Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UEFS |
Texto Completo: | http://localhost:8080/tede/handle/tede/298 |
Resumo: | INTRODUCTION: Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most important causes of heart failure in America. Alternative therapies have been investigated as potential therapeutic options for patients with this disease. This study evaluated the effects of therapy with human immunoglobulin in an experimental model of chronic chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes of the Colombian strain of T. cruzi, and after eight months of infection were treated with intravenous human immunoglobulin or albumin (control). Before and after 2 months of treatment, infected animals and normal controls underwent cardiac evaluation including electrocardiogram, echocardiography and treadmill test. The immunoglobulin and albumin groups were treated, respectively, with 1 mg/kg/day of human immunoglobulin or albumin, intraperitoneally, for five consecutive days. All animals were sacrificed under anesthesia, after 2 months of treatment, for histopathological analysis of the heart. RESULTS: No improvement was observed in cardiovascular function in animals treated with immunoglobulin compared to animals treated with albumin. There was an increasing in the number of animals with complete atrioventricular block in the immunoglobulin group. However, sections of hearts in immunoglobulin group had a significantly reduced number of inflammatory cells (p <0,01) and area of fibrosis (p <0,001), compared to animals treated with albumin. In animals treated with immunoglobulin, there was evidence of arteritis marked with immune complex deposition in the intima of arterioles. The concentrations of serum cytokines were increased in the group treated with immunoglobulin in comparison to the other groups (uninfected and treated with albumin mice). When considering cytokines production in heart extract, there were no differences observed in production of IFN-γ, TNF-α and IL-10 between the groups treated with immunoglobulin and albumin. CONCLUSION: Thus, we concluded that immunoglobulin therapy has neither not shown anti-inflammatory efficacy nor improvement in cardiovascular function in a murine model of chronic chagasic cardiomyopathy. |
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Santos, Ricardo Ribeiro dos02205263800http://lattes.cnpq.br/9396403739008267Soares, Milena Botelho Pereirahttp://lattes.cnpq.br/352696493160997536509823553http://lattes.cnpq.br/6042864898658969Rabelo, Márcia Maria Noya2016-02-12T23:10:51Z2011-03-31RABELO, Márcia Maria Noya. Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica. 2011. 96 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2011.http://localhost:8080/tede/handle/tede/298INTRODUCTION: Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most important causes of heart failure in America. Alternative therapies have been investigated as potential therapeutic options for patients with this disease. This study evaluated the effects of therapy with human immunoglobulin in an experimental model of chronic chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes of the Colombian strain of T. cruzi, and after eight months of infection were treated with intravenous human immunoglobulin or albumin (control). Before and after 2 months of treatment, infected animals and normal controls underwent cardiac evaluation including electrocardiogram, echocardiography and treadmill test. The immunoglobulin and albumin groups were treated, respectively, with 1 mg/kg/day of human immunoglobulin or albumin, intraperitoneally, for five consecutive days. All animals were sacrificed under anesthesia, after 2 months of treatment, for histopathological analysis of the heart. RESULTS: No improvement was observed in cardiovascular function in animals treated with immunoglobulin compared to animals treated with albumin. There was an increasing in the number of animals with complete atrioventricular block in the immunoglobulin group. However, sections of hearts in immunoglobulin group had a significantly reduced number of inflammatory cells (p <0,01) and area of fibrosis (p <0,001), compared to animals treated with albumin. In animals treated with immunoglobulin, there was evidence of arteritis marked with immune complex deposition in the intima of arterioles. The concentrations of serum cytokines were increased in the group treated with immunoglobulin in comparison to the other groups (uninfected and treated with albumin mice). When considering cytokines production in heart extract, there were no differences observed in production of IFN-γ, TNF-α and IL-10 between the groups treated with immunoglobulin and albumin. CONCLUSION: Thus, we concluded that immunoglobulin therapy has neither not shown anti-inflammatory efficacy nor improvement in cardiovascular function in a murine model of chronic chagasic cardiomyopathy.INTRODUÇÃO: A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, é uma das mais importantes causas de insuficiência cardíaca na América. Terapias alternativas vêm sendo investigadas como possíveis opções terapêuticas para pacientes portadores desta doença. Neste estudo foram avaliados os efeitos da terapia com imunoglobulina humana em um modelo experimental de cardiomiopatia chagásica crônica. MÉTODOS: Camundongos C57BL/6 foram infectados com 1000 tripomastigotas da cepa Colombiana de T. cruzi e, após oito meses de infecção, foram tratados com imunoglobulina ou com albumina humanas (controle). Antes e após 2 meses do tratamento, os animais chagásicos e controles normais foram submetidos à avaliação cardíaca, incluindo eletrocardiograma, ecocardiograma e teste ergométrico. Os grupos tratados com imunoglobulina e albumina receberam, respectivamente, 1 mg/Kg/dia de imunoglobulina humana ou albumina, via intraperitoneal, por cinco dias consecutivos. Todos os animais foram sacrificados sob anestesia após 2 meses de tratamento, para análise histopatológica do coração. RESULTADOS: Não foi observada uma melhora da função cardiovascular no grupo tratado com imunoglobulina quando comparado ao grupo tratado com albumina. Houve um aumento do número de animais com bloqueio atrioventricular total no grupo imunoglobulina. No entanto, secções de corações de camundongos do grupo imunoglobulina apresentaram uma redução significativa do número de células inflamatórias (p< 0,01) e da área de fibrose (p< 0,001) em comparação com animais chagásicos tratados com albumina, sendo que nos animais tratados com imunoglobulina foi evidenciada a presença de arterite acentuada, com depósito de imunocomplexos na camada íntima arteriolar. As concentrações de 12 citocinas séricas foram aumentadas no grupo tratado com imunoglobulina em relação aos demais grupos (não infectados e tratados com albumina). Quando avaliada a produção, em extrato de coração, de IFN-γ, TNF-α e IL-10, não foram observadas diferenças entre os grupos tratados com imunoglobulina e albumina. CONCLUSÃO: Deste modo, concluímos que a terapia com imunoglobulina humana não demonstrou eficácia anti-inflamatória nem induziu a melhora da função cardíaca no modelo murino de cardiomiopatia chagásica crônica.Submitted by Luis Ricardo Andrade da Silva (lrasilva@uefs.br) on 2016-02-12T23:10:51Z No. of bitstreams: 1 Márcia Maria Noya Rabelo - Dissertação.pdf: 26908510 bytes, checksum: 90ce9ed15229c185d93e1b1379da4d1a (MD5)Made available in DSpace on 2016-02-12T23:10:51Z (GMT). No. of bitstreams: 1 Márcia Maria Noya Rabelo - Dissertação.pdf: 26908510 bytes, checksum: 90ce9ed15229c185d93e1b1379da4d1a (MD5) Previous issue date: 2011-03-31application/pdfporUniversidade Estadual de Feira de SantanaMestrado Acadêmico em BiotecnologiaUEFSBrasilDEPARTAMENTO DE CIÊNCIAS BIOLÓGICASCardiomiopatia chagásica crônicaImunoglobulina humanaModelo experimentalChronic chagasic cardiomyopathyHuman immunoglobulinExperimental modelCIENCIAS BIOLOGICASAvaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônicaEvaluation of the therapeutic effects of human immunoglobulin in murine model of chronic chagasic cardiomyopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-54735432730516527826006006005026123383450589282-3439178843068202161info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEFSinstname:Universidade Estadual de Feira de Santana (UEFS)instacron:UEFSORIGINALMárcia Maria Noya Rabelo - Dissertação.pdfMárcia Maria Noya Rabelo - Dissertação.pdfapplication/pdf26908510http://tede2.uefs.br:8080/bitstream/tede/298/2/M%C3%A1rcia+Maria+Noya+Rabelo+-+Disserta%C3%A7%C3%A3o.pdf90ce9ed15229c185d93e1b1379da4d1aMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82089http://tede2.uefs.br:8080/bitstream/tede/298/1/license.txt7b5ba3d2445355f386edab96125d42b7MD51tede/2982016-02-12 20:10:51.832oai:tede2.uefs.br:8080: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.uefs.br:8080/PUBhttp://tede2.uefs.br:8080/oai/requestbcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.bropendoar:2016-02-12T23:10:51Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS)false |
dc.title.por.fl_str_mv |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the therapeutic effects of human immunoglobulin in murine model of chronic chagasic cardiomyopathy |
title |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
spellingShingle |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica Rabelo, Márcia Maria Noya Cardiomiopatia chagásica crônica Imunoglobulina humana Modelo experimental Chronic chagasic cardiomyopathy Human immunoglobulin Experimental model CIENCIAS BIOLOGICAS |
title_short |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
title_full |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
title_fullStr |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
title_full_unstemmed |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
title_sort |
Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica |
author |
Rabelo, Márcia Maria Noya |
author_facet |
Rabelo, Márcia Maria Noya |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Santos, Ricardo Ribeiro dos |
dc.contributor.advisor1ID.fl_str_mv |
02205263800 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9396403739008267 |
dc.contributor.advisor-co1.fl_str_mv |
Soares, Milena Botelho Pereira |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/3526964931609975 |
dc.contributor.authorID.fl_str_mv |
36509823553 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6042864898658969 |
dc.contributor.author.fl_str_mv |
Rabelo, Márcia Maria Noya |
contributor_str_mv |
Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira |
dc.subject.por.fl_str_mv |
Cardiomiopatia chagásica crônica Imunoglobulina humana Modelo experimental |
topic |
Cardiomiopatia chagásica crônica Imunoglobulina humana Modelo experimental Chronic chagasic cardiomyopathy Human immunoglobulin Experimental model CIENCIAS BIOLOGICAS |
dc.subject.eng.fl_str_mv |
Chronic chagasic cardiomyopathy Human immunoglobulin Experimental model |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS |
description |
INTRODUCTION: Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most important causes of heart failure in America. Alternative therapies have been investigated as potential therapeutic options for patients with this disease. This study evaluated the effects of therapy with human immunoglobulin in an experimental model of chronic chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes of the Colombian strain of T. cruzi, and after eight months of infection were treated with intravenous human immunoglobulin or albumin (control). Before and after 2 months of treatment, infected animals and normal controls underwent cardiac evaluation including electrocardiogram, echocardiography and treadmill test. The immunoglobulin and albumin groups were treated, respectively, with 1 mg/kg/day of human immunoglobulin or albumin, intraperitoneally, for five consecutive days. All animals were sacrificed under anesthesia, after 2 months of treatment, for histopathological analysis of the heart. RESULTS: No improvement was observed in cardiovascular function in animals treated with immunoglobulin compared to animals treated with albumin. There was an increasing in the number of animals with complete atrioventricular block in the immunoglobulin group. However, sections of hearts in immunoglobulin group had a significantly reduced number of inflammatory cells (p <0,01) and area of fibrosis (p <0,001), compared to animals treated with albumin. In animals treated with immunoglobulin, there was evidence of arteritis marked with immune complex deposition in the intima of arterioles. The concentrations of serum cytokines were increased in the group treated with immunoglobulin in comparison to the other groups (uninfected and treated with albumin mice). When considering cytokines production in heart extract, there were no differences observed in production of IFN-γ, TNF-α and IL-10 between the groups treated with immunoglobulin and albumin. CONCLUSION: Thus, we concluded that immunoglobulin therapy has neither not shown anti-inflammatory efficacy nor improvement in cardiovascular function in a murine model of chronic chagasic cardiomyopathy. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-03-31 |
dc.date.accessioned.fl_str_mv |
2016-02-12T23:10:51Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
RABELO, Márcia Maria Noya. Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica. 2011. 96 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
dc.identifier.uri.fl_str_mv |
http://localhost:8080/tede/handle/tede/298 |
identifier_str_mv |
RABELO, Márcia Maria Noya. Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica. 2011. 96 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
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UEFS |
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Universidade Estadual de Feira de Santana |
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