975 resultados para anti-infective agents


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

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Angiogenesis inhibitors have gained much public attention recently as anti-cancer agents and several are currently in clinical trials, including angiostatin (Phase I, Thomas Jefferson University Hospital, Philadelphia, PA). We report here the bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle structure to be determined. All three kringle lysine-binding sites contain a bound bicine molecule of crystallization while the former of kringle 2 and kringle 3 are cofacial. Moreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is sufficient to accommodate the a-helix of the 30 residue pepticle VEK-30 found in the kringle 2/VEK-30 complex. Together the three kringles produce a central cavity suggestive of a unique domain where they may function in concert. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

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OBJETIVO: No contexto de acesso universal à terapia antiretroviral, os resultados do Programa de Aids dependem da qualidade do cuidado prestado. O objetivo do estudo foi avaliar a qualidade do cuidado dos serviços ambulatoriais que assistem pacientes de Aids. MÉTODOS: Estudo realizado em sete Estados brasileiros, em 2001 e 2002. Foi avaliada a qualidade do atendimento a pacientes com Aids quanto à disponibilidade de recursos e a organização do trabalho de assistência. Um questionário com 112 questões estruturadas abordando esses aspectos, foi enviado a 336 serviços. RESULTADOS: A taxa de resposta foi de 95,8% (322). Os indicadores de disponibilidade de recursos mostram uma adequação maior do que os indicadores de organização do trabalho. Não faltam antiretrovirais em 95,5% dos serviços, os exames de CD4 e Carga Viral estão disponíveis em quantidade adequada em 59 e 41% dos serviços, respectivamente. em 90,4% dos serviços há pelo menos um profissional não médico (psicólogo, enfermeiro ou assistente social). Quanto à organização, 80% não agendavam consulta médica com hora marcada; 40,4% agendavam mais que 10 consultas médicas por período; 17% não possuíam gerentes exclusivos na assistência e 68,6% não realizavam reuniões sistemáticas de trabalho com a equipe. CONCLUSÕES: Os resultados apontam que além de garantir a distribuição mais homogênea de recursos, o programa precisa investir no treinamento e disseminação do manejo do cuidado, conforme evidenciado nos resultados da organização de trabalho.

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An understanding of isoniazid (INH) drug resistance mechanism in Mycobacterium tuberculosis should provide significant insight for the development of newer anti-tubercular agents able to control INH-resistant tuberculosis (TB). The inhA-encoded 2-trans enoyl-acyl carrier protein reductase enzyme (InhA) has been shown through biochemical and genetic studies to be the primary target for INH. In agreement with these results, mutations in the inhA structural gene have been found in INH-resistant clinical isolates of M. tuberculosis, the causative agent of TB. In addition, the InhA mutants were shown to have higher dissociation constant values for NADH and lower values for the apparent first-order rate constant for INH inactivation as compared to wild-type InhA. Here, in trying to identify structural changes between wild-type and INH-resistant InhA enzymes, we have solved the crystal structures of wild-type and of S94A, I47T and I21V InhA proteins in complex with NADH to resolutions of, respectively, 2.3 angstrom, 2.2 angstrom, 2.0 angstrom, and 1.9 angstrom. The more prominent structural differences are located in, and appear to indirectly affect, the dinucleotide binding loop structure. Moreover, studies on pre-steady-state kinetics of NADH binding have been carried out. The results showed that the limiting rate constant values for NADH dissociation from the InhA-NADH binary complexes (k(off)) were eleven, five, and tenfold higher for, respectively, I21V, I47T and S94A INH-resistant mutants of InhA as compared to INH-sensitive wildtype InhA. Accordingly, these results are proposed to be able to account for the reduction in affinity for NADH for the INH-resistant InhA enzymes. (c) 2006 Elsevier Ltd. All rights reserved.

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Glucocorticoid hormones modulate the actions of peptide growth factors and constitute important therapeutic tools as anti-inflammatory and anti-tumor agents. The C6 rat glioma cell line responds to glucocorticoids with changes in morphology and growth block. The hyper-responsive ST1 cell variant displays a dramatic phenotypic reversion under the influence of these hormones. Thus, the transformed and tumorigenic cells reversibly change to a normal and non-tumorigenic phenotype. In addition, the cells also produce a C-type retrovirus. We used poly A(+) mRNA from ST1 cells that had been treated with hydrocortisone to generate a cDNA library that was then screened, by differential hybridization,for glucocorticoid-responsive cellular sequences. The retroviral genomic RNA was used to generate a viral-specific probe. Cross hybridization led to the isolation of at least 4 cDNA clones of which 3 are cellular sequences and one corresponds to a retroviral gene. These clones were characterized by DNA sequencing and Northern blot hybridization analysis.

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Thrombosis was induced in the jugular vein of guinea pigs by damage of the epithelium with a sclerosing solution. The effect of heparin, Dextran 70, acetylsalicylic acid, dipyridamole and phenylbutazone in preventing the development of the thrombus was investigated. Only heparin in high doses showed this effect.

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A study was conducted to analyze the effects of propolis mouth rinse on the repair of surgical wounds after sulcoplasty by the modified Kazanjian technique. Twenty-seven patients who underwent sulcoplasty were divided into three groups: C1--patients who did not use the mouth rinse C2--patients who used a mouth rinse containing 5% aqueous alcohol T--patients who used a mouth rinse containing 5% propolis in aqueous alcohol solution. The patients returned 7, 14, 30, and 45 days after surgery for cytological and clinical evaluation. It was concluded that: 1) the mouth rinse containing propolis in aqueous alcohol solution aids repair of intra-buccal surgical wounds and exerts a small pain-killing and anti-inflammatory effect; 2) the vehicle employed has a minor irritant effect on intra-buccal surgical wounds; 3) exfoliative cytology allows epithelization of intrabuccal surgical wounds.

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The objective of the present study was to investigate changes in colon wall in rats with fecal peritonitis (Per) associated with sodium diclofenac (SD) by studying breaking strength and tissue collagen concentration. The rats were divided into the following experimental groups: GROUP 1-SD: 60 animals injected intramuscularly with sodium diclofenac at the dose of 2 mg/kg body weight; GROUP 2-Per: 60 animals injected intraperitoneally with a suspension of human feces. Peritonitis was interrupted after six hours of evolution; GROUP 3-Per+SD: 60 animals injected intraperitoneally with a suspension of human feces and receiving SD according to the schedule used for Groups 1 and 2; CONTROL GROUP: 12 animals injected intramuscularly with physiological saline. The animals of Group 1, 2 and 3 were successively sacrificed 2, 4, 7, 14 and 21 days after interruption of peritonitis an/or the beginning of treatment. Under conditions of the experimental model and of the methods used, we conclude that sodium diclofenac, peritonitis and the peritonitis-sodium diclofenac association decrease the breaking strength and the concentration of tissue collagen in the colon segment.

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Tunicamycin, which inhibits N-glycosylation of proteins, was used as a tool to determine the type of linkage which occurs in glycoprotein antigens of Aspergillus fumigatus. When A. fumigatus extracts were electrophoretically separated and blotted then probed with anti-Aspergillus patients' sera, differences in antigenic profiles were noted when tunicamycin-treated samples were compared with controls. Tunicamycin had no detectable effect on the cellular proteinases of A. fumigatus, most of which are glycosylated. Some enzymatic components were lacking when extracellular proteinases were compared with those of control samples. The major catalase component of A. fumigatus is a concanavalin A (Con A)-binding glycoprotein. In cultures grown in the presence of tunicamycin, partiallydeglycosylated catalase components were obtained which could be distinguished from the native catalase by their altered mobilities in polyacrylamide gels. The effect of deglycosylation on catalase antigens was monitored using an antiserum raised to a ConA-binding fraction of A fumigatus mycelium. These antibodies bound both to the native glycoprotein and the partially deglycosylated material. These latter two were largely unaffected when incubated with an antiserum raised to a non-ConA-binding fraction of A. fumigatus which is essentially carbohydrate free. The ability to produce partially-glycosylated antigens of A. fumigatus offers a model to study the effect of basic structural modifications on both the enzymatic and antigenic activities of these molecules.

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The subject of this paper was to study the behavior of the periapical tissues of dogs' teeth after biopulpectomy and dressing with calcium hydroxide or a corticosteroid-antibiotic association, before root canal filling with zinc oxide eugenol (ZOE) or Sealapex sealers. The teeth were overinstrumented and dressed for 7 days before the root canal filling. The animals were sacrificed 180 days after treatment and the specimens were prepared for morphological analysis. Specimens treated with Sealapex presented a higher number of cases with biological closure than ZOE. When the root canals were filled with ZOE, better results were observed with the use of the Ca(OH)2 dressing.