Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Fragelli, Bruna Dias de Lima
Orientador(a): Anibal, Fernanda de Freitas lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Câmpus São Carlos
Programa de Pós-Graduação: Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/ufscar/10614
Resumo: Schistosomiasis is a disease that affects a large number of people in 78 countries. The number of cases has increased in recent years and there is no vaccine and new drugs, a worrying aspect, since there is loss of sensitivity to the drug used, Praziquantel. The present study aimed to evaluate the effects of the recombinant enzymes of S. mansoni Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) and Purine Nucleoside Phosphorylase (PNP) and the MIX of the two enzymes in the treatment of schistosomiasis in the murine model. Female mice of the Balb / c strain were infected with cercariae and treated intraperitoneally with 3 doses of 100 μg of the proteins at 10 day intervals from the 28th day of infection. Egg numbers were counted in the feces on the 48th and 54th days after infection by the Kato-Katz method. On the 55th day after infection, adult worms were retaken from the hepatic and mesenteric intestinal system, global and differential counts of LCP and blood cells. Cytokines IFN-γ, IL-4 and IL-10 in plasma were also quantified, as well as the production of antibodies of the IgG2a and IgE classes. For the analysis of the granulomas and deposition of collagen histological laminae of the liver were made. Our results demonstrate that treatment with the HGPRT enzyme appears to stimulate the production of IL-4 and IL-10 cytokines and promoted significant reduction of liver granulomas in infected and treated animals. Treatment with the PNP enzyme was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine. The PNP and MIX enzyme treatment were able to reduce the number of eggs in the faeces and negatively modulate the number of eosinophils in the PCL and in the blood. Therefore, treatment with the recombinant enzymes of S. mansoni HGPRT and PNP seems to contribute to the control and reduction of pathophysiological aspects of schistosomiasis, contributing to the reduction of morbidity associated with schistosomiasis in the murine model.
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spelling Fragelli, Bruna Dias de LimaAnibal, Fernanda de Freitashttp://lattes.cnpq.br/4918261968772806Pereira, Humberto D'Munizhttp://lattes.cnpq.br/8681619250791832http://lattes.cnpq.br/014953414206600905291ea2-5ffb-48c9-aec4-e79b88348c0e2018-10-25T17:28:24Z2018-10-25T17:28:24Z2018-02-26FRAGELLI, Bruna Dias de Lima. Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10614.https://repositorio.ufscar.br/handle/ufscar/10614Schistosomiasis is a disease that affects a large number of people in 78 countries. The number of cases has increased in recent years and there is no vaccine and new drugs, a worrying aspect, since there is loss of sensitivity to the drug used, Praziquantel. The present study aimed to evaluate the effects of the recombinant enzymes of S. mansoni Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) and Purine Nucleoside Phosphorylase (PNP) and the MIX of the two enzymes in the treatment of schistosomiasis in the murine model. Female mice of the Balb / c strain were infected with cercariae and treated intraperitoneally with 3 doses of 100 μg of the proteins at 10 day intervals from the 28th day of infection. Egg numbers were counted in the feces on the 48th and 54th days after infection by the Kato-Katz method. On the 55th day after infection, adult worms were retaken from the hepatic and mesenteric intestinal system, global and differential counts of LCP and blood cells. Cytokines IFN-γ, IL-4 and IL-10 in plasma were also quantified, as well as the production of antibodies of the IgG2a and IgE classes. For the analysis of the granulomas and deposition of collagen histological laminae of the liver were made. Our results demonstrate that treatment with the HGPRT enzyme appears to stimulate the production of IL-4 and IL-10 cytokines and promoted significant reduction of liver granulomas in infected and treated animals. Treatment with the PNP enzyme was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine. The PNP and MIX enzyme treatment were able to reduce the number of eggs in the faeces and negatively modulate the number of eosinophils in the PCL and in the blood. Therefore, treatment with the recombinant enzymes of S. mansoni HGPRT and PNP seems to contribute to the control and reduction of pathophysiological aspects of schistosomiasis, contributing to the reduction of morbidity associated with schistosomiasis in the murine model.A esquistossomose é uma doença que atinge um elevado número de pessoas em 78 países. O número de casos aumentou nos últimos anos e não há vacina e novos fármacos, aspecto preocupante, uma vez que há perda de sensibilidade ao medicamento utilizado, o Praziquantel. O presente estudo buscou avaliar os efeitos das enzimas recombinantes de S. mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) e o MIX das duas enzimas no tratamento da esquistossomose no modelo murino. Camundongos fêmeas da linhagem Balb/c foram infectadas com cercárias e tratadas via intraperitoneal com 3 doses de 100 μg das proteínas em intervalos de 10 dias a partir do 28º dia de infecção. Foram contados números de ovos nas fezes no 48ª e 54º dia após a infecção pelo método Kato-Katz. No 55º dia após a infecção foram recuperados vermes adultos do sistema porta-hepático e mesentérico intestinal, contagem global e diferencial de células do LCP e do sangue. Também foram quantificadas as citocinas IFN-γ, IL-4 e IL-10 no plasma, assim como a produção de anticorpos das classes IgG2a e IgE. Para a análise dos granulomas e deposição de colágeno foram confeccionadas lâminas histológicas do fígado. Nossos resultados demonstram que o tratamento com a enzima HGPRT parece estimular a produção das citocinas IL-4 e IL-10 e promoveu redução significativa de granulomas no fígado dos animais infectados e tratados. O tratamento com a enzima PNP foi capaz de reduzir o número de vermes no fígado e nos vasos mesentéricos do intestino. Já o tratamento com a enzima PNP e o MIX foram capazes de reduzir o número de ovos nas fezes e modular negativamente o número de eosinófilos no LCP e no sangue. Portanto, o tratamento com as enzimas recombinantes de S. mansoni HGPRT e PNP parece contribuir para o controle e redução dos aspectos fisiopatológicos da esquistossomose, contribuindo com a diminuição da morbidade associada a esquistossomose no modelo murino.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: Código de Financiamento 001porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarImunoterapiaHipoxantina-Guanina Fosforibosiltransferase (HGPRT)Purina Nucleosil Fosforilase (PNP)ImmunotherapyHypoxanthine-Guanine Phosphoribosyltransferase (HGPRT)Purine Nucleosil Phosphorylase (PNP)CIENCIAS BIOLOGICAS::GENETICACIENCIAS BIOLOGICAS::IMUNOLOGIACIENCIAS BIOLOGICAS::PARASITOLOGIAEfeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimentalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis24 meses após a data da defesa600600d0b619ca-16cf-40f9-9e9b-1792083fa39finfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALFragelli, B. D. L. Dissertação.pdfFragelli, B. D. L. Dissertação.pdfapplication/pdf3339313https://repositorio.ufscar.br/bitstream/ufscar/10614/1/Fragelli%2c%20B.%20D.%20L.%20Disserta%c3%a7%c3%a3o.pdf217cc2f7bdc9803248428e9d56f6460fMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/10614/3/license.txtae0398b6f8b235e40ad82cba6c50031dMD53TEXTFragelli, B. D. L. Dissertação.pdf.txtFragelli, B. D. L. Dissertação.pdf.txtExtracted texttext/plain193416https://repositorio.ufscar.br/bitstream/ufscar/10614/4/Fragelli%2c%20B.%20D.%20L.%20Disserta%c3%a7%c3%a3o.pdf.txt231579599e68e0b4e877c6d155f74497MD54THUMBNAILFragelli, B. D. L. Dissertação.pdf.jpgFragelli, B. D. L. 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dc.title.por.fl_str_mv Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
title Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
spellingShingle Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
Fragelli, Bruna Dias de Lima
Imunoterapia
Hipoxantina-Guanina Fosforibosiltransferase (HGPRT)
Purina Nucleosil Fosforilase (PNP)
Immunotherapy
Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT)
Purine Nucleosil Phosphorylase (PNP)
CIENCIAS BIOLOGICAS::GENETICA
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS BIOLOGICAS::PARASITOLOGIA
title_short Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
title_full Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
title_fullStr Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
title_full_unstemmed Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
title_sort Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental
author Fragelli, Bruna Dias de Lima
author_facet Fragelli, Bruna Dias de Lima
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/0149534142066009
dc.contributor.author.fl_str_mv Fragelli, Bruna Dias de Lima
dc.contributor.advisor1.fl_str_mv Anibal, Fernanda de Freitas
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4918261968772806
dc.contributor.advisor-co1.fl_str_mv Pereira, Humberto D'Muniz
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/8681619250791832
dc.contributor.authorID.fl_str_mv 05291ea2-5ffb-48c9-aec4-e79b88348c0e
contributor_str_mv Anibal, Fernanda de Freitas
Pereira, Humberto D'Muniz
dc.subject.por.fl_str_mv Imunoterapia
Hipoxantina-Guanina Fosforibosiltransferase (HGPRT)
Purina Nucleosil Fosforilase (PNP)
topic Imunoterapia
Hipoxantina-Guanina Fosforibosiltransferase (HGPRT)
Purina Nucleosil Fosforilase (PNP)
Immunotherapy
Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT)
Purine Nucleosil Phosphorylase (PNP)
CIENCIAS BIOLOGICAS::GENETICA
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS BIOLOGICAS::PARASITOLOGIA
dc.subject.eng.fl_str_mv Immunotherapy
Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT)
Purine Nucleosil Phosphorylase (PNP)
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::GENETICA
CIENCIAS BIOLOGICAS::IMUNOLOGIA
CIENCIAS BIOLOGICAS::PARASITOLOGIA
description Schistosomiasis is a disease that affects a large number of people in 78 countries. The number of cases has increased in recent years and there is no vaccine and new drugs, a worrying aspect, since there is loss of sensitivity to the drug used, Praziquantel. The present study aimed to evaluate the effects of the recombinant enzymes of S. mansoni Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) and Purine Nucleoside Phosphorylase (PNP) and the MIX of the two enzymes in the treatment of schistosomiasis in the murine model. Female mice of the Balb / c strain were infected with cercariae and treated intraperitoneally with 3 doses of 100 μg of the proteins at 10 day intervals from the 28th day of infection. Egg numbers were counted in the feces on the 48th and 54th days after infection by the Kato-Katz method. On the 55th day after infection, adult worms were retaken from the hepatic and mesenteric intestinal system, global and differential counts of LCP and blood cells. Cytokines IFN-γ, IL-4 and IL-10 in plasma were also quantified, as well as the production of antibodies of the IgG2a and IgE classes. For the analysis of the granulomas and deposition of collagen histological laminae of the liver were made. Our results demonstrate that treatment with the HGPRT enzyme appears to stimulate the production of IL-4 and IL-10 cytokines and promoted significant reduction of liver granulomas in infected and treated animals. Treatment with the PNP enzyme was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine. The PNP and MIX enzyme treatment were able to reduce the number of eggs in the faeces and negatively modulate the number of eosinophils in the PCL and in the blood. Therefore, treatment with the recombinant enzymes of S. mansoni HGPRT and PNP seems to contribute to the control and reduction of pathophysiological aspects of schistosomiasis, contributing to the reduction of morbidity associated with schistosomiasis in the murine model.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-10-25T17:28:24Z
dc.date.available.fl_str_mv 2018-10-25T17:28:24Z
dc.date.issued.fl_str_mv 2018-02-26
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dc.identifier.citation.fl_str_mv FRAGELLI, Bruna Dias de Lima. Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10614.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/10614
identifier_str_mv FRAGELLI, Bruna Dias de Lima. Efeito das enzimas recombinantes de Schistosoma mansoni Hipoxantina-Guanina Fosforibosiltransferase (HGPRT) e Purina Nucleosídeo Fosforilase (PNP) no tratamento da esquistossomose experimental. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10614.
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Câmpus São Carlos
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