Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-05-29Bitstream added on 2014-06-13T19:02:35Z : No. of bitstreams: 1 moraes_cfv_dr_botfm.pdf: 589173 bytes, checksum: c968ecfb4e13b9f57ab7e0f45cc65f43 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Hepatite C é uma das principais causas de doença crônica hepática. A combinação entre o interferon peguilado e a ribavirina tem sido considerado o padrão-ouro de tratamento para Hepatite C. A resposta ao tratamento vem sendo associada a fatores ambientais, do vírus e também do paciente, tais como polimorfismos genéticos dos antígenos leucocitários humanos (HLA), da interleucina-10 e do fator de necrose tumoral-a. Plaquetas possuem em suas membranas glicoproteínas que expressam segmentos protéicos polimórficos, os quais são chamados de antígenos plaquetários humanos (HPA). Os sistemas HPA-1, -3, -4 e -5 residem em integrinas, proteínas que possuem interações com interferon. O objetivo desse estudo foi avaliar a associação entre freqüência dos HPA-1, -3, -4 e -5 e a resposta ao tratamento, em 138 pacientes tratados para Hepatite C. A genotipagem dos HPA-1, -3 e -4 foi realizada pela técnica de PCR-SSP e do HPA-5 pela PCR-RFLP. A genotipagem do HCV foi realizada através do Kit comercial INNO-LiPA® v.1.0 (Innogenetics, Ghent, Belgium), segundo as instruções do fabricante. Os pacientes foram divididos em grupos e subgrupos de acordo com o esquema terapêutico, a resposta ao tratamento e o genótipo do HCV. Os pacientes que possuíam o genótipo do HCV não-1 e que foram tratados com IFN-a+RBV, com falha terapêutica, apresentaram uma diferença estatística significante (p<0.05) nas freqüências alélicas e genotípicas do sistema HPA-3, com aumento do alelo 3b. O sistema HPA-3 está localizado em uma integrina que se liga a fibronectina, um receptor de interferon. Nesse contexto, a alteração conformacional glicoprotéica decorrente da presença do alelo HPA-3b, poderia estar associada à falha ao tratamento com IFN-a+RBV em pacientes portadores de genótipo viral não-1. / Hepatic fibrosis leading cirrhosis in 20 to 30% of patients with chronic hepatitis C virus (HCV) infection. Rapid progression to fibrosis has been related to environmental, viral and host factors. However, genetic polymorphisms have recently been associated with this progression, including the expression of integrins. Platelet membrane glycoproteins express several polymorphic antigenic determinants on their surface, which are called human platelet antigens (HPA). HPA-1, -3, -4 and -5 reside in integrins. The association between HPA antigens and stage of fibrosis can determine if HPA is related to progression of fibrosis. Thus, the goal of this study was to determine the association between the HPA-1, -3, -4 and -5 and the liver fibrosis stage in 175 HCV-infected patients. HPA-1, -3 and -4 genotyping was performed by PCR-SSP and, HPA-5 by PCR-RFLP. Fibrosis progression was evaluated using the METAVIR scoring system. There were no significant differences (p>0.05) in allelic and genotypic frequency distribution of HPA-1, -3 and -5, residing in integrins.

Resumo: O presente estudo teve por objetivo descrever características sóciodemográficas, psicossociais, clínicas, índices de qualidade de vida, ocorrência de transtorno mental comum, de sintomas depressivos de pacientes portadores de Hepatite C crônica, em tratamento no Ambulatório de Hepatites Virais da Disciplina de Gastroenterologia Clínica do HC da FMB-UNESP, em três momentos de seu tratamento com Interferon Peguilado e Ribavirina: antes do início, nas 12ª e 24ª semanas de tratamento. Foram também estudadas as associações das variáveis sócio-demográficas e clínicas, de transtorno mental comum (TMC), sintomas depressivos, da forma de tratamento com índices de qualidade de vida (QV) nos três momentos estudados e com os resultados de exames indicativos da resposta virológica ao tratamento (detecção do RNA do vírus da Hepatite C pelo método de PCR). Método: Realizou-se estudo transversal e de seguimento. Uma amostra de conveniência foi estabelecida, tendo-se estudado 82 pacientes no estudo transversal e feito o seguimento de 46 no terceiro e sexto mês após o início do tratamento. Utilizou-se formulário estruturado para investigar aspectos sócio-demográficos e clínicos. Sintomas depressivos foram avaliados pelo Beck Depression Inventory (BDI). Utilizou-se o Self Reporting Questionnaire (SRQ) para avaliar Transtorno Mental Comum e o uso nocivo de álcool foi avaliado por meio do Alcohol Use Disorders Identification Test (AUDIT). A qualidade de vida foi estudada por meio do The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36). O estudo das associações entre variáveis categoriais foi feito pelo teste do Qui-quadrado (ou Fisher, se adequado). Os Testes de Mann-Whitney e de Kruskal Wallis foram utilizados para comparar as distribuições dos vários domínios do SF-36. Para comparação entre os dados nos momentos subseqüentes foram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study aimed at describing socio-demographic, psychosocial and clinical characteristics as well as quality of life indexes, occurrence of common mental disorder and depressive symptoms of patients with chronic hepatitis C undergoing treatment at the Viral Hepatitis Outpatient Unit of the Botucatu Medical School - UNESP, at three different moments of their treatment with Peguilated Interferon and Ribavirin: immediately before treatment, 12 and 24 weeks after its introduction. The association of socio-demographic and clinical variables as well as those for common mental disorder (CMD), depression symptoms and form of treatment with quality-of-life (QL) indexes was evaluated at the three studied moments. The association of such variables with test results indicating virological response to treatment (detection of the hepatitis C virus RNA by the PCR method) was also investigated. Method: A convenience sample was established, and 82 patients were studied in a cross-sectional and follow-up investigation. Forty-six patients were followed 3 and 6 months after the beginning of treatment. A structured questionnaire was used to investigate socio-demographic and clinical aspects. Depression symptoms were evaluated by the Beck Depression Inventory (BDI). The Self Reporting Questionnaire (SRQ) was utilized to evaluate common mental disorder, and harmful use of alcohol was evaluated by the Alcohol Use Disorders Identification Test (AUDIT). Quality of life was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The study of the associations between categorial variables was performed by the chi-square test (or Fisher, if adequate). The Mann-Whitney and Kruskal Wallis tests were used to compare the distribution of various domains of SF-36. McNemar's Exact Test was used for category variables to compare the data at the subsequent moments, and Friedman's Test was... (Complete abstract click electronic access below) / Orientador: Ana Teresa de Abreu Ramos-Cerqueira / Coorientador: Giovanni Faria Silva / Banca: Fani Eta Korn Malerbi / Banca: Carlos Antonio Caramori / Mestre

The work described in this thesis documents the development of new rhodium(I)-catalysed methodologies within two areas of research. The first examines the use of carbonyls as chelating groups in hydroacylation to produce synthetically valuable ketones and enones. The second area explores new carbon-carbon bond activation methodologies. Chapter 1 presents a literature review of the historical development of rhodium-catalysed hydroacylation, with a focus on chelating groups that can currently be used to suppress decarbonylation. A brief review of methodologies that avoid the requirement for a tether is also included. Chapter 2 describes the development of a novel hydroacylation methodology employing carbonyl-based functional groups as tethers on aldehyde substrates. The chapter begins with the optimisation studies for the hydroacylation of &beta;-formyl amides with terminal and internal alkynes, allenes and terminal alkenes, and subsequently explores the substrate scope for each case. The chapter then outlines the investigations undertaken with 1,4-dicarbonyl and 1,5-dicarbonyl systems, N-formyl amides, &beta;-formyl esters and finally &beta;-formyl ketones. A detailed description of the routes undertaken to synthesise each starting material is also presented. Chapter 3 presents a short review surveying the key milestones in the development of carbon-carbon activation methodologies. The chapter begins with a theoretical comparison to carbon-hydrogen activation and a discussion of the unique challenges that are faced. An overview of the major strategies employed to enact these processes is subsequently presented for both strained and unstrained substrates. Chapter 4 outlines the attempts undertaken to develop a novel carbon-carbon bond activation methodology. The work evaluates sulfur-, nitrogen- and alkene-based chelating groups, known to be successful in hydroacylation, in analogous ketone substrates. Chapter 5 discusses the conclusions from this work and the potential for further work. Chapter 6 presents the experimental procedures and data.

No description available.

Monóxido de carbono é a impureza mais comum encontrada em hidrogênio obtido a partir da reforma catalítica ou via hidrocarbonetos. Hidrogênio contaminado com CO diminui drasticamente o desempenho dos ânodos de células a combustível tipo PEM, especialmente quando Pt é utilizada, diminuindo assim os sítios disponíveis para a oxidação de H2. Neste trabalho catalisadores bimetálicos (PtRu e PtMo) e trimetálicos (PtRuMo) suportados em carbono de alta área superficial foram sintetizados através de duas rotas de síntese: impregnação e poliol. Os materiais foram caracterizados através das técnicas de difração de Raios X (DRX), Energia Dispersiva de Raios X (EDX), Microscopia Eletrônica de Transmissão (TEM) e Espectroscopia Fotoeletrônica de Raios X (XPS), e avaliados frente a reação de oxidação de hidr gênio, utilizando H2 puro e H2 contaminado com CO, através de medidas em célula unitária, como ânodos de PEMFC. Os catalisadores ternários apresentaram o melhor desempenho frente a ROH, e os catalisadores tratado a 600 ºC em atmosfera redutora e obtido utilizando o método do poliol com segundo agente redutor apresentaram melhor tolerância a CO. Através dos testes de envelhecimento acelerado (TEA), constatou-se uma menor perda de desempenho para o catalisador PtRuMo/C tratado a 600 ºC em atmosfera redutora. A espectrometria de massa permitiu identificar CO2 e CH4 como produtos da oxidação. / Carbon monoxide is one of the most common impurities in hydrogen fuel obtained from the catalytic reforming of hydrocarbons. CO-contaminated hydrogen drastically decreases the performance of the anodes of PEM fuel cell type, especially when Pt is used, by CO adsorption, reducing the available sites for oxidation H2. In this work bimetallic catalysts (PtRu and PtMo) and trimetallic (PtRuMo) supported on high surface area carbon were synthesized via two synthetic routes: impregnation and polyol. The materials were characterized by X-ray diffraction, energy dispersive X-ray analysis, transmission electron microscopy and X-ray photoelectron spectroscopy, and evaluated towards hydrogen oxidation reaction (HOR), using pure H2 and H2 contaminated with CO, through measurements in the unit cell, as anode of PEMFC. Ternary catalysts showed better performance to HOR, while the catalysts treated at 600 ° C in a reducing atmosphere and the one obtained using the polyol method using a second reducing agent had the best CO tolerance. Accelerated Aging Tests (AGT) evidenced a minor loss of performance for the PtRuMo catalyst treated at 600 °C. Mass spectrometry permitted the identification of CO2 and CH4 as oxidation products.

Monóxido de carbono é a impureza mais comum encontrada em hidrogênio obtido a partir da reforma catalítica ou via hidrocarbonetos. Hidrogênio contaminado com CO diminui drasticamente o desempenho dos ânodos de células a combustível tipo PEM, especialmente quando Pt é utilizada, diminuindo assim os sítios disponíveis para a oxidação de H2. Neste trabalho catalisadores bimetálicos (PtRu e PtMo) e trimetálicos (PtRuMo) suportados em carbono de alta área superficial foram sintetizados através de duas rotas de síntese: impregnação e poliol. Os materiais foram caracterizados através das técnicas de difração de Raios X (DRX), Energia Dispersiva de Raios X (EDX), Microscopia Eletrônica de Transmissão (TEM) e Espectroscopia Fotoeletrônica de Raios X (XPS), e avaliados frente a reação de oxidação de hidr gênio, utilizando H2 puro e H2 contaminado com CO, através de medidas em célula unitária, como ânodos de PEMFC. Os catalisadores ternários apresentaram o melhor desempenho frente a ROH, e os catalisadores tratado a 600 ºC em atmosfera redutora e obtido utilizando o método do poliol com segundo agente redutor apresentaram melhor tolerância a CO. Através dos testes de envelhecimento acelerado (TEA), constatou-se uma menor perda de desempenho para o catalisador PtRuMo/C tratado a 600 ºC em atmosfera redutora. A espectrometria de massa permitiu identificar CO2 e CH4 como produtos da oxidação. / Carbon monoxide is one of the most common impurities in hydrogen fuel obtained from the catalytic reforming of hydrocarbons. CO-contaminated hydrogen drastically decreases the performance of the anodes of PEM fuel cell type, especially when Pt is used, by CO adsorption, reducing the available sites for oxidation H2. In this work bimetallic catalysts (PtRu and PtMo) and trimetallic (PtRuMo) supported on high surface area carbon were synthesized via two synthetic routes: impregnation and polyol. The materials were characterized by X-ray diffraction, energy dispersive X-ray analysis, transmission electron microscopy and X-ray photoelectron spectroscopy, and evaluated towards hydrogen oxidation reaction (HOR), using pure H2 and H2 contaminated with CO, through measurements in the unit cell, as anode of PEMFC. Ternary catalysts showed better performance to HOR, while the catalysts treated at 600 ° C in a reducing atmosphere and the one obtained using the polyol method using a second reducing agent had the best CO tolerance. Accelerated Aging Tests (AGT) evidenced a minor loss of performance for the PtRuMo catalyst treated at 600 °C. Mass spectrometry permitted the identification of CO2 and CH4 as oxidation products.

ITC/USA 2007 Conference Proceedings / The Forty-Third Annual International Telemetering Conference and Technical Exhibition / October 22-25, 2007 / Riviera Hotel & Convention Center, Las Vegas, Nevada / Increasingly, many software developers are facing the challenge of adapting software applications developed on one platform to work on multiple platforms. While software standards have helped this effort, they do not go far enough, and many platforms only partially support these standards leaving many needed functions in platform specific libraries. This is particularly evident in the areas of graphics and user interfaces, threading and synchronization, and in network and file access. Fortunately, Java offers a common interface where native libraries diverge. This paper outlines a phased strategy for migrating platform specific applications to be platform independent while reusing the robust, existing algorithms.

No description available.

A series of studies in mice were performed to determine the interaction of two sulfur nucleophiles, oral n-acetylcysteine (NAC) and intravenous sodium thiosulfate (Na₂S₂O₃) with the anticancer drug mitomycin C (MMC). Neither nucleophile reduced MMC lethality or hematopoietic toxicity. Both increased the antitumor activity of MMC in mice bearing P-388 and L-1210 leukemias. There was no nucleophile reduction of MMC effects on normal bone marrow stem cells (CFUs) using a murine spleen colony forming assay. In contrast, the nucleophiles significantly enhanced MMC bone marrow toxicity. Three clonogenic human tumor cell lines (HEC-1A endometrial, 8226 myeloma, WiDr colon) were relatively resistant to MMC and the nucleophiles did not increase activity. A human breast cancer cell line (MCF-7) was sensitive to MMC and this activity was blocked by glutathione. Oxygen free radical scavengers did not reduce MMC activity. A novel isocratic high performance liquid chromatography (HPLC) assay (48:52, methanol:0.01M phosphate buffer) using ultraviolet detection at 365 nm was used to characterize MMC-protein binding and murine pharmacokinetics. The k' for MMC was 7.91 and 9.86 for porfiromycin. Peaks were confirmed by mass spectroscopy. MMC was bound 30% to albumin and S-9 microsomal proteins and 60-70% to calf thymus DNA. MMC uptake into mouse bone marrow was enhanced by the nucleophiles and was rapidly cleared from the plasma (half-life 0.5 hours). In vitro MMC metabolism with rat liver S-9 microsomes demonstrated production of a polar eluting, putative MMC metabolite (K' = 4.486, lambda maximum 300 nm). This metabolite was inactive in the in vitro clonogenic tumor cell assay. Finally, molecular pharmacology studies using alkaline DNA elution showed that MMC causes both DNA-DNA and DNA-protein crosslinks. There was no evidence for free radical-induced DNA strand scission by MMC. There was also some evidence of moderate DNA protection with the sulfur nucleophiles.

No description available.