AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE
Ano de defesa: | 2021 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Estadual do Centro-Oeste
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Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG)
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Departamento: |
Unicentro::Departamento de Farmácia
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País: |
Brasil
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Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede.unicentro.br:8080/jspui/handle/jspui/1753 |
Resumo: | Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory diseases that primarily involves the joints and may include extra-articular manifestations such as nodules, pulmonary involvement, vasculitis, and systemic comorbidities. Regarding inflammatory symptoms, joint swelling is caused by inflammation of the synovial membrane due to activation of the immune system, characterized by infiltration of leukocytes. Pterostilbene (PTE) can be found in blueberries and grapes, from plants belonging to the Vitis and Vaccinium families. It has anti-hypertensive activities; anticancer; antihypercholesterolemic; antidiabetics; antioxidants and anti-inflammatory. The aim of this project was to verify if pterostilbene has superior activity, as well as the basic mechanism of action of resveratrol. The drug was suspended in carboxymethylcellulose (CMC) (1%) at different concentrations (4 mg/kg; 200 mg/kg; 400 mg/kg) to be administered orally. Forty-five rats of the Rattus Norvegicus breed, Wistar lineage were used, the animals were divided into 3 groups with a group with 5, another 10 and another with 30 rats, corresponding, respectively, to the Control Group (CG); SHAM Group (SHAM) and Pterostilbene Group (GP), the SHAM and GP groups were subdivided into: with joint damage, and with and without treatment with an oral solution of Pterostilbene; groups were subdivided into 0 (with euthanasia 12 hours after induction) and 3 days (with euthanasia 72 hours after). Histological analyzes were performed to evaluate the pathological aspects, observing the characteristics of the epithelial changes and inflammatory infiltrate, type, and a number of cells, in addition to neovascularization and fibroblasts. Analyzes of inflammatory cytokines by flow cytometry were also performed. An acute inflammatory process, diffusely with mild to moderate intensity, characterizes lesions. In the 12h histological sections, it was observed that the treated groups presented a mild amount of mononuclear inflammatory cells (MN) and a moderate amount of polymorphonuclear cells (PM). It was also observed proliferative phenomena of an increasing form of fibroblasts up to the group treated with 400 mg/kg. In the 72h sections, it was observed that the groups treated with 4 mg/kg and 400 mg/kg presented moderate levels of PM, and light concentration of MN. At 200 mg/kg, there was a moderate concentration for both cell forms. Regarding neovascularization, it was observed that in all groups there was a mild process of angiogenesis As for the analysis by flow cytometry, the analyzes were divided by the data from the Th1/Th2 kit and the inflammation kit. In the Th1/Th2 analyses, the levels of tumor necrosis factor (TNF) were slightly increased, as is characteristic of RA, and due to the MN that are involved in the process of stimulating the production of TNF in the Th1 pathway. In the levels of interferon-γ (IFN-γ), there was a slight increase corroborating the histology where MN that induce its production was found. Interleukin (IL) 2 levels increased in concentrations in the 12h and 72h groups, with the exception of GP1, in relation to the initial 0h assessment; it can be explained due to stimulated production by T cells and IL-12 levels. IL-4 was increased in all groups compared to the initial assessment and the treatment may have provided an increase in this IL in groups treated with the highest concentrations of PTE after 72 hours of injury. IL-5 values were decreased in all groups compared to control, and having an increase in groups GP50 and GP100 72h in relation to the initial values (0h); the lowest levels found may be due to inhibition by IFN. In the analysis with inflammation kit, it was observed that TNF levels were increased because cells such as macrophages and neutrophils would be involved in the production process. IFN-γ levels increased in all treated groups compared to control; they may be related to the stimulation made by IL-12 and MN. IL-6 was also increased in all treated groups compared to control and is linked to the promotion and maturation of inflammatory cells. IL-12p70 levels increased in concentrations both in the 12h and 72h groups in relation to the initial 0h assessment and to the control; the increased levels are expected in RA as it participates in the Th1 pathway activation cascade. IL-10 levels increased slightly in all treated groups compared to the control, its levels may be due to the probable inhibition of its production, which may occur by the action of IL-10 itself, IL-4, and IFN-γ. The levels of monocyte chemotactic protein (MCP)-1 increased in all treated groups compared to control; with a significant increase in the group treated with 400 mg/kg corroborating the histology that presented an intense amount of fibroblasts after 72h. It is concluded that Pterostilbene, by having a proven anti-inflammatory activity, promoted a balance in the inflammatory process seen by the concentration of the evaluated interleukins, their activities, and correlations with a tendency of efficient inflammatory control so that there is no exacerbation of symptoms and lesions; in addition to stimulating structural restoration through the high production of fibroblasts and angiogenesis. |
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Oliveira, Paulo Renato dehttp://lattes.cnpq.br/3167101952781896083.262.739-96http://lattes.cnpq.br/0729686687578360Hosni, Andressa Panegalli2021-11-22T15:28:58Z2021-02-19Hosni, Andressa Panegalli. AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE. 2021. 69 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado - Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.http://tede.unicentro.br:8080/jspui/handle/jspui/1753Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory diseases that primarily involves the joints and may include extra-articular manifestations such as nodules, pulmonary involvement, vasculitis, and systemic comorbidities. Regarding inflammatory symptoms, joint swelling is caused by inflammation of the synovial membrane due to activation of the immune system, characterized by infiltration of leukocytes. Pterostilbene (PTE) can be found in blueberries and grapes, from plants belonging to the Vitis and Vaccinium families. It has anti-hypertensive activities; anticancer; antihypercholesterolemic; antidiabetics; antioxidants and anti-inflammatory. The aim of this project was to verify if pterostilbene has superior activity, as well as the basic mechanism of action of resveratrol. The drug was suspended in carboxymethylcellulose (CMC) (1%) at different concentrations (4 mg/kg; 200 mg/kg; 400 mg/kg) to be administered orally. Forty-five rats of the Rattus Norvegicus breed, Wistar lineage were used, the animals were divided into 3 groups with a group with 5, another 10 and another with 30 rats, corresponding, respectively, to the Control Group (CG); SHAM Group (SHAM) and Pterostilbene Group (GP), the SHAM and GP groups were subdivided into: with joint damage, and with and without treatment with an oral solution of Pterostilbene; groups were subdivided into 0 (with euthanasia 12 hours after induction) and 3 days (with euthanasia 72 hours after). Histological analyzes were performed to evaluate the pathological aspects, observing the characteristics of the epithelial changes and inflammatory infiltrate, type, and a number of cells, in addition to neovascularization and fibroblasts. Analyzes of inflammatory cytokines by flow cytometry were also performed. An acute inflammatory process, diffusely with mild to moderate intensity, characterizes lesions. In the 12h histological sections, it was observed that the treated groups presented a mild amount of mononuclear inflammatory cells (MN) and a moderate amount of polymorphonuclear cells (PM). It was also observed proliferative phenomena of an increasing form of fibroblasts up to the group treated with 400 mg/kg. In the 72h sections, it was observed that the groups treated with 4 mg/kg and 400 mg/kg presented moderate levels of PM, and light concentration of MN. At 200 mg/kg, there was a moderate concentration for both cell forms. Regarding neovascularization, it was observed that in all groups there was a mild process of angiogenesis As for the analysis by flow cytometry, the analyzes were divided by the data from the Th1/Th2 kit and the inflammation kit. In the Th1/Th2 analyses, the levels of tumor necrosis factor (TNF) were slightly increased, as is characteristic of RA, and due to the MN that are involved in the process of stimulating the production of TNF in the Th1 pathway. In the levels of interferon-γ (IFN-γ), there was a slight increase corroborating the histology where MN that induce its production was found. Interleukin (IL) 2 levels increased in concentrations in the 12h and 72h groups, with the exception of GP1, in relation to the initial 0h assessment; it can be explained due to stimulated production by T cells and IL-12 levels. IL-4 was increased in all groups compared to the initial assessment and the treatment may have provided an increase in this IL in groups treated with the highest concentrations of PTE after 72 hours of injury. IL-5 values were decreased in all groups compared to control, and having an increase in groups GP50 and GP100 72h in relation to the initial values (0h); the lowest levels found may be due to inhibition by IFN. In the analysis with inflammation kit, it was observed that TNF levels were increased because cells such as macrophages and neutrophils would be involved in the production process. IFN-γ levels increased in all treated groups compared to control; they may be related to the stimulation made by IL-12 and MN. IL-6 was also increased in all treated groups compared to control and is linked to the promotion and maturation of inflammatory cells. IL-12p70 levels increased in concentrations both in the 12h and 72h groups in relation to the initial 0h assessment and to the control; the increased levels are expected in RA as it participates in the Th1 pathway activation cascade. IL-10 levels increased slightly in all treated groups compared to the control, its levels may be due to the probable inhibition of its production, which may occur by the action of IL-10 itself, IL-4, and IFN-γ. The levels of monocyte chemotactic protein (MCP)-1 increased in all treated groups compared to control; with a significant increase in the group treated with 400 mg/kg corroborating the histology that presented an intense amount of fibroblasts after 72h. It is concluded that Pterostilbene, by having a proven anti-inflammatory activity, promoted a balance in the inflammatory process seen by the concentration of the evaluated interleukins, their activities, and correlations with a tendency of efficient inflammatory control so that there is no exacerbation of symptoms and lesions; in addition to stimulating structural restoration through the high production of fibroblasts and angiogenesis.A artrite reumatoide (AR) é uma das doenças inflamatórias crônicas mais prevalentes e que envolve primeiramente as articulações e pode incluir também manifestações extra articulares como nódulos, envolvimento pulmonar, vasculite e comorbidades sistêmicas. Com relação aos sintomas inflamatórios, o inchaço articular se dá pela inflamação da membrana sinovial devido a ativação do sistema imune, caracterizada pela infiltração de leucócitos. O pterostilbeno (PTE) pode ser encontrado em mirtilos e uvas, de plantas pertencentes às famílias Vitis e Vaccinium. Apresenta atividades anti-hipertensivas; anticancerígenas; anti-hipercolesterolêmicas; antidiabéticas; antioxidantes e anti-inflamatórias. O objetivo do presente projeto foi verificar se o pterostilbeno apresenta atividade superior, bem como o mecanismo básico de ação do resveratrol. O fármaco foi suspenso em carboximetilcelulose (CMC) (1%) em diferentes concentrações (4 mg/kg; 200 mg/kg; 400 mg/kg) para ser administrado via oral. Foram utilizados 45 ratos da raça Rattus Norvegicus, linhagem Wistar, os animais foram divididos em 3 grupos com um grupo com 5, outro 10 e outro com 30 ratos correspondendo, respectivamente, ao Grupo Controle (GC); Grupo SHAM (SHAM) e o Grupo Pterostilbeno (GP), os grupos SHAM e GP foram subdivididos em: com lesão articular, e com e sem tratamento com solução oral de Pterostilbeno; os grupos foram subdivididos em 0 (com eutanásia 12 horas após a indução) e 3 dias (com eutanásia 72 horas após). Foram realizadas análises histológicas para avaliar os aspectos anatomopatológicos observando as características das alterações epiteliais e do infiltrado inflamatório, tipo e quantidade de células, além de neovascularização e fibroblastos. Foram realizadas também análises das citocinas inflamatórias por citometria de fluxo. As lesões caracterizam-se por um processo inflamatório agudo, de forma difusa com intensidade leve à moderada. Nos cortes histológicos 12h, foi observado que os grupos tratados apresentaram uma quantidade leve de células inflamatórias mononucleadas (MN) e quantidade moderada de células polimorfonucleares (PM). Observou-se também fenômenos proliferativos de forma crescente de fibroblastos até o grupo tratado com 400 mg/kg. Nos cortes de 72h observou-se que os grupos tratados com 4 mg/kg e 400 mg/kg apresentaram nível moderado de PM, e concentração leve de MN. Já com 200 mg/kg, houve concentração moderada para ambas as formas celulares. Com relação a neovascularização observou-se que em todos os grupos ocorreu um processo de angiogênese de forma leve Quanto a análise por citometria de fluxo, as análises foram divididas pelos dados dos kit Th1/Th2 e do inflammation. Nas análises com o Th1/Th2 os níveis de fator de necrose tumoral (TNF) estavam levemente aumentados, como é característico da AR, e devido as MN que estão envolvidas no processo de estímulo da produção de TNF na via Th1. Nos níveis de interferon-γ (IFN-γ) houve um leve aumento corroborando com a histologia onde foram encontradas MN que induzem a sua produção. Os níveis de interleucina (IL) 2 sofreram um aumento nas concentrações nos grupos de 12h e 72h, com exceção do GP1, em relação à avaliação inicial 0h; podendo ser explicada devido à produção estimulada pelas células T e dos níveis de IL-12. A IL-4 estava aumentada em todos os grupos em relação a avaliação inicial e o tratamento pode ter proporcionado um aumento dessa IL nos grupos tratados com as maiores concentrações de PTE após 72h da lesão. Os valores de IL-5 estavam diminuídos em todos os grupos em relação ao controle; e tendo um aumento nos grupos GP50 e GP100 72h em relação aos valores iniciais (0h); os níveis mais baixos encontrados podem ser devido a inibição pelo IFN. Já nas análises com o inflammation observou-se que os níveis de TNF estavam aumentados devido a células como macrófagos e neutrófilos estariam envolvidos no processo de produção. Os níveis de IFN-γ tiveram aumento em todos os grupos tratados em relação ao controle; podendo ser relacionados com a estimulação feita pela IL-12 e MN. A IL-6 também estava aumentada em todos os grupos tratados em relação ao controle e está ligada com a promoção e maturação de células inflamatórias. Os níveis de IL-12p70 sofreram um aumento nas concentrações tanto nos grupos de 12h como nos de 72h em relação à avaliação inicial 0h e ao controle; os níveis aumentados é o esperado na AR pois ela participa da cascata de ativação da via Th1. Os níveis de IL-10 aumentaram levemente em todos os grupos tratados em relação ao controle, os seus níveis podem ser devido à provável inibição de sua produção que pode ocorrer pela ação da própria IL-10, da IL-4 e IFN-γ. Já os níveis da proteína quimiotática de monócitos (MCP)-1 tiveram aumento em todos os grupos tratados em relação ao controle; com um aumento significativo no grupo tratado com 400 mg/kg corroborando com a histologia o qual apresentou uma intensa quantidade de fibroblastos após 72h. Conclui-se que o Pterostilbeno, ao possuir uma atividade anti-inflamatória comprovada, promoveu um equilíbrio no processo inflamatório visto pela concentração das interleucinas avaliadas, suas atividades e correlações com uma tendência de controle inflamatório eficiente para não ocorrer uma exacerbação dos sintomas e lesões; além de estimular a restauração estrutural pela alta produção de fibroblastos e angiogênese.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2021-11-22T15:28:58Z No. of bitstreams: 1 dissertação ANDRESSA PANEGALLI HOSNI.pdf: 2922011 bytes, checksum: b25fff332e00f6dc9b783af813f73d2e (MD5)Made available in DSpace on 2021-11-22T15:28:58Z (GMT). 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dc.title.por.fl_str_mv |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
title |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
spellingShingle |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE Hosni, Andressa Panegalli Articulação do joelho Artrite experimental Artrite reumatoide Inflamação Citometria de fluxo Citocinas Knee joint Experimental Arthritis Rheumatoid Arthritis Inflammation Flow Cytometry Cytokines CIENCIAS DA SAUDE::FARMACIA |
title_short |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
title_full |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
title_fullStr |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
title_full_unstemmed |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
title_sort |
AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE |
author |
Hosni, Andressa Panegalli |
author_facet |
Hosni, Andressa Panegalli |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Paulo Renato de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3167101952781896 |
dc.contributor.authorID.fl_str_mv |
083.262.739-96 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0729686687578360 |
dc.contributor.author.fl_str_mv |
Hosni, Andressa Panegalli |
contributor_str_mv |
Oliveira, Paulo Renato de |
dc.subject.por.fl_str_mv |
Articulação do joelho Artrite experimental Artrite reumatoide Inflamação Citometria de fluxo Citocinas |
topic |
Articulação do joelho Artrite experimental Artrite reumatoide Inflamação Citometria de fluxo Citocinas Knee joint Experimental Arthritis Rheumatoid Arthritis Inflammation Flow Cytometry Cytokines CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Knee joint Experimental Arthritis Rheumatoid Arthritis Inflammation Flow Cytometry Cytokines |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
description |
Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory diseases that primarily involves the joints and may include extra-articular manifestations such as nodules, pulmonary involvement, vasculitis, and systemic comorbidities. Regarding inflammatory symptoms, joint swelling is caused by inflammation of the synovial membrane due to activation of the immune system, characterized by infiltration of leukocytes. Pterostilbene (PTE) can be found in blueberries and grapes, from plants belonging to the Vitis and Vaccinium families. It has anti-hypertensive activities; anticancer; antihypercholesterolemic; antidiabetics; antioxidants and anti-inflammatory. The aim of this project was to verify if pterostilbene has superior activity, as well as the basic mechanism of action of resveratrol. The drug was suspended in carboxymethylcellulose (CMC) (1%) at different concentrations (4 mg/kg; 200 mg/kg; 400 mg/kg) to be administered orally. Forty-five rats of the Rattus Norvegicus breed, Wistar lineage were used, the animals were divided into 3 groups with a group with 5, another 10 and another with 30 rats, corresponding, respectively, to the Control Group (CG); SHAM Group (SHAM) and Pterostilbene Group (GP), the SHAM and GP groups were subdivided into: with joint damage, and with and without treatment with an oral solution of Pterostilbene; groups were subdivided into 0 (with euthanasia 12 hours after induction) and 3 days (with euthanasia 72 hours after). Histological analyzes were performed to evaluate the pathological aspects, observing the characteristics of the epithelial changes and inflammatory infiltrate, type, and a number of cells, in addition to neovascularization and fibroblasts. Analyzes of inflammatory cytokines by flow cytometry were also performed. An acute inflammatory process, diffusely with mild to moderate intensity, characterizes lesions. In the 12h histological sections, it was observed that the treated groups presented a mild amount of mononuclear inflammatory cells (MN) and a moderate amount of polymorphonuclear cells (PM). It was also observed proliferative phenomena of an increasing form of fibroblasts up to the group treated with 400 mg/kg. In the 72h sections, it was observed that the groups treated with 4 mg/kg and 400 mg/kg presented moderate levels of PM, and light concentration of MN. At 200 mg/kg, there was a moderate concentration for both cell forms. Regarding neovascularization, it was observed that in all groups there was a mild process of angiogenesis As for the analysis by flow cytometry, the analyzes were divided by the data from the Th1/Th2 kit and the inflammation kit. In the Th1/Th2 analyses, the levels of tumor necrosis factor (TNF) were slightly increased, as is characteristic of RA, and due to the MN that are involved in the process of stimulating the production of TNF in the Th1 pathway. In the levels of interferon-γ (IFN-γ), there was a slight increase corroborating the histology where MN that induce its production was found. Interleukin (IL) 2 levels increased in concentrations in the 12h and 72h groups, with the exception of GP1, in relation to the initial 0h assessment; it can be explained due to stimulated production by T cells and IL-12 levels. IL-4 was increased in all groups compared to the initial assessment and the treatment may have provided an increase in this IL in groups treated with the highest concentrations of PTE after 72 hours of injury. IL-5 values were decreased in all groups compared to control, and having an increase in groups GP50 and GP100 72h in relation to the initial values (0h); the lowest levels found may be due to inhibition by IFN. In the analysis with inflammation kit, it was observed that TNF levels were increased because cells such as macrophages and neutrophils would be involved in the production process. IFN-γ levels increased in all treated groups compared to control; they may be related to the stimulation made by IL-12 and MN. IL-6 was also increased in all treated groups compared to control and is linked to the promotion and maturation of inflammatory cells. IL-12p70 levels increased in concentrations both in the 12h and 72h groups in relation to the initial 0h assessment and to the control; the increased levels are expected in RA as it participates in the Th1 pathway activation cascade. IL-10 levels increased slightly in all treated groups compared to the control, its levels may be due to the probable inhibition of its production, which may occur by the action of IL-10 itself, IL-4, and IFN-γ. The levels of monocyte chemotactic protein (MCP)-1 increased in all treated groups compared to control; with a significant increase in the group treated with 400 mg/kg corroborating the histology that presented an intense amount of fibroblasts after 72h. It is concluded that Pterostilbene, by having a proven anti-inflammatory activity, promoted a balance in the inflammatory process seen by the concentration of the evaluated interleukins, their activities, and correlations with a tendency of efficient inflammatory control so that there is no exacerbation of symptoms and lesions; in addition to stimulating structural restoration through the high production of fibroblasts and angiogenesis. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-22T15:28:58Z |
dc.date.issued.fl_str_mv |
2021-02-19 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Hosni, Andressa Panegalli. AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE. 2021. 69 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado - Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava-PR. |
dc.identifier.uri.fl_str_mv |
http://tede.unicentro.br:8080/jspui/handle/jspui/1753 |
identifier_str_mv |
Hosni, Andressa Panegalli. AVALIAÇÃO DO PTEROSTILBENO PARA TRATAMENTO NA FASE AGUDA DE ARTRITE REUMATOIDE. 2021. 69 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado - Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava-PR. |
url |
http://tede.unicentro.br:8080/jspui/handle/jspui/1753 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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600 600 600 600 |
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7775901432741191125 |
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6997636413449754996 |
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2075167498588264571 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Estadual do Centro-Oeste |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG) |
dc.publisher.initials.fl_str_mv |
UNICENTRO |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Unicentro::Departamento de Farmácia |
publisher.none.fl_str_mv |
Universidade Estadual do Centro-Oeste |
dc.source.none.fl_str_mv |
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