Descoberta de novos fármacos anti-tumorais e anti-bacterianos de extratos vegetais brasileiros através de screening em larga escala

Plants have played a significant role in the treatment of cancer and infectious diseases for the last four decades. The discovery and introduction to market of paclitaxel, the vinca alkaloids, etoposide, and many antibacterial drugs support drug discovery programs based on natural products. Natural products have been rediscovered as important tools for drug development despite advances in combinatorial chemistry, due to the complex molecular structures able to interact with mammalian cell targets. The Brazilian flora, the most diverse in the world, has become an interesting spot to prospect for new chemical leads or hits due to its species diversity and associated chemical richness. Screening programs have been established in Brazil as a strategy to identify potentially active substances. High throughput screening techniques allow for the analysis of large numbers of extracts in a relatively short period of time, and can be considered one of the most efficient ways of finding new leads from natural products. An updated review of the current status of the biological screening program is presented and recent results from new antitumoral and antibacterial chemical leads are discussed.Plantas são uma importante fonte de novos protótipos há pelo menos quatro décadas. A descoberta e introdução no mercado de paclitaxel, dos alcalóides da vinca, etoposídeo e muitos agentes antibacterianos têm servido de apoio ao desenvolvimento de programas de descobrimento de novos fármacos baseados em produtos naturais. Produtos naturais foram recentemente redescobertos como importante ferramenta na descoberta de novos fármacos devido às estruturas moleculares complexas capazes de interagir com alvos em células de mamíferos. A flora brasileira, a mais rica do mundo, tornou-se um importante sítio para prospecção de novos protótipos em decorrência da riqueza de espécies vegetais relacionada a uma possível diversidade química. Programas de triagem têm sido introduzidos no Brasil contrapondo a devastação de florestas relacionadas a atividades rurais, extrativismo madeireiro e mineral. Ensaios em larga escala permitem a análise de um grande número de amostras em um tempo relativamente pequeno, e pode ser considerado como o método mais eficaz para a descoberta de novos fármacos a partir de plantas. Dados atualizados relativos a programas de triagem que objetivam a identificação de novos protótipos antitumorais e antibacterianos são comentados

Extracts from Amazonian plants have inhibitory activity against tyrosinase: an in vitro evaluation

Dermatological disorders related to pigmentation result in tenuous hyper or hypopigmentation Cosmetic and pharmaceutical products containing depigmenting substances are used in the treatment of patients who have high pigmentation disorders, such as melasma or chloasma, post-inflammatory hyperpigmentation, senile lentigo and ephelides. Skin lightening agents are not yet totally effective or safe and therefore intensive research for the discovery of new agents is continuous. Enzyme inhibitors involved in melanogenesis, such as tyrosinase, have been discovered in Asian countries, including those isolated from plant extracts. The Brazilian flora has the highest species diversity in the world, and the chemical, pharmacological and cosmetic potential for the discovery of new skin whitening agents is in proportion with this biodiversity. For these reasons, 25 aqueous and 24 organic extracts obtained from 19 plants native to the Amazon rain forest and to the Atlantic forest, belonging to 11 different families, were evaluated as tyrosinase inhibitors. Nine out of 49 extracts showed inhibitory activity in the screening process. The 50% inhibitory activity (IA50) was calculated, revealing that the most active extracts were the organic extracts from the leaves and stem of Ruprechtia sp. (IA50 33.76 mg.mL-1) and the organic extract from the aerial organs of Rapanea parviflora (IA50 64.19 mg.mL-1).Problemas dermatológicos relacionados com a pigmentação resultam em hiperpigmentações ou hipopigmentação cutâneas. Produtos cosméticos e farmacêuticos com atividade despigmentante são utilizados para o tratamento de pacientes que apresentam distúrbios de hiperpigmentação, tais como melasma ou cloasma, hiperpigmentação pós-inflamatória, lentigem senil e efélides. Os despigmentantes atualmente utilizados não são totalmente eficazes ou seguros, razão pela qual há intensa pesquisa, principalmente em países asiáticos, com a finalidade de se obter novos agentes com esta ação, em especial inibidores de enzimas envolvidas na melanogênese, como a tirosinase. Considerando-se que algumas substâncias obtidas de plantas apresentam essa atividade, a flora brasileira constitui-se uma fonte potencial de obtenção de novos despigmentantes. Por essa razão, 25 extratos aquosos e 24 orgânicos obtidos de 19 plantas da Floresta Amazônica e Mata Atlântica, provenientes de 11 diferentes famílias, foram avaliados quanto à atividade de inibição da tirosinase. Do total de 49 extratos testados, 9 mostraram atividade. Os valores de concentração da atividade inibitória 50% (AI 50%), foram calculados e o mais ativo foi o extrato orgânico das folhas e caule de Ruprechtia sp. (AI50 33,76 mg.mL-1) seguido do extrato orgânico dos órgãos aéreos de Rapanea parviflora (AI50 64,19 mg.mL-1)

Antibacterial activity of Apocynaceae extracts and MIC of Tabernaemontana angulata stem organic extract

Thirty-eight aqueous and organic extracts obtained from 11 Amazonian Apocynaceae species were submitted to an antimicrobial dilution in broth media screening for Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, performed on microtiter plates. The organic extract obtained from the stem of Tabernaemontana angulata presented activity against Gram positive Staphylococcus aureus. The minimal inhibitory concentration of the organic crude extract was 2.50-1.25 mg/mL. Cloramphenicol was used as standard. Alkaloids and triterpenes were found in the active organic extract.Trinta e oito extratos orgânicos e aquosos obtidos de 11 espécies de Apocynaceae foram submetidos a triagem utilizando o método da microdiluição em caldo contra Staphylococcus aureus, Pseudomonas aeruginosa e Candida albicans. O extrato orgânico obtido do caule de Tabernaemontana angulata apresentou atividade contra a bactéria Gram positiva S. aureus. A concentração inibitória mínima verificada para esse extrato variou de 2,50 a 1,25 mg/mL. Cloranfenicol foi utilizado como antimicrobiano padrão. A análise fitoquímica indicou a presença de triterpenos e alcalóides no extrato ativo

Ineffective penicillin treatment and absence of partner treatment may drive the congenital syphilis epidemic in Brazil

BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35–8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77–23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07–4.58), and maternal nontreponemal titers ≥1:64 (1.09–1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59–1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02–1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17–1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55–0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.Revisión por pare

HIV-1 heterosexual transmission and association with sexually transmitted infections in the era of treatment as prevention

Objectives: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. Methods: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3–16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. Results: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p = 0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55–61.2; p = 0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. Conclusions: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting

Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil

Background: An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. Methods: A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. Results: The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2–4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. Conclusions: ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression

Predictors of Enhancing Human Physical Attractiveness: Data from 93 Countries

People across the world and throughout history have gone to great lengths to enhance their physical appearance. Evolutionary psychologists and ethologists have largely attempted to explain this phenomenon via mating preferences and strategies. Here, we test one of the most popular evolutionary hypotheses for beauty-enhancing behaviors, drawn from mating market and parasite stress perspectives, in a large cross-cultural sample. We also test hypotheses drawn from other influential and non-mutually exclusive theoretical frameworks, from biosocial role theory to a cultural media perspective. Survey data from 93,158 human participants across 93 countries provide evidence that behaviors such as applying makeup or using other cosmetics, hair grooming, clothing style, caring for body hygiene, and exercising or following a specific diet for the specific purpose of improving ones physical attractiveness, are universal. Indeed, 99% of participants reported spending \u3e10 min a day performing beauty-enhancing behaviors. The results largely support evolutionary hypotheses: more time was spent enhancing beauty by women (almost 4 h a day, on average) than by men (3.6 h a day), by the youngest participants (and contrary to predictions, also the oldest), by those with a relatively more severe history of infectious diseases, and by participants currently dating compared to those in established relationships. The strongest predictor of attractiveness-enhancing behaviors was social media usage. Other predictors, in order of effect size, included adhering to traditional gender roles, residing in countries with less gender equality, considering oneself as highly attractive or, conversely, highly unattractive, TV watching time, higher socioeconomic status, right-wing political beliefs, a lower level of education, and personal individualistic attitudes. This study provides novel insight into universal beauty-enhancing behaviors by unifying evolutionary theory with several other complementary perspectives