Avaliação dos efeitos da terapia com imunoglobulina humana em modelo murino de cardiomiopatia chagásica crônica

Detalhes bibliográficos
Autor(a) principal: Rabelo, Márcia Maria Noya
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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spelling 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:tede/298Tk9UQTogQ09MT1FVRSBBUVVJIEEgU1VBIFBSP1BSSUEgTElDRU4/QQpFc3RhIGxpY2VuP2EgZGUgZXhlbXBsbyA/IGZvcm5lY2lkYSBhcGVuYXMgcGFyYSBmaW5zIGluZm9ybWF0aXZvcy4KCkxJQ0VOP0EgREUgRElTVFJJQlVJPz9PIE4/Ty1FWENMVVNJVkEKCkNvbSBhIGFwcmVzZW50YT8/byBkZXN0YSBsaWNlbj9hLCB2b2M/IChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSA/IFVuaXZlcnNpZGFkZSAKWFhYIChTaWdsYSBkYSBVbml2ZXJzaWRhZGUpIG8gZGlyZWl0byBuP28tZXhjbHVzaXZvIGRlIHJlcHJvZHV6aXIsICB0cmFkdXppciAoY29uZm9ybWUgZGVmaW5pZG8gYWJhaXhvKSwgZS9vdSAKZGlzdHJpYnVpciBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhPz9vIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyP25pY28gZSAKZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zID91ZGlvIG91IHY/ZGVvLgoKVm9jPyBjb25jb3JkYSBxdWUgYSBTaWdsYSBkZSBVbml2ZXJzaWRhZGUgcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250ZT9kbywgdHJhbnNwb3IgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YT8/byAKcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhPz9vLgoKVm9jPyB0YW1iP20gY29uY29yZGEgcXVlIGEgU2lnbGEgZGUgVW5pdmVyc2lkYWRlIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGM/cGlhIGEgc3VhIHRlc2Ugb3UgCmRpc3NlcnRhPz9vIHBhcmEgZmlucyBkZSBzZWd1cmFuP2EsIGJhY2stdXAgZSBwcmVzZXJ2YT8/by4KClZvYz8gZGVjbGFyYSBxdWUgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YT8/byA/IG9yaWdpbmFsIGUgcXVlIHZvYz8gdGVtIG8gcG9kZXIgZGUgY29uY2VkZXIgb3MgZGlyZWl0b3MgY29udGlkb3MgCm5lc3RhIGxpY2VuP2EuIFZvYz8gdGFtYj9tIGRlY2xhcmEgcXVlIG8gZGVwP3NpdG8gZGEgc3VhIHRlc2Ugb3UgZGlzc2VydGE/P28gbj9vLCBxdWUgc2VqYSBkZSBzZXUgCmNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3U/bS4KCkNhc28gYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YT8/byBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jPyBuP28gcG9zc3VpIGEgdGl0dWxhcmlkYWRlIGRvcyBkaXJlaXRvcyBhdXRvcmFpcywgdm9jPyAKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzcz9vIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgPyBTaWdsYSBkZSBVbml2ZXJzaWRhZGUgCm9zIGRpcmVpdG9zIGFwcmVzZW50YWRvcyBuZXN0YSBsaWNlbj9hLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3Q/IGNsYXJhbWVudGUgCmlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIG5vIHRleHRvIG91IG5vIGNvbnRlP2RvIGRhIHRlc2Ugb3UgZGlzc2VydGE/P28gb3JhIGRlcG9zaXRhZGEuCgpDQVNPIEEgVEVTRSBPVSBESVNTRVJUQT8/TyBPUkEgREVQT1NJVEFEQSBURU5IQSBTSURPIFJFU1VMVEFETyBERSBVTSBQQVRST0M/TklPIE9VIApBUE9JTyBERSBVTUEgQUc/TkNJQSBERSBGT01FTlRPIE9VIE9VVFJPIE9SR0FOSVNNTyBRVUUgTj9PIFNFSkEgQSBTSUdMQSBERSAKVU5JVkVSU0lEQURFLCBWT0M/IERFQ0xBUkEgUVVFIFJFU1BFSVRPVSBUT0RPUyBFIFFVQUlTUVVFUiBESVJFSVRPUyBERSBSRVZJUz9PIENPTU8gClRBTUI/TSBBUyBERU1BSVMgT0JSSUdBPz9FUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKQSBTaWdsYSBkZSBVbml2ZXJzaWRhZGUgc2UgY29tcHJvbWV0ZSBhIGlkZW50aWZpY2FyIGNsYXJhbWVudGUgbyBzZXUgbm9tZSAocykgb3UgbyhzKSBub21lKHMpIGRvKHMpIApkZXRlbnRvcihlcykgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIGRhIHRlc2Ugb3UgZGlzc2VydGE/P28sIGUgbj9vIGZhcj8gcXVhbHF1ZXIgYWx0ZXJhPz9vLCBhbD9tIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2VuP2EuCg==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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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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