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.

Modified silicas covalently bounded to 5,10,15,20-tetrakis(2-hydroxy-5-nitrophenyl)porphyrinato iron(III): synthesis, spectroscopic and EPR characterization. Catalytic studies

In this work we have studied cyclooctene epoxidation with PhIO, using a new iron porphyrin, 5,10,15,20-tetrakis(2-hydroxy-5-nitrophenyl)porphyrinato iron(III), supported on silica matrices via eletrostatic interaction and / or covalent bonds as catalyst. These catalysts were obtained and immobilized on the solid supports propyltrimethylammonium silica (SiN+); propyltrimethylammonium and propylimidazole silica [SiN+(IPG)] and chloropropylsilica (CPS) via elestrostatic interactions and covalent binding. Characterization of the supported catalysts by UV-Vis spectroscopy and EPR (Electron paramagnetic resonance) indicated the presence of a mixture of FeII and FeIII species in all of the three obtained catalysts. In the case of (Z)-cyclooctene epoxidation by PhIO the yields observed for cis-epoxycyclooctane were satisfactory for the reactions catalyzed by the three materials (ranging from 68% to 85%). Such results indicate that immobilization of metalloporphyrins onto solid supports via groups localized on the ortho positions of their mesophenyl rings can lead to efficient catalysts for epoxidation reactions. The catalyst 1-CPS is less active than 1-SiN and 1-SiN(IPG), this argues in favour of the immobilization of this metalloporphyrin onto solids via electrostatic interactions, which is easier to achieve and results in more active oxidation catalysts. Interestingly, the activity of the supported catalysts remained the same even after three successive recyclings; therefore, they are stable under the oxidizing conditions.

Dating minerals by ID-TIMS geochronology at times of in situ analysis: selected case studies from the CPGeo-IGc-USP laboratory

Since 1964, the Center for Geochronological Research - CPGeo, one of the interdepartmental centers of the Instituto de Geociências (IG) of São Paulo University, has developed studies related to several geological processes associated with different rock types. Thermal Ionization Mass Spectrometry Isotopic Dilution (ID-TIMS) has been the technique widely used in the CPGeo U-Pb Laboratory. It provides reliable and accurate results in age determination of superposed events. However, the open-system behavior such as Pb-loss, the inheritance problem and metamictization processes allow and impel us to a much richer understanding of the power and limitations of U-Pb geochronology and thermochronology. In this article, we present the current methodology used at the CPGeo-IGc-USP U-Pb laboratory, the improvements on ID-TIMS method, and report high-precision U-Pb data from zircon, monazite, epidote, titanite, baddeleyite and rutile from different rock types of several domains of the Brazilian south-southeast area, Argentina and Uruguay.

Relações entre preconceito, ideologia e atitudes frente à educação inclusiva

Este artigo analisa atitudes de alunos de um curso de pedagogia frente à educação inclusiva. Parte da hipótese de que o preconceito e a ideologia podem ser obstáculos à inclusão de crianças com deficiência na escola. Foram aplicadas quatro escalas: Manifestação de Preconceito, Atitudes Frente à Educação Inclusiva e Ideologia da Racionalidade Tecnológica, elaboradas por Crochík em 2000, 2003 e 2006, e a escala F, construída por Adorno, Frenkel-Brunswik, Levinson e Sanford em 1950. O estudo foi realizado com 188 estudantes de pedagogia. Os alunos desta amostra tenderam a ser mais favoráveis do que desfavoráveis à educação inclusiva, e foi possível verificar que o preconceito, a adesão à ideologia da racionalidade tecnológica e, implicitamente, ao fascismo, são variáveis que se relacionam às atitudes acerca desse tipo de educação.

Characterization studies of 1-(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane formed from the reaction of hydroxide Ion with 1,3-Bis-(4-cyano pyridinium)propane

The aqueous alkaline reaction of 1,3-bis(4-cyanopyridinium)propane dibromide, a reactant constituted of two pyridinium rings linked by a three-methylene bridge, generates a novel compound,1 -(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane. The reaction pathway is attributed to the proximity of the OH- ion inserted between two pyridinium moieties, which occurs only in bis(pyridinium) derivatives connected by short methylene spacers, where charge-conformational effects are important.

Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

Para viver e pensar além das margens: perspectivas, agenciamentos e desencaixes no campo da saúde pública

Neste ensaio os autores buscam expor ideias, críticas e reflexão ética ao destacarem questões complexas e que requerem a análise densa de estudiosos do campo interdisciplinar da saúde pública. A defesa do ponto de vista dos autores é pensar que a complexidade inerente ao campo requer aproximação mais conseqüente junto às necessidades sociais, criatividade dos agentes públicos, investigação e estudos inovadores que possibilitem uma saúde pública contemporânea e voltada para a realidade brasileira.

Childhood and adolescent obesity and adult mortality: a systematic review of cohort studies

This systematic review addressed cohort studies on obesity in childhood and adolescence and adult mortality, published from January 1990 to March 2007. We searched the PubMed database with the following uniterms: obesity, mortality, child, adolescent; obesity and mortality; overweight and mortality. References were also analyzed. The age limit was 2 to 18 years. Quality of the articles was assessed, and eight were identified and reviewed. All used weight and stature for determination of obesity, and seven used body mass index (BMI). The quality score varied from 9 to 17. Evidence of association between obesity in childhood and adolescence and adult mortality should be viewed with caution. Use of BMI and potential confounders were discussed. Further research is needed to analyze the relationship between childhood and adolescent obesity and adult mortality.

Potential vectors and hosts of rickettsia spp: epidemiological studies in the Vale do Paraíba, state of Rio de Janeiro/Brazil

FAPESP, CNPq, CAPES

Microbiological indicators for the assessment of performance in the hazard analysis and critical control points (HACCP) system in meat lasagna production

The HACCP system is being increasingly used to ensure food safety. This study investigated the validation of the control measures technique in order to establish performance indicators of this HACCP system in the manufacturing process of Lasagna Bolognese (meat lasagna). Samples were collected along the manufacturing process as a whole, before and after the CCPs. The following microorganism s indicator (MIs) was assessed: total mesophile and faecal coliform counts. The same MIs were analyzed in the final product, as well as, the microbiological standards required by the current legislation. A significant reduction in the total mesophile count was observed after cooking (p < 0.001). After storage, there was a numerical, however non-significant change in the MI count. Faecal coliform counts were also significantly reduced (p < 0.001) after cooking. We were able to demonstrate that the HACCP system allowed us to meet the standards set by both, the company and the Brazilian regulations, proved by the reduction in the established indicators

Gender identification of five genera of stingless bees (Apidae, Meliponini) based on wing morphology

Currently, the identification of pollinators is a critical necessity of conservation programs. After it was found that features extracted from patterns of wing venation are sufficient to discriminate among insect species, various studies have focused on this structure. We examined wing venation patterns of males and workers of five stingless bee species in order to determine if there are differences between sexes and if these differences are greater within than between species. Geometric morphometric analyses were made of the forewings of males and workers of Nannotrigona testaceicornis, Melipona quadrifasciata, Frieseomelitta varia, and Scaptotrigona aff. depilis and Plebeia remota. The patterns of males and workers from the same species were more similar than the patterns of individuals of the same sex from different species, and the patterns of both males and workers, when analyzed alone, were sufficiently different to distinguish among these five species. This demonstrates that we can use this kind of analysis for the identification of stingless bee species and that the sex of the individual does not impede identification. Computer-assisted morphometric analysis of bee wing images can be a useful tool for biodiversity studies and conservation programs.

Chemometric Studies on Natural Products as Potential Inhibitors of the NADH Oxidase from Trypanosoma cruzi Using the VolSurf Approach

Natural products have widespread biological activities, including inhibition of mitochondrial enzyme systems. Some of these activities, for example cytotoxicity, may be the result of alteration of cellular bioenergetics. Based on previous computer-aided drug design (CADD) studies and considering reported data on structure-activity relationships (SAR), an assumption regarding the mechanism of action of natural products against parasitic infections involves the NADH-oxidase inhibition. In this study, chemometric tools, such as: Principal Component Analysis (PCA), Consensus PCA (CPCA), and partial least squares regression (PLS), were applied to a set of forty natural compounds, acting as NADH-oxidase inhibitors. The calculations were performed using the VolSurf+ program. The formalisms employed generated good exploratory and predictive results. The independent variables or descriptors having a hydrophobic profile were strongly correlated to the biological data.