Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/16333 |
Resumo: | Parkinsonism is a neurological syndrome characterized by resting tremor, stiffness in cogwheels, postural instability and bradykinesia. Parkinson's disease (PD) is the second most common neurodegenerative disease and the leading cause of parkinsonism, accounting for 80% of cases. It is the second most prevalent movement disorder. Neuroinflammation and the increase of serum inflammatory cytokines have been associated with the disease. As several studies have shown that antidepressant drugs decrease serum proinflammatory cytokines in animal models of PD and improve the motor symptoms of selected patients, we investigated whether adjuvant therapy with duloxetine decreases peripheral levels of inflammatory cytokines and motor symptoms in PD patients without other chronic inflammatory diseases. This open, non-randomized, non-placebo controlled clinical trial was conducted at the Santa Maria University Hospital with the objective of assessing whether 8 weeks of adjuvant therapy with duloxetine improved the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr modified (HY) and PDQ-39 (Parkinson Disease Quality of Life Questionnaire) in 17 patients with PD. Serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and interleukin 10 (IL-10) were determined before and after 4 and 8 weeks of pharmacological intervention. There were no withdrawals during the study. Duloxetine significantly improved motor symptoms, activities of daily living and quality of life in patients with PD. Ten patients presented a decrease of 5 points (or more) in the UPDRS scores, being arbitrarily classified as responders. The therapeutic response was predicted by the logistic regression of the clinical parameters in the recruitment, being a score of HY of at least 2 more important. While serum levels of IL-6, IL-1β and TNF-α decreased, IL-10 levels increased at the end of the pharmacological intervention. We conclude that duloxetine improves the clinical and inflammatory profile of patients with PD. We suggest that adjuvant therapy with duloxetine may bring additional benefits to selected PD patients. |
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2019-04-29T14:50:32Z2019-04-29T14:50:32Z2019-03-22http://repositorio.ufsm.br/handle/1/16333Parkinsonism is a neurological syndrome characterized by resting tremor, stiffness in cogwheels, postural instability and bradykinesia. Parkinson's disease (PD) is the second most common neurodegenerative disease and the leading cause of parkinsonism, accounting for 80% of cases. It is the second most prevalent movement disorder. Neuroinflammation and the increase of serum inflammatory cytokines have been associated with the disease. As several studies have shown that antidepressant drugs decrease serum proinflammatory cytokines in animal models of PD and improve the motor symptoms of selected patients, we investigated whether adjuvant therapy with duloxetine decreases peripheral levels of inflammatory cytokines and motor symptoms in PD patients without other chronic inflammatory diseases. This open, non-randomized, non-placebo controlled clinical trial was conducted at the Santa Maria University Hospital with the objective of assessing whether 8 weeks of adjuvant therapy with duloxetine improved the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr modified (HY) and PDQ-39 (Parkinson Disease Quality of Life Questionnaire) in 17 patients with PD. Serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and interleukin 10 (IL-10) were determined before and after 4 and 8 weeks of pharmacological intervention. There were no withdrawals during the study. Duloxetine significantly improved motor symptoms, activities of daily living and quality of life in patients with PD. Ten patients presented a decrease of 5 points (or more) in the UPDRS scores, being arbitrarily classified as responders. The therapeutic response was predicted by the logistic regression of the clinical parameters in the recruitment, being a score of HY of at least 2 more important. While serum levels of IL-6, IL-1β and TNF-α decreased, IL-10 levels increased at the end of the pharmacological intervention. We conclude that duloxetine improves the clinical and inflammatory profile of patients with PD. We suggest that adjuvant therapy with duloxetine may bring additional benefits to selected PD patients.Parkinsonismo é uma síndrome neurológica que se caracteriza pela presença de tremor de repouso, rigidez em roda denteada, instabilidade postural e bradicinesia. A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum e a principal causa de parkinsonismo, representando 80% dos casos. É o segundo transtorno do movimento mais prevalente. A neuroinflamação e o aumento das citocinas inflamatórias séricas têm sido associados à doença. Como diversos estudos mostram que medicamentos antidepressivos diminuem as citocinas pró-inflamatórias séricas em modelos animais de DP e melhoram os sintomas motores de pacientes selecionados, investigamos se a terapia adjuvante com duloxetina diminui os níveis periféricos de citocinas inflamatórias e os sintomas motores em pacientes com DP sem outras doenças inflamatórias crônicas. Este ensaio clínico aberto, não randomizado, não controlado por placebo, foi realizado no Hospital Universitário de Santa Maria (HUSM) com o objetivo de avaliar se 8 semanas de terapia adjuvante com duloxetina melhoravam a Escala de Avaliação de Doença de Parkinson Unificada (UPDRS), a escala de Hoehn e Yahr modificada (HY) e PDQ-39 (Parkinson Disease Quality of Life Questionnaire) em 17 pacientes com DP. Os níveis séricos de fator de necrose tumoral alfa (TNF-α), interleucina 1 beta (IL-1β), interleucina 6 (IL-6) e interleucina 10 (IL-10) foram determinados antes e após 4 e 8 semanas de intervenção farmacológica. Não houve desistências durante o estudo. A duloxetina melhorou estatisticamente os sintomas motores, as atividades de vida diária e a qualidade de vida em pacientes com DP. Dez pacientes apresentaram um decréscimo de 5 pontos (ou mais) dos escores da UPDRS, sendo arbitrariamente classificados como respondedores. A resposta terapêutica foi predita pela regressão logística dos parâmetros clínicos no recrutamento, sendo um escore de HY de pelo menos 2 o mais importante. Enquanto os níveis séricos de IL-6, IL-1β e TNF-α diminuíram, os níveis de IL-10 aumentaram no final da intervenção farmacológica. Concluimos que a duloxetina melhora o perfil clínico e inflamatório de pacientes com DP. Sugerimos que a terapia adjuvante com duloxetina pode trazer benefícios adicionais para pacientes com DP selecionados.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessParkinsonismoUPDRSNeuroinflamaçãoISRSIRSNParkinsonismNeuroinflammationSSRISNRICNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAEfeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo abertoEffect of Duloxetine administration on inflammatory cytokines and motor symptoms in patients with Parkinson disease - open studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMello, Carlos Fernando dehttp://lattes.cnpq.br/3913887223894236Fagundes, Renato Borgeshttp://lattes.cnpq.br/5255286815018611Fighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231http://lattes.cnpq.br/8252333960226539Silveira, Juliana Oliveira Freitas20100000000060082e537b0-4a43-400e-9f82-0cd91952adea6ecd4828-cfef-402d-841c-7e9847088572acd74c2e-f7a4-445b-bfdf-8e4c1d552196f64f9f4e-453c-4815-b387-e5d934f164f9reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGFARMACOLOGIA_2019_SILVEIRA_JULIANA.pdfDIS_PPGFARMACOLOGIA_2019_SILVEIRA_JULIANA.pdfDissertação de Mestradoapplication/pdf882731http://repositorio.ufsm.br/bitstream/1/16333/1/DIS_PPGFARMACOLOGIA_2019_SILVEIRA_JULIANA.pdf31681d27bfaa571fcf3553a397755997MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
dc.title.alternative.eng.fl_str_mv |
Effect of Duloxetine administration on inflammatory cytokines and motor symptoms in patients with Parkinson disease - open study |
title |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
spellingShingle |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto Silveira, Juliana Oliveira Freitas Parkinsonismo UPDRS Neuroinflamação ISRS IRSN Parkinsonism Neuroinflammation SSRI SNRI CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
title_full |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
title_fullStr |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
title_full_unstemmed |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
title_sort |
Efeito da administração de Duloxetina sobre citocinas inflamatórias e sintomas motores em pacientes com doença de Parkinson – estudo aberto |
author |
Silveira, Juliana Oliveira Freitas |
author_facet |
Silveira, Juliana Oliveira Freitas |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Mello, Carlos Fernando de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3913887223894236 |
dc.contributor.referee1.fl_str_mv |
Fagundes, Renato Borges |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/5255286815018611 |
dc.contributor.referee2.fl_str_mv |
Fighera, Michele Rechia |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8583392747509231 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8252333960226539 |
dc.contributor.author.fl_str_mv |
Silveira, Juliana Oliveira Freitas |
contributor_str_mv |
Mello, Carlos Fernando de Fagundes, Renato Borges Fighera, Michele Rechia |
dc.subject.por.fl_str_mv |
Parkinsonismo UPDRS Neuroinflamação ISRS IRSN |
topic |
Parkinsonismo UPDRS Neuroinflamação ISRS IRSN Parkinsonism Neuroinflammation SSRI SNRI CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Parkinsonism Neuroinflammation SSRI SNRI |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Parkinsonism is a neurological syndrome characterized by resting tremor, stiffness in cogwheels, postural instability and bradykinesia. Parkinson's disease (PD) is the second most common neurodegenerative disease and the leading cause of parkinsonism, accounting for 80% of cases. It is the second most prevalent movement disorder. Neuroinflammation and the increase of serum inflammatory cytokines have been associated with the disease. As several studies have shown that antidepressant drugs decrease serum proinflammatory cytokines in animal models of PD and improve the motor symptoms of selected patients, we investigated whether adjuvant therapy with duloxetine decreases peripheral levels of inflammatory cytokines and motor symptoms in PD patients without other chronic inflammatory diseases. This open, non-randomized, non-placebo controlled clinical trial was conducted at the Santa Maria University Hospital with the objective of assessing whether 8 weeks of adjuvant therapy with duloxetine improved the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr modified (HY) and PDQ-39 (Parkinson Disease Quality of Life Questionnaire) in 17 patients with PD. Serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and interleukin 10 (IL-10) were determined before and after 4 and 8 weeks of pharmacological intervention. There were no withdrawals during the study. Duloxetine significantly improved motor symptoms, activities of daily living and quality of life in patients with PD. Ten patients presented a decrease of 5 points (or more) in the UPDRS scores, being arbitrarily classified as responders. The therapeutic response was predicted by the logistic regression of the clinical parameters in the recruitment, being a score of HY of at least 2 more important. While serum levels of IL-6, IL-1β and TNF-α decreased, IL-10 levels increased at the end of the pharmacological intervention. We conclude that duloxetine improves the clinical and inflammatory profile of patients with PD. We suggest that adjuvant therapy with duloxetine may bring additional benefits to selected PD patients. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-04-29T14:50:32Z |
dc.date.available.fl_str_mv |
2019-04-29T14:50:32Z |
dc.date.issued.fl_str_mv |
2019-03-22 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/16333 |
url |
http://repositorio.ufsm.br/handle/1/16333 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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