saúde (SUS). Mulheres que usaram antibióticos orais ou tópicos nas quatro semanas anteriores à coleta e mulheres que haviam sido submetidas a uma histerectomia total foram excluídas do estudo. Após a assinatura do Termo de Consentimento Livre e Esclarecido e preenchimento de questionário contendo dados sócio-demográfico, comportamental e sexual, as participantes foram encaminhadas para a sala de coleta, onde a enfermeira realizou a coleta das amostras para o exame preventivo do colo do útero e também de dois swabs vaginais. As amostras de esfregaço vaginal e cervical foram analisadas quanto às anormalidades citológicas e VB usando coloração de Gram e citologia. Patógenos causadores de infecções sexualmente transmissíveis (ISTs) foram identificados por Reação em Cadeia da Polimerase (PCR). Para a análise dos dados foi utilizado o pacote estatístico STATA versão 10.0. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de Ouro Preto (UFOP). Resultados: Durante o estudo, 341 mulheres foram avaliadas. A prevalência de VB com coloração de Gram (32,5% [IC95% 27,7 - 37,7%]) e citologia (27,7% [IC95% 23,0 - 32,8%]) foi semelhante, porém a sensibilidade da citologia foi menor (77,8%). Os fatores de risco associados ao VB foram tabagismo (IRR 1,5 [IC95%: 1,1 - 2,1]), uso de dispositivo intrauterino (IRR 2,8 [IC 95%: 1,2 - 6,5]) e história médica pregressa de VB (IRR 1,5 [IC95%: 1,1 - 2.1]). Observou-se correlação entre a presença de infecção por VB e Trichomonas vaginalis (TV) (r = 0,24). Conclusão: A prevalência de VB foi afetada por hábitos de vida e infecção por TV. Assim, abordagens de prevenção comportamental e social para mulheres com diversos perfis de risco podem ajudar a mitigar a prevalência de TV / VB e recorrência de VB.(AU)

Melaleuca leucadendra Essential Oil Promotes Loss of Cell Membrane and Wall Integrity and Inhibits Bacterial Growth: An In Silico and In Vitro Approach.

Essential oils are potential antimicrobial agents and can be used as active ingredients in the pharmaceutical, food and cosmetics industries. This work intends to evaluate the antibacterial activity and design a strategy for the proposition of the mechanism of action of Melaleuca leucadendra essential oil. Optimum concentration of the bacteria and the phase where they had the highest pathogenic activity were determined. Results show that for each microorganism it is necessary to use a different concentration at the time of adjusting the initial inoculum, and that the time to achieve exponential growth phase varies from one to the other. M. leucadendra essential oil demonstrated in vitro antimicrobial properties. This oil was chemically characterized and the main compounds were evaluated by their mechanism of antibacterial action based on structure-activity analysis. The mechanism is related to the increase of bacteria cell membrane permeability. This indication was confirmed by flow cytometry and transmission electronic microscopy. Thus, in silico analysis is an important tool in the search for new antimicrobial agents and these results showed that M. leucadendra essential oil may be useful on the development of new chemotherapies or food preservation systems.

Herbal medicines to the treatment of skin and soft tissue infections: advantages of the multi-targets action.

The research for new treatments of skin and soft tissue infections (SSTIs) is important due to their high prevalence and number of hospitalizations. The purpose of this review is to address the pathophysiology of SSTIs to highlight the advantages of herbal medicines to their treatment, showing examples of species and compounds with multi-targets action. SSTIs have a complex physiopathology involving the microorganism, as well as inflammation and difficult healing. Therefore, antimicrobial, anti-inflammatory, antioxidant and healing activities are an approach possible for their treatment. Herbal medicines have a wide diversity of biological compounds, mainly phenolic compounds that may act on different targets and also have synergism between them. Therefore, a single medicine may have the four key activities that allied allow eliminating the infection, control the inflammation process and accelerating the healing process, preventing complications with chronic infections.

Antibacterial substances from leaves of Protium spruceanum (Burseraceae): in vitro and in silico evaluation

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

Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

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

Nanostructured Systems Improve the Antimicrobial Potential of the Essential Oil from Cymbopogon densiflorus Leaves.

The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate their antimicrobial activity. The essential oil was isolated by hydrodistillation from leaves and analyzed by GC-MS. The main constituents were found to be trans-p-mentha-2,8-dien-1-ol, cis-p-mentha-2,8-dien-1-ol, trans-p-mentha-1(7),8-dien-2-ol, cis-piperitol, and cis-p-mentha-1(7),8-dien-2-ol. In silico prediction analysis suggested that this oil possesses antimicrobial potential and the main mechanism of action might be the peptidoglycan glycosyltransferase inhibition. Nanoemulsions were prepared by the phase inversion method, and liposomes were made by the film hydration method. Qualitative evaluation of the antimicrobial activity was performed by the diffusion disk assay with 24 microorganisms; all of them were found to be sensitive to the essential oil. Subsequently, this property was quantified by the serial microdilution technique, where the nanoformulations demonstrated improved activity in comparison with the free oil. Bactericidal action was tested by the propidium iodide method, which revealed that free essential oil and nanoemulsion increased cytoplasmic membrane permeability, while no difference was observed between negative control and liposome. These results were confirmed by images obtained using transmission electron microscopy. This study has shown an optimization in the antimicrobial activity of C. densiflorus essential oil by a nanoemulsion and a liposomal formulation of the active substances.