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.

Impact on human health of particulate matter emitted from burnings in the Brazilian Amazon region

OBJECTIVE: To analyze the impact on human health of exposure to particulate matter emitted from burnings in the Brazilian Amazon region. METHODS: This was an ecological study using an environmental exposure indicator presented as the percentage of annual hours (AH%) of PM2.5 above 80 μg/m3. The outcome variables were the rates of hospitalization due to respiratory disease among children, the elderly and the intermediate age group, and due to childbirth. Data were obtained from the National Space Research Institute and the Ministry of Health for all of the microregions of the Brazilian Amazon region, for the years 2004 and 2005. Multiple regression models for the outcome variables in relation to the predictive variable AH% of PM2.5 above 80 μg/m3 were analyzed. The Human Development Index (HDI) and mean number of complete blood counts per 100 inhabitants in the Brazilian Amazon region were the control variables in the regression analyses. RESULTS: The association of the exposure indicator (AH%) was higher for the elderly than for other age groups (β = 0.10). For each 1% increase in the exposure indicator there was an increase of 8% in child hospitalization, 10% in hospitalization of the elderly, and 5% for the intermediate age group, even after controlling for HDI and mean number of complete blood counts. No association was found between the AH% and hospitalization due to childbirth. CONCLUSIONS: The indicator of atmospheric pollution showed an association with occurrences of respiratory diseases in the Brazilian Amazon region, especially in the more vulnerable age groups. This indicator may be used to assess the effects of forest burning on human health.

Air pollution and hospital admissions for respiratory diseases in the subequatorial Amazon: a time series approach

The objective of the study is to evaluate the effect of the daily variation in concentrations of fine particulate matter (diameter less than 2.5µm - PM2.5) resulting from the burning of biomass on the daily number of hospitalizations of children and elderly people for respiratory diseases, in Alta Floresta and Tangará da Serra in the Brazilian Amazon in 2005. This is an ecological time series study that uses data on daily number of hospitalizations of children and the elderly for respiratory diseases, and estimated concentration of PM2.5. In Alta Floresta, the percentage increases in the relative risk (%RR) of hospitalization for respiratory diseases in children were significant for the whole year and for the dry season with 3-4 day lags. In the dry season these measurements reach 6% (95%CI: 1.4-10.8). The associations were sig-nificant for moving averages of 3-5 days. The %RR for the elderly was significant for the current day of the drought, with a 6.8% increase (95%CI: 0.5-13.5) for each additional 10µg/m3 of PM2.5. No as-sociations were verified for Tangara da Serra. The PM2.5 from the burning of biomass increased hospitalizations for respiratory diseases in children and the elderly.

Dependence of the crossover exponent with the diffusion rate in the generalized contact process model

We study how the crossover exponent, phi, between the directed percolation (DP) and compact directed percolation (CDP) behaves as a function of the diffusion rate in a model that generalizes the contact process. Our conclusions are based in results pointed by perturbative series expansions and numerical simulations, and are consistent with a value phi = 2 for finite diffusion rates and phi = 1 in the limit of infinite diffusion rate.

Detecção de contaminantes em espécie bioindicadora (Corbicula fluminea) - Rio Ribeira de Iguape - SP

The study assessed heavy metal concentrations in the tissue samples of Corbiculafluminea, by ICP-OES. In the tissues, average levels of 23.99 µg/g of Cu, 144.21 µg/g of Zn, 0.71 µg/g of Cd, 7.10 µg/g of Cr and 2.41 µg/g of Pb were detected ahowing that this last value is high and above the ANVISA reference (2.00 µg/g) for fish and other products. The results suggest that natural processes occuring in the Ribeira de Iguape River are not sufficient for purification so that metals remain in the water and can accumulate in the trophic chain.

Interações entre evolução sedimentar e ocupação humana pré-histórica na costa centro-sul de Santa Catarina, Brasil

Desde o começo da ocupação humana no litoral centro-sul de Santa Catarina, Brasil, a articulação entre processos naturais e antrópicos modelou uma paisagem fortemente domesticada, marcada pela construção massiva de concheiros de dimensões monumentais e pela permanência milenar. Na planície costeira entre Passagem da Barra (município de Laguna) e lago Figueirinha (município de Jaguaruna), 76 sambaquis foram mapeados, dos quais 48 possuem datação. O levantamento sistemático de sítios e datações permitiu identificar padrões de distribuição espacial nos sambaquis da região, quanto a contexto sedimentar da época de construção, estratigrafia e idade. Desse modo, reconheceram-se nos sítios da região: cinco contextos geológico-geomorfológicos de localização; três padrões estratigráficos; e quatro fases de ocupação sambaquieira baseadas na quantidade de sítios e no tipo de padrão construtivo dominante. O modelo integrado de evolução sedimentar e distribuição tempo-espacial de sambaquis indica que estes sítios eram construídos em áreas já emersas e pouco alagáveis, e que sítios interiores, afastados dos corpos lagunares, podem não se ter preservado ou não estarem expostos devido ao processo de assoreamento contínuo que caracterizou a região após a máxima transgressão holocênica. O cruzamento de dados aqui proposto evidencia a importância de abordagens integradas entre arqueologia e geociências no estudo da evolução das paisagens.

Heavy metal concentrations in soils from a remote oceanic island, Fernando de Noronha, Brazil

This paper examines the role of parent rock, pedogenetic processes and airborne pollution in heavy metal accumulation in soils from a remote oceanic island, Fernando de Noronha, Brazil. We studied five soil profiles developed from different volcanic rocks. Mineralogical composition and total concentrations of major and trace elements were determined in 43 samples. The obtained concentrations range for heavy metals were: Co: 26-261 ppm; Cu: 35-97 ppm; Cr: 350-1446 ppm; Ni: 114-691 ppm; Zn: 101-374 ppm; Hg: 2-150 ppb. The composition of soils is strongly affected by the geochemical character of the parent rock. Pedogenesis appears to be responsible for the accumulation of Zn, Co, and, to a lesser extent, of Ni and Cu, in the upper, Mn- and organic carbon-enriched horizons of the soil profiles. Pedogenic influence may also explain the relationship observed between Cr and the Fe. Hg is likely to have been added to the soil profile by long-range atmospheric transport. Its accumulation in the topsoil was further favoured by the formation of stable complexes with organic matter. Clay minerals do not appear to play an important role in the fixation of heavy metals.

Biogeochemical processes and the diversity of Nhecolândia lakes, Brazil

The Pantanal of Nhecolândia, the world's largest and most diversified field of tropical lakes, comprises approximately 10,000 lakes, which cover an area of 24,000 km² and vary greatly in salinity, pH, alkalinity, colour, physiography and biological activity. The hyposaline lakes have variable pHs, low alkalinity, macrophytes and low phytoplankton densities. The saline lakes have pHs above 9 or 10, high alkalinity, a high density of phytoplankton and sand beaches. The cause of the diversity of these lakes has been an open question, which we have addressed in our research. Here we propose a hybrid process, both geochemical and biological, as the main cause, including (1) a climate with an important water deficit and poverty in Ca2+ in both superficial and phreatic waters; and (2) an elevation of pH during cyanobacteria blooms. These two aspects destabilise the general tendency of Earth's surface waters towards a neutral pH. This imbalance results in an increase in the pH and dissolution of previously precipitated amorphous silica and quartzose sand. During extreme droughts, amorphous silica precipitates in the inter-granular spaces of the lake bottom sediment, increasing the isolation of the lake from the phreatic level. This paper discusses this biogeochemical problem in the light of physicochemical, chemical, altimetric and phytoplankton data.

Dose de exposição radiométrica de granitos do estado de Rondônia, Brasil

Este trabalho avaliou a concentração dos radioelementos K, eU e eTh em amostras de granitos do Estado de Rondônia, Brasil. A análise estatística dos dados obtidos indicou que eles seguem distribuições lognormais. Os valores modais encontrados correspondem a cerca de 11% para K, 29 ppm para eU e 85 ppm para eTh. Correlações diretas significativas foram determinadas entre as concentrações dos três radioelementos, isto é, r = 0,71 (entre K e eU), r = 0,72 (entre K e eTh)e r = 0,72 (entre eU e eTh), sugerindo que são congruentes os processos de seu acúmulo nos minerais das rochas analisadas. Os dados de concentração permitiram estimar a taxa de dose absorvida de radiação no ar acima de 1 m do nível do terreno, a qual também segue uma distribuição lognormal, com valor modal de 2,7 mSv/ano, que é ligeiramente superior à média global de 2,4 mSv/ano. Os resultados obtidos também permitiram avaliar, do ponto de vista radiométrico, se os granitos analisados são adequados para emprego como revestimento em construção civil.

Remoção de Pb2+ e Cr3+ em solução por zeólitas naturais associadas a rochas eruptivas da formação serra geral, bacia sedimentar do Paraná

The capacity of natural zeolites and its host rock (dacite) to remove Pb2+ and Cr3+ from aqueous solutions has been investigated. Results showed that both samples prefer to remove Pb2+ instead of Cr3+. Almost 100% of Pb2+ was removed from solutions with concentration until 50 mg L-1 and 100 mg L-1 of this metal, respectively by dacite and zeolite. The equilibrium of metals adsorption process was reached during the first 30 min by both materials. Na+ can be used to recover Pb2+, but not to remove Cr3+ from the treated samples. The Sips model showed a good fit for experimental data of this study.