818 resultados para rational screening


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Oxacillin is the main drug of choice for the treatment of S. aureus infections. However, S. aureus resistance to oxacillin has become a major problem in the recent decades. The study aimed assess the rates of oxacillin resistance in S. aureus samples obtained at the Botucatu Medical School Hospital, UNESP, and to compare phenotypic techniques for the detection of MRSA against the gold standard method (mecA gene detection) in these samples. A total of 102 samples, previously isolated between 2002 and 2006, and kept at the Culture Collection of the Department of Microbiology and Immunology, in the Botucatu Biosciences Institute, UNESP, were included. Oxacillin resistance was assessed by oxacillin and cefoxitin disk diffusion and agar dilution tests, screening tests using Mueller-Hinton agar with 6 mu g/mL of oxacillin and 4% NaCl, E-test, and mecA gene detection. of the samples analyzed, 46 (45.1%) were mecA-positive. Oxacillin disk sensitivity and specificity were 86.9% and 91.1%, respectively. Cefoxitin disk sensitivity and specificity were respectively 91.3% and 91.1%. The screening test with the cefoxitin disk showed almost the same level of sensitivity (91.3%) and specificity (91.1%). With E-test strips, sensitivity was higher (97.8%) and specificity was comparable to that found with the other methods (91.1%). Ninety-three percent of the samples produced beta-lactamase and five of them were mecA-negative. There was a gradual increase in the number of oxacillin-resistant S. aureus samples between 2002 and 2004. However, from 2004 to 2006, the number of resistant samples dropped from 55% of MRSA in 2004, to 45% in 2005 and 34.6% in 2006. The data obtained reveal that, among phenotypic methods, the E-test yielded the best results, with higher sensitivity levels when compared to the other methods. The decreased resistance rate observed over the most recent years may be explained by the rational use of antimicrobial agents associated with good practices in the control of hospital infection, or may be related to the diminished use of oxacillin as a treatment option.

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Crystallographic screening has been used to identify new inhibitors for potential target for drug development. Here, we describe the application of the crystallographic screening to assess the structural basis of specificity of ligands against a protein target. The method is efficient and results in detailed crystallographic information. The utility of the method is demonstrated in the study of the structural basis for specificity of ligands for human purine nucleoside phosphorylase (PNP). Purine nucleoside phosphorylase catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. This enzyme is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. This methodology may help in the future development of a new generation of PNP inhibitors.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The objective of this research was to investigate xylanase production by filamentous fungi (Trichoderma viride) to determine the best cultivation conditions in the process, aiming toward optimization of enzyme production. The best temperature, as well as the best carbon source, for biomass production was determined through an automated turbidimetric method (Bioscreen-C). The enzyme activity of this fungus was separately evaluated in two solid substrates (wheat and soybean bran) and in Vogel medium, pure and by adding other carbon sources. Temperature effects, cultivation time, and spore concentrations were also tested. The best temperature and carbon source for enzyme and biomass production was 25 C and sorbitol, respectively. Maximum xylanase activity was achieved when the fungus was cultivated in wheat bran along with sorbitol (1%, w/v), using a spore concentration of 2 x 10(6) spores. mL(-1), pH 5.0, for 144 h cultivation. The study demonstrated not only the importance of the nature of the substrate in obtaining a system resistant to catabolic repression, but also the importance of the culture conditions for biosynthesis of this enzyme. T. viride showed a high potential for xylanase production under the conditions presented in these assays.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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We prove that the zeros of the polynomials P.. (a) of degree m, defined by Boros and Moll via[GRAPHICS]approach the lemmiscate {zeta epsilon C: \zeta(2) - 1\ = Hzeta < 0}, as m --> infinity. (C) 2004 Elsevier B.V. All rights reserved.

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The use of medicines during pregnancy deserves special attention from dentists due to the potential risks to fetal development. The prescription of antimicrobial drugs during this period must be based not only on the etiology of the disease but also on the drug's effect on the embryo, which may be toxic, possibly leading to irreversible lesions. Interest in studies of the teratogenic effects of drugs increased in response to reports of the high incidence of phocomelia in patients treated with thalidomide. Although teratogenicity has long been known, pregnant women today are still exposed to this risk. The effects of drugs depend on the level of susceptibility of the fetus and on the period of exposure during pregnancy. In this context, and considering the paucity of studies on this subject in dentistry, the aim of this review was to offer an up-to-date compilation of data on the antimicrobial drugs most frequently used during pregnancy and the effects of their use.

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We present a class of three-dimensional integrable structures associated with the Darboux-Egoroff metric and classical Euler equations of free rotations of a rigid body. They are obtained as canonical structures of rational Landau-Ginzburg potentials and provide solutions to the Painleve VI equation.

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Nonperturbative Wilson coefficients of the operator product expansion (OPE) for the spin-0 glueball correlators are derived and analyzed. A systematic treatment of the direct instanton contributions is given, based on a realistic instanton size distribution and renormalization at the operator scale. In the pseudoscalar channel, topological charge screening is identified as an additional source of (semi-) hard nonperturbative physics. The screening contributions are shown to be vital for consistency with the anomalous axial Ward identity, and previously encountered pathologies (positivity violations and the disappearance of the 0(-+) glueball signal) are traced to their neglect. on the basis of the extended OPE, a comprehensive quantitative analysis of eight Borel-moment sum rules in both spin-0 glueball channels is then performed. The nonperturbative OPE coefficients turn out to be indispensable for consistent sum rules and for their reconciliation with the underlying low-energy theorems. The topological short-distance physics strongly affects the sum rule results and reveals a rather diverse pattern of glueball properties. New predictions for the spin-0 glueball masses and decay constants and an estimate of the scalar glueball width are given, and several implications for glueball structure and experimental glueball searches are discussed.