Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 94-104). Also available in print.

Orientador: Domingos Alves Meira / Banca: Rogério de Jesus Pedro / Banca: David Salomão Lewi / Banca: Alexandrina Sartori / Banca: Maria Inês de Moura Campos Pardini / Resumo: Iniciativas como a "WHO/UNAIDS '3 by 5' permitiram que se atingisse, no ano de 2007, a marca de 3 milhões de pessoas com acesso à terapia antiretroviral (TARV) em países de baixa e média renda. O aumento da cobertura nestes países demanda custos importantes com anti-retrovirais, porém também levanta outro problema, que é o monitoramento da terapia em localidades de poucos recursos. Há consenso no fato de que devem ser pesquisados marcadores de eficácia da TARV mais acessíveis. Considerando o comportamento da β-2 microglobulina sérica e das citocinas séricas TNF-α, IFN-γ, IL-2, IL-4 e IL-10 com relação à atividade inflamatória induzida pela replicação do HIV-1, o objetivo deste estudo foi o de verificar o comportamento destas substâncias como indicadores da presença, ou não, de falha terapêutica à HAART. Entre agosto de 2004 e novembro de 2005, 89 indivíduos infectados pelo HIV-1, atendidos pela Área de Doenças Tropicais da Faculdade de Medicina de Botucatu-UNESP, e 20 indivíduos normais, doadores de sangue do Hemocentro de Botucatu [43 mulheres e 66 homens; idade média = 39,7 anos (22 - 66 anos)] foram divididos em 4 grupos: G1- 15 indivíduos infectados pelo HIV-1, virgens de tratamento ou sem HAART há pelo menos seis meses e com contagens de linfócitos T CD4 + menores que 350 células/mm3; G2- 31 indivíduos infectados pelo HIV-1, em uso de HAART e sem falha terapêutica virológica (FT); G3- formado por 43 indivíduos infectados pelo HIV-1, em uso de HAART e com FT, e GC- formado por 20 indivíduos normais, não infectados pelo HIV-1, que serviram de controles para as citocinas séricas. Foram revisados os dados demográficos, clínicos e de HAART e realizados os exames β-2 microglobulina sérica, citocinas séricas (TNF-α, IFN-γ, IL-2, IL-4 e IL-10), genotipagem do HIV-1, carga viral plasmática (CV) e linfócitos T CD4 + e T CD8 +. Para... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Initiatives such as WHO/UNAIDS '3 by 5' made it possible to achieve the figure of 3 million people with access to antiretroviral therapy (ART) in middle- and low-income countries in 2007. The increase in these countries' coverage leads to important expenditure on antiretroviral drugs; however, it also raises another problem, which is therapy monitoring in low-income locations. There is agreement on the fact that more accessible ART efficacy markers must be studied. By considering the behavior of serum β-2 microglobulin and serum cytokines TNF-α, IFN-γ, IL-2, IL-4 and IL-10 in relation to inflammatory activity induced by HIV-1 replication, the objective of this study was to assess the behavior of such substances as indicators of the presence, or not, of antiretroviral therapeutic failure (TF). From August 2004 to November 2005, 89 HIV-1-infected individuals assisted by the Tropical Diseases Sector of the Botucatu School of Medicine - UNESP and 20 normal blood donors at the Blood Transfusion Center of Botucatu [43 female and 66 male; mean age = 39.7 years (22 - 66 years)] were divided into 4 groups: G1- 15 HIV-1-infected individuals, previously untreated or without HAART for at least six months and CD4 + < 350 cells/mm3; G2- 31 HIV-1-infected individuals undergoing HAART without virological therapeutic failure (TF), G3- 43 HIV-1-infected individuals undergoing HAART with TF, and CG- 20 normal individuals who served as controls for serum cytokines. Demographic, clinical and HAART data were reviewed, and serum β-2 microglobulin, serum cytokines (TNFα, IFN-γ, IL-2, IL-4 and IL-10), HIV-1 genotyping, plasma viral load (VL) and T CD4 + and T CD8 + lymphocytes tests were performed. The Mann-Whitney test for independent samples was used for between-group comparison in the case of numeric variables, and Fisher's exact test was applied for category variables. Statistical difference... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:31:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-26Bitstream added on 2014-06-13T20:41:51Z : No. of bitstreams: 1 almeida_ramb_dr_botfm.pdf: 853261 bytes, checksum: 866edf2277c1ac0e74ea9c48e8cb31a9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Iniciativas como a “WHO/UNAIDS ‘3 by 5’ permitiram que se atingisse, no ano de 2007, a marca de 3 milhões de pessoas com acesso à terapia antiretroviral (TARV) em países de baixa e média renda. O aumento da cobertura nestes países demanda custos importantes com anti-retrovirais, porém também levanta outro problema, que é o monitoramento da terapia em localidades de poucos recursos. Há consenso no fato de que devem ser pesquisados marcadores de eficácia da TARV mais acessíveis. Considerando o comportamento da β-2 microglobulina sérica e das citocinas séricas TNF-α, IFN-γ, IL-2, IL-4 e IL-10 com relação à atividade inflamatória induzida pela replicação do HIV-1, o objetivo deste estudo foi o de verificar o comportamento destas substâncias como indicadores da presença, ou não, de falha terapêutica à HAART. Entre agosto de 2004 e novembro de 2005, 89 indivíduos infectados pelo HIV-1, atendidos pela Área de Doenças Tropicais da Faculdade de Medicina de Botucatu-UNESP, e 20 indivíduos normais, doadores de sangue do Hemocentro de Botucatu [43 mulheres e 66 homens; idade média = 39,7 anos (22 - 66 anos)] foram divididos em 4 grupos: G1- 15 indivíduos infectados pelo HIV-1, virgens de tratamento ou sem HAART há pelo menos seis meses e com contagens de linfócitos T CD4 + menores que 350 células/mm3; G2- 31 indivíduos infectados pelo HIV-1, em uso de HAART e sem falha terapêutica virológica (FT); G3- formado por 43 indivíduos infectados pelo HIV-1, em uso de HAART e com FT, e GC- formado por 20 indivíduos normais, não infectados pelo HIV-1, que serviram de controles para as citocinas séricas. Foram revisados os dados demográficos, clínicos e de HAART e realizados os exames β-2 microglobulina sérica, citocinas séricas (TNF-α, IFN-γ, IL-2, IL-4 e IL-10), genotipagem do HIV-1, carga viral plasmática (CV) e linfócitos T CD4 + e T CD8 +. Para... / Initiatives such as WHO/UNAIDS ‘3 by 5’ made it possible to achieve the figure of 3 million people with access to antiretroviral therapy (ART) in middle- and low-income countries in 2007. The increase in these countries’ coverage leads to important expenditure on antiretroviral drugs; however, it also raises another problem, which is therapy monitoring in low-income locations. There is agreement on the fact that more accessible ART efficacy markers must be studied. By considering the behavior of serum β-2 microglobulin and serum cytokines TNF-α, IFN-γ, IL-2, IL-4 and IL-10 in relation to inflammatory activity induced by HIV-1 replication, the objective of this study was to assess the behavior of such substances as indicators of the presence, or not, of antiretroviral therapeutic failure (TF). From August 2004 to November 2005, 89 HIV-1-infected individuals assisted by the Tropical Diseases Sector of the Botucatu School of Medicine – UNESP and 20 normal blood donors at the Blood Transfusion Center of Botucatu [43 female and 66 male; mean age = 39.7 years (22 - 66 years)] were divided into 4 groups: G1- 15 HIV-1-infected individuals, previously untreated or without HAART for at least six months and CD4 + < 350 cells/mm3; G2- 31 HIV-1-infected individuals undergoing HAART without virological therapeutic failure (TF), G3- 43 HIV-1-infected individuals undergoing HAART with TF, and CG- 20 normal individuals who served as controls for serum cytokines. Demographic, clinical and HAART data were reviewed, and serum β-2 microglobulin, serum cytokines (TNFα, IFN-γ, IL-2, IL-4 and IL-10), HIV-1 genotyping, plasma viral load (VL) and T CD4 + and T CD8 + lymphocytes tests were performed. The Mann-Whitney test for independent samples was used for between-group comparison in the case of numeric variables, and Fisher’s exact test was applied for category variables. Statistical difference... (Complete abstract click electronic access below)

Objetivo: avaliar a associação dos níveis séricos de citocinas em gestantes assintomáticas no segundo trimestre e nascimentos pré-termo (NPT). Pacientes e métodos: Estudo caso-controle aninhado a uma coorte de conveniência prospectiva. Foram incluídas gestantes de feto único entre 20 e 25 semanas e 6 dias de idade gestacional de 2 cidades brasileiras, as quais foram submetidas a entrevista e coleta de amostras de sangue venoso e avaliadas por entrevista no momento do nascimento. Dos NPT, 197 foram consideradas como grupo de casos e o grupo controle foi selecionado por sorteio, totalizando 426 pacientes no grupo controle. Foram avaliadas 41 citocinas séricas e comparadas entre os grupos. Resultados: Na primeira análise, as citocinas GRO, PDGF-BB e sCD40L mostraram níveis séricos diminuídos no grupo dos partos pré-termo (PPT) (p<0,05). Analisando apenas os PPT espontâneos, as citocinas GRO, sCD40L e MCP-1 apresentaram níveis diminuídos no grupo de casos (p<0,05). As citocinas que apresentaram níveis séricos com valores discrepantes foram submetidas a uma transformação logarítmica para posterior comparação entre os grupos de casos e controles. No grupo de casos incluindo apenas PPT espontâneos, verificou-se níveis aumentados de IL-2 (p<0,05). Foi significativo entre os grupos caso e controle a incidência de tabagismo materno e histórico de parto pré-termo anterior, sendo então essas características consideradas como fatores de risco nas análises multivariadas das citocinas dosadas. Apenas GRO demonstrou diferença em suas concentrações séricas entre grupos caso e controle na análise multivariada. Conclusão: Níveis séricos menores de GRO no segundo trimestre estão associados a maior risco de prematuridade, podendo refletir uma deficiência na resposta inflamatória materna. / Objective: To evaluate the association between second trimester serum cytokine levels in asymptomatic pregnant women and preterm births (PTB). Patientes and methods: Cohort-nested case-control study including singleton pregnant women between 20 and 25 weeks and 6 days of gestation in two Brazilian cities. The patients were interviewed and collection of venous blood samples was performed. They were again interviewed at time of birth. Among PTB, 197 were considered as case group. The control group was selected among term births (426 patients). Fourty-one cytokines were compared between groups. Results: Cytokines GRO, PDGF-BB and sCD40L showed decreased serum levels in PTB group (p<0.05). When analyzing only spontaneous PTB, GRO, sCD40L and MCP-1 levels showed decreased levels in the case group (p <0.05). A logarithmic transformation was performed among cytokines with discrepant serum levels in an attempt of verifying the outliers influency, and it has shown increased levels of IL-2 in the group of spontaneous preterm delivery (p <0.05). In both analyzes, the incidence of maternal smoking and history of previous preterm delivery was significantly different between case and control groups. In multivariate analysis, only GRO demonstrated different serum levels between case and control groups. Conclusion: Lower second trimester serum levels of GRO in assymptomatic women are associated with increased number of preterm births. This finding may reflect a deficiency in maternal inflammatory response.

Objetivo: avaliar a associação dos níveis séricos de citocinas em gestantes assintomáticas no segundo trimestre e nascimentos pré-termo (NPT). Pacientes e métodos: Estudo caso-controle aninhado a uma coorte de conveniência prospectiva. Foram incluídas gestantes de feto único entre 20 e 25 semanas e 6 dias de idade gestacional de 2 cidades brasileiras, as quais foram submetidas a entrevista e coleta de amostras de sangue venoso e avaliadas por entrevista no momento do nascimento. Dos NPT, 197 foram consideradas como grupo de casos e o grupo controle foi selecionado por sorteio, totalizando 426 pacientes no grupo controle. Foram avaliadas 41 citocinas séricas e comparadas entre os grupos. Resultados: Na primeira análise, as citocinas GRO, PDGF-BB e sCD40L mostraram níveis séricos diminuídos no grupo dos partos pré-termo (PPT) (p<0,05). Analisando apenas os PPT espontâneos, as citocinas GRO, sCD40L e MCP-1 apresentaram níveis diminuídos no grupo de casos (p<0,05). As citocinas que apresentaram níveis séricos com valores discrepantes foram submetidas a uma transformação logarítmica para posterior comparação entre os grupos de casos e controles. No grupo de casos incluindo apenas PPT espontâneos, verificou-se níveis aumentados de IL-2 (p<0,05). Foi significativo entre os grupos caso e controle a incidência de tabagismo materno e histórico de parto pré-termo anterior, sendo então essas características consideradas como fatores de risco nas análises multivariadas das citocinas dosadas. Apenas GRO demonstrou diferença em suas concentrações séricas entre grupos caso e controle na análise multivariada. Conclusão: Níveis séricos menores de GRO no segundo trimestre estão associados a maior risco de prematuridade, podendo refletir uma deficiência na resposta inflamatória materna. / Objective: To evaluate the association between second trimester serum cytokine levels in asymptomatic pregnant women and preterm births (PTB). Patientes and methods: Cohort-nested case-control study including singleton pregnant women between 20 and 25 weeks and 6 days of gestation in two Brazilian cities. The patients were interviewed and collection of venous blood samples was performed. They were again interviewed at time of birth. Among PTB, 197 were considered as case group. The control group was selected among term births (426 patients). Fourty-one cytokines were compared between groups. Results: Cytokines GRO, PDGF-BB and sCD40L showed decreased serum levels in PTB group (p<0.05). When analyzing only spontaneous PTB, GRO, sCD40L and MCP-1 levels showed decreased levels in the case group (p <0.05). A logarithmic transformation was performed among cytokines with discrepant serum levels in an attempt of verifying the outliers influency, and it has shown increased levels of IL-2 in the group of spontaneous preterm delivery (p <0.05). In both analyzes, the incidence of maternal smoking and history of previous preterm delivery was significantly different between case and control groups. In multivariate analysis, only GRO demonstrated different serum levels between case and control groups. Conclusion: Lower second trimester serum levels of GRO in assymptomatic women are associated with increased number of preterm births. This finding may reflect a deficiency in maternal inflammatory response.

Infection is a leading cause of death in hemodialysis patients, partly due to dysfunctional immunity. Frequent dialysis therapy improves patient outcomes and quality of life. We hypothesize that extended home hemodialysis (EHHD) also improves immune function compared to conventional in-hospital hemodialysis (CHD); therefore, we designed a prospective matching-cohort clinical study to assess serum inflammatory markers and the functional capacity of monocyte-derived dendritic cells (MDDCs) and T-lymphocytes. Serum CRP was decreased in EHHD patients suggesting that extended dialysis may decrease inflammatory solute/cytokine levels. Compared to controls, MDDCs from hemodialysis patients had similar endocytic capacity, expression of co-stimulatory molecules, and T-cell activation capacity. However, CHD was associated with the highest expression of CD83 and CD40. Activated T-cells in CHD patients also produced significantly more immunosuppressive IL-10 compared to EHHD patients and controls. Therefore, EHHD may improve immune function by decreasing inflammation, MDDC pre-activation, and synthesis of immunosuppressive cytokines.

Infection is a leading cause of death in hemodialysis patients, partly due to dysfunctional immunity. Frequent dialysis therapy improves patient outcomes and quality of life. We hypothesize that extended home hemodialysis (EHHD) also improves immune function compared to conventional in-hospital hemodialysis (CHD); therefore, we designed a prospective matching-cohort clinical study to assess serum inflammatory markers and the functional capacity of monocyte-derived dendritic cells (MDDCs) and T-lymphocytes. Serum CRP was decreased in EHHD patients suggesting that extended dialysis may decrease inflammatory solute/cytokine levels. Compared to controls, MDDCs from hemodialysis patients had similar endocytic capacity, expression of co-stimulatory molecules, and T-cell activation capacity. However, CHD was associated with the highest expression of CD83 and CD40. Activated T-cells in CHD patients also produced significantly more immunosuppressive IL-10 compared to EHHD patients and controls. Therefore, EHHD may improve immune function by decreasing inflammation, MDDC pre-activation, and synthesis of immunosuppressive cytokines.