Made available in DSpace on 2014-06-11T19:24:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-11-23Bitstream added on 2014-06-13T20:12:20Z : No. of bitstreams: 1 peresi_e_me_botfm_prot.pdf: 2017467 bytes, checksum: 9eace176fa7814cebf281490fa4801d1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A tuberculose é uma doença ainda em expansão, que foi declarada pela Organização Mundial da Saúde, em 1995, emergência sanitária mundial. Dificultam seu controle a longa duração do tratamento e ausência de marcadores para medir o sucesso ou a falha deste tratamento. Na patogenia da tuberculose, citocinas como IFN-γ e TNF-α tem papel fundamental, pois são responsáveis pela interação do linfócito T com o macrófago infectado, fator central da imunidade protetora contra o M. tuberculosis, sendo também produzidas durante essa interação. Como as citocinas pró-inflamatórias... / Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the WHO in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-y and TNF-a., a central factor in immune response against M. tuberculosis, are responsible for the interaction between T Iymphocytes and the infected macrophage, and are also produced during this interaction. As proinflammatory cytokines have a close relationship with micobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute phase response (APR) as a result of homeostatic and physiological responses also induced by them. Acute phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-y, TNF-a, IL-10, and TGF-13 production in supernatant of peripheral blood mononuclear cells (PBMC) and monocytes (MO) cultures, and the serum acute phase response through total protein, albumin, globulins, C-reactive protein (CRP), a-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (HC-FMB) were evaluated once and 28 (G2) pulmonary tuberculosis patients: 13 from HC-FMB and 15 from the Bauru State Health Secretary. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20mL of peripheral blood (ELlSA), with or without activation: LPS for MO culture and PHA for PBMC culture... (Complete abstract click electronic access below)

Orientador: Jussara Marcondes Machado / Banca: Sueli Aparecida Calvi / Banca: Maria Foschiani Dias Baptista / Resumo: A tuberculose é uma doença ainda em expansão, que foi declarada pela Organização Mundial da Saúde, em 1995, emergência sanitária mundial. Dificultam seu controle a longa duração do tratamento e ausência de marcadores para medir o sucesso ou a falha deste tratamento. Na patogenia da tuberculose, citocinas como IFN-γ e TNF-α tem papel fundamental, pois são responsáveis pela interação do linfócito T com o macrófago infectado, fator central da imunidade protetora contra o M. tuberculosis, sendo também produzidas durante essa interação. Como as citocinas pró-inflamatórias... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the WHO in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-y and TNF-a., a central factor in immune response against M. tuberculosis, are responsible for the interaction between T Iymphocytes and the infected macrophage, and are also produced during this interaction. As proinflammatory cytokines have a close relationship with micobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute phase response (APR) as a result of homeostatic and physiological responses also induced by them. Acute phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-y, TNF-a, IL-10, and TGF-13 production in supernatant of peripheral blood mononuclear cells (PBMC) and monocytes (MO) cultures, and the serum acute phase response through total protein, albumin, globulins, C-reactive protein (CRP), a-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (HC-FMB) were evaluated once and 28 (G2) pulmonary tuberculosis patients: 13 from HC-FMB and 15 from the Bauru State Health Secretary. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20mL of peripheral blood (ELlSA), with or without activation: LPS for MO culture and PHA for PBMC culture... (Complete abstract click electronic access below) / Mestre

Submitted by Maykon Nascimento (maykon.albani@hotmail.com) on 2015-08-19T18:55:05Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Estudo sobre acetilacaoo da isoniazida em pacientes com Tuberculose pulmonar e da sua implicacao na reducao ou eliminacao da carga bacilar no escarro.pdf: 4242930 bytes, checksum: a16179fb880340385234f8f9fad6bdee (MD5) / Approved for entry into archive by Patricia Barros (patricia.barros@ufes.br) on 2015-08-20T16:11:14Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Estudo sobre acetilacaoo da isoniazida em pacientes com Tuberculose pulmonar e da sua implicacao na reducao ou eliminacao da carga bacilar no escarro.pdf: 4242930 bytes, checksum: a16179fb880340385234f8f9fad6bdee (MD5) / Made available in DSpace on 2015-08-20T16:11:14Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Estudo sobre acetilacaoo da isoniazida em pacientes com Tuberculose pulmonar e da sua implicacao na reducao ou eliminacao da carga bacilar no escarro.pdf: 4242930 bytes, checksum: a16179fb880340385234f8f9fad6bdee (MD5) Previous issue date: 2013 / A N-acetiltransferase 2 é a principal enzima responsável pelo metabolismo e inativação da isoniazida no organismo humano. Mutações no gene NAT2 levam a 3 perfis genotípicos de acetilação que alteram os níveis séricos do fármaco: acetiladores lentos, intermediários e rápidos, o que pode alterar o desfecho terapêutico. O objetivo do estudo foi investigar se os diferentes perfis podem influenciar no tempo de negativação da cultura de escarro, e se existe correlação entre carga bacilar e gravidade da doença com tempo de conversão da cultura. A população de estudo foi composta por 62 pacientes, que tiveram seus DNAs sequenciados para identificação de mutações no gene NAT2 e seus perfis de acetilação determinados. A análise genotípica detectou 10 SNPs, sendo as mutações 341 T>C (39,65%) e 481 C>T (38,71%) as mais frequentes. A determinação das variantes alélicas identificou NAT2*5B (29,03%), NAT2*6A (23,39%) e NAT2*4 (24,19%) como os alelos mais frequentes e NAT2*5B/*5B como o genótipo mais frequente (20,4%). Dentre os 62 pacientes, foi possível correlacionar tempo de negativação da cultura e perfil de acetilação entre 43 deles, os quais 58,3% e 55,6% tiveram o genótipo lento com maior frequência no mês 1 e mês 3, respectivamente. Por meio de dados microbiológicos, a carga bacilar e a gravidade da doença também foram comparadas com o tempo de negativação, indicando que os pacientes com doença moderada ou avançada (76,7%) e aqueles com carga bacilar alta (60,4%), não tiveram associação estatística com o tempo de conversão da cultura. Por último, curvas de crescimento de isolados de M. tuberculosis de pacientes foram construídas para verificar possíveis diferenças na duração da fase lag entre os isolados, porém não foi observada diferença estatística entre elas. Com base nos resultados encontrados, verifica-se que não existe associação entre o perfil de acetilação do paciente, a carga bacilar, a gravidade da doença e o tempo de negativação da cultura de escarro / N-acetyltransferase 2 is the main enzyme responsible for the metabolism and inactivation of isoniazid in humans. Mutations in the gene NAT2 lead to 3 profiles of acetylation genotype that modify serum levels of the drug: slow acetylators, intermediate and fast, which can change the therapeutic outcome. The aim of the study was to investigate whether different profiles can influence the time of negativation sputum culture, and if there is a correlation between bacterial load and disease severity with time to culture conversion. The study population comprised 62 patients who had their DNAs sequenced for identification of mutations in the gene NAT2 and to determine the acetylation. Genotypic analysis detected 10 SNPs, and SNPs 341 T>C (39.65%) and 481 C>T (38.71%) were the most frequent. The determination of allelic variants identified NAT2*5B (29.03%), NAT2*6A (23.39%) and NAT2*4 (24.19%) as alleles more frequent and NAT2*5B/5B as the most frequent genotype (20.4%). Among 62 patients, it was possible to correlate time of negative culture and acetylation profile of 43 them, which 58.3% and 55.6% had genotype slow with greater frequency in month 1 and months 3, respectively. Through microbiological data, the bacterial load and severity of disease were also compared with the time of negativation, indicating that patients with moderate or advanced disease (76.7%) and those with high bacterial load (60.4%) had no statistical association with the conversion time of culture. Finally, growth curves of strains of M. tuberculosis of patients were constructed to evaluate possible differences in the duration of the lag phase between the isolates, but there was no statistical difference between them. Based on these results, it is found that there is no association between the profile acetylation of the patient, bacterial load and the severity of the illness and the time of negative sputum cultures