Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8), fructose (n=8), and fructose+ simvastatin (n=8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32%/min) relative to that in the control group (4.4+ 0.29%/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66%/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 + 7 bpm) compared with that in the control (48 + 7 bpm) and fructose+simvastatin groups (31+8 bpm). The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm) compared with that in control (49 + 9 bpm) and fructose animals (46+5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.

Epidemiologia da leishmaniose tegumentar americana no Estado do Acre, Amazônia brasileira

Efetuou-se estudo estatístico descritivo em 8.516 casos de leishmaniose tegumentar americana no Estado do Acre, Brasil, no período de 2001 a 2006 (segundo período), comparando-se com os resultados de publicação anterior com dados no mesmo estado entre 1992 e 1997 (primeiro período). A prevalência no estado mais que dobrou entre os dois momentos (55,7/10 mil habitantes de 1992 a 1997 e 128,5/10 mil habitantes entre 2001 e 2006. O sexo masculino foi o mais acometido (68,8%, n = 5.860) no segundo período. A média das idades foi de 26,3 anos, valor discretamente menor do que o do primeiro período. Pacientes com baixa escolaridade foram os mais acometidos pela doença. As demais variáveis avaliadas foram zona de residência, ocupação, critério de diagnóstico, forma clínica, tratamento, recidiva, tempo para procurar tratamento e evolução da doença. Conclui-se que houve piora nos indicadores epidemiológicos da leishmaniose tegumentar americana avaliados no estado entre os períodos estudados.

Antiplatelet activity of Croton celditifolius

Croton celtidifolius Baill is a tree found in the Atlantic Forest South of Brazil, mainly in Santa Catarina. The bark and leaf infusions of this medicinal plant have been popularly used for the treatment of inflammatory diseases. The anti-aggregant activity of C. celtidifolius crude extract (CE) and the column chromatography (CC) isolated compounds flavonoids, catechin and gallocatechin were evaluated in human blood platelets. The platelet-rich plasma (PRP) was incubated with different concentrations of flavonóides (50 - 200 µg/mL) to be tested before platelet aggregation was induced by the agonists adenosine 5'diphosphate (ADP) and collagen. At 200 µg/mL the CE, catechin and gallocatechin markedly inhibited platelet aggregation with the aggregant agents. Using ATP production as an index of platelet secretory capacity, we observed a decreased production of ATP in platelets treated with flavonoids when stimulated by collagen. On the other hand, the flavonoids did not promote inhibitory effect on prothrombin time (PT), thromboplastin time (APTT) and thrombin time (TT). In conclusion, these observations suggest that C. celtidifolius is likely to exert an inhibitory action on platelets in vitro by suppressing secretion and platelet aggregation.

Acessibilidade dos sítios web dos governos estaduais brasileiros: uma análise quantitativa entre 1996 e 2007

A utilização da web para a disponibilização de informações e serviços de órgãos governamentais para os cidadãos tem se tornado cada vez mais expressiva. Assim, a garantia de que esses conteúdos e serviços possam ser acessíveis a qualquer cidadão é imprescindível, independentemente de necessidades especiais ou de quaisquer outras barreiras. No Brasil, o Decreto-Lei nº5.296/2004 determinou que todos os órgãos governamentais deveriam adaptar seus sítios na web de acordo com critérios de acessibilidade até dezembro de 2005. Com o objetivo de verificar a evolução da acessibilidade ao longo dos anos e como foi o impacto dessa legislação, este artigo analisa a acessibilidade dos sítios dos governos estaduais brasileiros por meio de amostras coletadas entre 1996 e 2007. Foram efetuadas análises por meio de métricas, obtidas por avaliações com ferramentas automáticas. Os resultados indicam que a legislação teve pouco impacto para a melhoria real da acessibilidade dos sítios no período indicado, com uma melhora somente em 2007. Verifica-se que se faz necessário adotar políticas públicas mais efetivas para que as pessoas com necessidades especiais tenham os seus direitos para acesso a informações e aos serviços públicos na web assegurados mais amplamente.

Da estratégia individual à ação coletiva: grupos de suporte e gênero no contexto da gestão da diversidade

Este artigo trata da formação de grupo de suporte no marco das políticas de diversidade empresarial. São escassas as pesquisas que abordem essa prática de gestão da diversidade. Visando a contribuir para o preenchimento dessa lacuna, o trabalho analisa um Comitê de Mulheres, a fim de compreender de que forma ele é influenciado pela política de diversidade formatada pela direção da organização e a influencia. Foi realizado um estudo de caso etnográfico em uma corporação transnacional cuja sede no Brasil está localizada em São Paulo. Os resultados apontam para um paradoxo. Por um lado, o Comitê analisado representa um processo de emancipação, sinalizando para práticas gerenciais mais inclusivas e participativas. Por outro, notou-se a presença de mecanismos de controle, uma vez que há um esforço da direção da empresa em disciplinar o seu funcionamento.

A phylogenetic analysis of Brycon and Henochilus (Characiformes, Characidae, Bryconinae) based on the mitochondrial gene 16S rRNA

The genus Brycon, the largest subunit of the Bryconinae, has 42 valid species distributed from southern Mexico to the La Plata River in Argentina. Henochilus is a monotypic genus, comprising a single species (H. wheatlandii) found in the upper Rio Doce basin. In the present study, partial sequences of the mitochondrial gene 16S were obtained for fifteen species of Brycon and for Henochilus wheatlandii. The results showed that the genus Brycon is paraphyletic, since Henochilus is the sister-group of B. ferox and B. insignis. The most basal species analyzed were the trans-Andean species B. henni, B. petrosus, and B. chagrensis.

Richards growth model and viability indicators for populations subject to interventions

In this work we study the problem of modeling identification of a population employing a discrete dynamic model based on the Richards growth model. The population is subjected to interventions due to consumption, such as hunting or farming animals. The model identification allows us to estimate the probability or the average time for a population number to reach a certain level. The parameter inference for these models are obtained with the use of the likelihood profile technique as developed in this paper. The identification method here developed can be applied to evaluate the productivity of animal husbandry or to evaluate the risk of extinction of autochthon populations. It is applied to data of the Brazilian beef cattle herd population, and the the population number to reach a certain goal level is investigated.

Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results

Enzyme kinetics, structural analysis and molecular modeling studies on a series of Schistosoma mansoni PNP inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the development of novel drugs against schistosomiasis, a neglected tropical disease that affects about 200 million people worldwide. In the present work, enzyme kinetic studies were carried out in order to determine the potency and mechanism of inhibition of a series of SmPNP inhibitors. In addition to the biochemical investigations, crystallographic and molecular modeling studies revealed important molecular features for binding affinity towards the target enzyme, leading to the development of structure-activity relationships (SAR).

Structural and chemical basis for anticancer activity of a series of 'beta'-tubulin ligands: molecular modeling and 3D QSAR studies

An important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity.

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 μg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % > 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.

Ensino de astronomia em um espaço não formal: observação do Sol e de manchas solares

O presente artigo analisa os resultados obtidos num minicurso sobre o Sol e sua dinâmica realizado no Observatório Astronômico do Centro de Divulgação Científica e Cultural (CDCC) pertencente à Universidade de São Paulo (USP) na cidade de São Carlos para alunos do ensino fundamental. As atividades foram desenvolvidas na recente inaugurada, Sala Solar. Ela é dedicada ao estudo do Sol, enfatizando a observação de manchas solares e do espectro do Sol. A metodologia adotada no minicurso consistiu em pequenos experimentos, observações e diálogos expositivos. Isto incentivou os estudantes a tomarem decisões, fazerem questionamentos e refletirem gerando pensamentos mais críticos e produzindo um maior número de conexões entre o real e o abstrato que contribuiu para níveis de maior complexidade conceitual verificados durante entrevistas semiestruturadas e nas respostas ao questionário final.

Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos

Neglected diseases are a major global cause of illness, long-term disability and death. Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. The existing drug therapy suffers from a combination of drawbacks including poor efficacy, resistance and serious side effects. In 2009, we celebrate the 100th anniversary of the discovery of Chagas' disease, facing the challenges of developing new, safe and effective drugs for the treatment of this disease. This brief review attempts to highlight the state of the art, limitations and perspectives of Chagas' disease drug development.

The effects of nitric oxide on the immune response during giardiasis

Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.