Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | https://tede2.pucrs.br/tede2/handle/tede/10754 |
Resumo: | Huntington?s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder. It is characterized by a neurobehavioral triad consisting of motor dysfunction, neuropsychiatric disturbance and cognitive decline. In HD the striatal neurons are degenerated leading to a decrease in dopamine D2 (D2R) and D1 (D1R), and adenosine A2A (A2AR) and A1 (A1R) leading to impaired movements such as chorea, bradykinesia, rigidity and locomotor incoordination. Furthermore, other molecular and biochemical mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation, neurodegeneration and changes in different neurotransmitter systems are involved in the pathophysiology of the disease. The 3-nitropropionic acid (3-NPA), a toxin derived from fungi and plants, can reproduce the behavioral phenotypes and biochemical alterations of HD. In the current study, we investigated the behavioral and morphological mechanisms in the brain and musculoskeletal system in adult zebrafish with 3-NPA-induced HD phenotype. For the biochemical and morphological analyses, adult zebrafish received a total of 7 intraperitoneal (i.p) injections (one injection every 4 days) of 3-NPA (60 mg/kg) for 28 days. On the 29th day, the brains were collected for histological, biochemical and molecular analyses. For the pharmacological modulation, on the 29th day after starting treatment, the animals receive a single i.p. injection of the following compounds: antioxidants, such as vitamin C (100 mg/kg); creatine (50 mg/kg) and melatonin (10 mg/kg); dopaminergic drugs, such as quinpirole (selective D2R agonist, 5 mg/kg) and eticlopride (selective D2R antagonist, 0.1 mg/kg); adenosinergic drugs such as CPA (selective A1R agonist, 1 mg/kg), CGS 21680 (selective A2AR agonist, 1 mg/kg), caffeine (non-selective antagonist of A1R e A2AR, 10 mg/kg), ZM 241385 (selective A2AR antagonist, 10 ?g/kg), DPCPX (selective A1R antagonist, 0.5 mg/kg), dipyridamole (nucleoside transporter inhibitor, 10 mg/kg), EHNA (adenosine deaminase inhibitor, 100 ?g/kg). After 30 min of i.p. injection, the locomotor activity and memory of the animals were evaluated. The histological results demonstrated that 3-NPA caused neurodegeneration and a decrease in granular cell in the brain tissue, but did not cause histological change in the cardiac and muscular tissue. Also, the results showed that there was not alteration in the TBARS and NPSH levels in the brain of adult zebrafish following 3-NPA treatment. Moreover, we observed that antioxidants vitamin C and creatine reversed the hypolocomotor effect induced by 3-NPA, while the memory deficit caused by 3-NPA was reversed by vitamin C and melatonin. Regarding the dopaminergic modulation, the 3-NPA caused decrease in dopamine, glutamate, and serotonin levels, but not did alter the gene expression of dopamine receptors. Also, the hypolocomotor effect and memory deficit induced by 3-NPA were reversed with quinpirole, but not with eticlopride. Caffeine and ZM 241385 reversed the hypolocomotor effect and memory deficit induced by 3-NPA, while the CGS 21680 potentiated the hypolocomotion and did not reverse the memory deficit induced by 3-NPA. In addition, CPA, DPCPX, dipyridamole and EHNA reversed the memory deficit induced by 3-NPA. Taken together, these data indicate that the 3-NPA treatment induces to behavioral phenotypes, histological and biochemical alterations as those observed in HD patients in the late stage. Also, the results demonstrate that adenosinergic and dopaminergic signaling modulation and the antioxidant action can be promising pharmacological strategies against end-stage symptoms of HD. |
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Bonan, Carla Denisehttp://lattes.cnpq.br/8058052532279136http://lattes.cnpq.br/3816230343785348Wiprich, Melissa Talita2023-05-11T15:05:51Z2023-03-13https://tede2.pucrs.br/tede2/handle/tede/10754Huntington?s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder. It is characterized by a neurobehavioral triad consisting of motor dysfunction, neuropsychiatric disturbance and cognitive decline. In HD the striatal neurons are degenerated leading to a decrease in dopamine D2 (D2R) and D1 (D1R), and adenosine A2A (A2AR) and A1 (A1R) leading to impaired movements such as chorea, bradykinesia, rigidity and locomotor incoordination. Furthermore, other molecular and biochemical mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation, neurodegeneration and changes in different neurotransmitter systems are involved in the pathophysiology of the disease. The 3-nitropropionic acid (3-NPA), a toxin derived from fungi and plants, can reproduce the behavioral phenotypes and biochemical alterations of HD. In the current study, we investigated the behavioral and morphological mechanisms in the brain and musculoskeletal system in adult zebrafish with 3-NPA-induced HD phenotype. For the biochemical and morphological analyses, adult zebrafish received a total of 7 intraperitoneal (i.p) injections (one injection every 4 days) of 3-NPA (60 mg/kg) for 28 days. On the 29th day, the brains were collected for histological, biochemical and molecular analyses. For the pharmacological modulation, on the 29th day after starting treatment, the animals receive a single i.p. injection of the following compounds: antioxidants, such as vitamin C (100 mg/kg); creatine (50 mg/kg) and melatonin (10 mg/kg); dopaminergic drugs, such as quinpirole (selective D2R agonist, 5 mg/kg) and eticlopride (selective D2R antagonist, 0.1 mg/kg); adenosinergic drugs such as CPA (selective A1R agonist, 1 mg/kg), CGS 21680 (selective A2AR agonist, 1 mg/kg), caffeine (non-selective antagonist of A1R e A2AR, 10 mg/kg), ZM 241385 (selective A2AR antagonist, 10 ?g/kg), DPCPX (selective A1R antagonist, 0.5 mg/kg), dipyridamole (nucleoside transporter inhibitor, 10 mg/kg), EHNA (adenosine deaminase inhibitor, 100 ?g/kg). After 30 min of i.p. injection, the locomotor activity and memory of the animals were evaluated. The histological results demonstrated that 3-NPA caused neurodegeneration and a decrease in granular cell in the brain tissue, but did not cause histological change in the cardiac and muscular tissue. Also, the results showed that there was not alteration in the TBARS and NPSH levels in the brain of adult zebrafish following 3-NPA treatment. Moreover, we observed that antioxidants vitamin C and creatine reversed the hypolocomotor effect induced by 3-NPA, while the memory deficit caused by 3-NPA was reversed by vitamin C and melatonin. Regarding the dopaminergic modulation, the 3-NPA caused decrease in dopamine, glutamate, and serotonin levels, but not did alter the gene expression of dopamine receptors. Also, the hypolocomotor effect and memory deficit induced by 3-NPA were reversed with quinpirole, but not with eticlopride. Caffeine and ZM 241385 reversed the hypolocomotor effect and memory deficit induced by 3-NPA, while the CGS 21680 potentiated the hypolocomotion and did not reverse the memory deficit induced by 3-NPA. In addition, CPA, DPCPX, dipyridamole and EHNA reversed the memory deficit induced by 3-NPA. Taken together, these data indicate that the 3-NPA treatment induces to behavioral phenotypes, histological and biochemical alterations as those observed in HD patients in the late stage. Also, the results demonstrate that adenosinergic and dopaminergic signaling modulation and the antioxidant action can be promising pharmacological strategies against end-stage symptoms of HD.A Doen?a de Huntington (DH) ? uma desordem neurodegenerativa, devastadora, progressiva e fatal. ? caracterizada por uma tr?ade comportamental que consiste em disfun??o motora, dist?rbios neuropsiqui?tricos e decl?nio cognitivo. Na DH, os neur?nios estriatais s?o degenerados, levando a uma diminui??o dos receptores de dopamina D2 (D2R) e D1 (D1R), e de adenosina A2A (A2AR) e A1 (A1R) levando a movimentos prejudicados como coreia, bradicinesia, rigidez e incoordena??o locomotora. Al?m disso, outros mecanismos moleculares e bioqu?micos, tais como disfun??o mitocondrial, estresse oxidativo, neuroinflama??o, neurodegenera??o e altera??o em diferentes sistemas de neurotransmiss?o est?o envolvidos na fisiopatologia da doen?a. O ?cido-3-nitropropi?nico (3-NPA), uma toxina derivada de plantas e fungos, pode reproduzir os fen?tipos comportamentais e altera??es bioqu?micas da DH. No presente estudo, investigamos os mecanismos comportamentais; bioquim?cos e moleculares no enc?falo, e morfol?gico no enc?falo sistema muscular e card?aco de peixe-zebra adultos com fen?tipo de DH induzido pelo 3-NPA. Para as an?lises bioqu?micas, moleculares e morfol?gicas, peixes-zebra adultos receberam um total de 7 inje??es intraperitoniais (i.p) (uma inje??o a cada 4 dias) de 3-NPA (60 mg/kg) por 28 dias. No 29? dia, os enc?falos foram coletados para a realiza??o das an?lises histol?gicas, bioqu?micas e moleculares. J? para a modula??o farmacol?gica, no 29? dia ap?s o in?cio do tratamento, os animais receberam uma ?nica inje??o i.p dos seguintes compostos: antioxidantes, como a vitamina C (100 mg/kg), creatina (50 mg/kg) e melatonina (10 mg/kg); f?rmacos dopamin?rgicos, como quinpirole (agonista seletivo de D2R, 5 mg/kg) e eticloprida (antagonista seletivo de D2R, 0.1 mg/kg); e f?rmacos adenosin?rgicos, como CPA (agonista seletivo de A1R, 1 mg/kg), CGS 21680 (agonista seletivo de A2AR, 1 mg/kg), cafe?na (antagonista n?o seletivo de A1R e A2AR, 10 mg/kg), ZM 241385 (antagonista seletivo de A2AR, 10 ?g/kg), DPCPX (antagonista seletivo de A1R, 0.5 mg/kg), dipiridamol (inibidor do transporte de nucleos?deos, 10 mg/kg), e EHNA (inibidor de adenosina desaminase, 100 ?g/kg). Ap?s 30 minutos da inje??o i.p., os animais tiveram a atividade locomotora e mem?ria avaliadas. Os resultados histol?gicos demonstraram que o 3-NPA causou neurodegenera??o e diminui??o das c?lulas granulares no tecido encef?lico, mas n?o causou mudan?a histol?gica no tecido card?aco e muscular. Tamb?m os resultados mostraram que n?o houve altera??o nos n?veis de TBARS e NPSH no enc?falo de peixes-zebra adultos ap?s o tratamento com o 3-NPA. Al?m disso, observamos que os antioxidantes vitamina C e creatina reverteram o efeito hipolocomotor induzido pelo 3-NPA, enquanto o d?ficit de mem?ria causado pelo 3-NPA foi revertido pela vitamina C e melatonina. Em rela??o a modula??o dopamin?rgica, o 3-NPA causou diminui??o nos n?veis de dopamina, glutamato e serotonina, por?m n?o alterou a express?o g?nica dos receptores de dopamina. Ademais, o efeito hipolocomotor e d?ficit de mem?ria induzido pelo 3-NPA foram revertidos com o quinpirole, mas n?o com a eticloprida. A cafe?na e o ZM 241385 reverteram o efeito hipolocomotor e d?ficit de mem?ria induzida pelo 3-NPA, enquanto CGS 21680 potencializou a altera??o motora e n?o reverteu o d?ficit de mem?ria causados pelo 3-NPA. Al?m disso, CPA, DPCPX, dipiridamol e EHNA reverteram o d?ficit cognitivo induzido pelo 3-NPA. Em conjunto, esses dados indicam que o tratamento com o 3-NPA induz a altera??es de fen?tipos comportamentais, histol?gicos e bioqu?micos semelhantes como as observadas em pacientes com DH no est?gio final. Al?m disso, os resultados demonstram que a modula??o da sinaliza??o adenosin?rgica, dopamin?rgica e a a??o antioxidante podem ser estrat?gias farmacol?gicas promissoras contra os sintomas do est?gio final da DH.Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2023-04-28T12:10:18Z No. of bitstreams: 1 Tesedoutorado_MelissaTalitaWiprich_vers?o oficial.pdf: 13027184 bytes, checksum: 376bb4cb17338b9cede4a6303933044d (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2023-05-11T14:51:58Z (GMT) No. of bitstreams: 1 Tesedoutorado_MelissaTalitaWiprich_vers?o oficial.pdf: 13027184 bytes, checksum: 376bb4cb17338b9cede4a6303933044d (MD5)Made available in DSpace on 2023-05-11T15:05:51Z (GMT). No. of bitstreams: 1 Tesedoutorado_MelissaTalitaWiprich_vers?o oficial.pdf: 13027184 bytes, checksum: 376bb4cb17338b9cede4a6303933044d (MD5) Previous issue date: 2023-03-13Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPqapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/187409/TES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Medicina e Ci?ncias da Sa?dePUCRSBrasilEscola de Medicina?cido-3-Nitropropi?nicoDoen?a de HuntingtonPeixe-ZebraReceptores de AdenosinaSistema Dopamin?rgicoHuntington?s Disease3-Nitropropionic AcidAdenosine ReceptorsDopaminergic SystemZebrafishCIENCIAS DA SAUDE::MEDICINAAvalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebrainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho ser? publicado como artigo ou livro60 meses11/05/2028-721401722658532398500500500600-224747486637135387-9693694523087866271802873727776104890info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.jpgTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.jpgimage/jpeg4101https://tede2.pucrs.br/tede2/bitstream/tede/10754/4/TES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.jpg7466d07290f70248eebfb130c15b3273MD54TEXTTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.txtTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.txttext/plain2069https://tede2.pucrs.br/tede2/bitstream/tede/10754/3/TES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf.txt3efb65b03bd0e169282a170d37bb5f8cMD53ORIGINALTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdfTES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdfapplication/pdf336578https://tede2.pucrs.br/tede2/bitstream/tede/10754/2/TES_MELISSA_TALITA_WIPRICH_CONFIDENCIAL.pdf7ef501b54b3c32338c3647d30e4a24c9MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590https://tede2.pucrs.br/tede2/bitstream/tede/10754/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/107542023-05-11 20:00:19.466oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2023-05-11T23:00:19Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
title |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
spellingShingle |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra Wiprich, Melissa Talita ?cido-3-Nitropropi?nico Doen?a de Huntington Peixe-Zebra Receptores de Adenosina Sistema Dopamin?rgico Huntington?s Disease 3-Nitropropionic Acid Adenosine Receptors Dopaminergic System Zebrafish CIENCIAS DA SAUDE::MEDICINA |
title_short |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
title_full |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
title_fullStr |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
title_full_unstemmed |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
title_sort |
Avalia??o de par?metros comportamentais, bioqu?micos e morfol?gicos no sistema nervoso central e m?sculoesquel?tico em um modelo de doen?a de huntington induzido pelo ?cido-3-nitropropi?nico em peixe-zebra |
author |
Wiprich, Melissa Talita |
author_facet |
Wiprich, Melissa Talita |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonan, Carla Denise |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8058052532279136 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3816230343785348 |
dc.contributor.author.fl_str_mv |
Wiprich, Melissa Talita |
contributor_str_mv |
Bonan, Carla Denise |
dc.subject.por.fl_str_mv |
?cido-3-Nitropropi?nico Doen?a de Huntington Peixe-Zebra Receptores de Adenosina Sistema Dopamin?rgico |
topic |
?cido-3-Nitropropi?nico Doen?a de Huntington Peixe-Zebra Receptores de Adenosina Sistema Dopamin?rgico Huntington?s Disease 3-Nitropropionic Acid Adenosine Receptors Dopaminergic System Zebrafish CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Huntington?s Disease 3-Nitropropionic Acid Adenosine Receptors Dopaminergic System Zebrafish |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
Huntington?s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder. It is characterized by a neurobehavioral triad consisting of motor dysfunction, neuropsychiatric disturbance and cognitive decline. In HD the striatal neurons are degenerated leading to a decrease in dopamine D2 (D2R) and D1 (D1R), and adenosine A2A (A2AR) and A1 (A1R) leading to impaired movements such as chorea, bradykinesia, rigidity and locomotor incoordination. Furthermore, other molecular and biochemical mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation, neurodegeneration and changes in different neurotransmitter systems are involved in the pathophysiology of the disease. The 3-nitropropionic acid (3-NPA), a toxin derived from fungi and plants, can reproduce the behavioral phenotypes and biochemical alterations of HD. In the current study, we investigated the behavioral and morphological mechanisms in the brain and musculoskeletal system in adult zebrafish with 3-NPA-induced HD phenotype. For the biochemical and morphological analyses, adult zebrafish received a total of 7 intraperitoneal (i.p) injections (one injection every 4 days) of 3-NPA (60 mg/kg) for 28 days. On the 29th day, the brains were collected for histological, biochemical and molecular analyses. For the pharmacological modulation, on the 29th day after starting treatment, the animals receive a single i.p. injection of the following compounds: antioxidants, such as vitamin C (100 mg/kg); creatine (50 mg/kg) and melatonin (10 mg/kg); dopaminergic drugs, such as quinpirole (selective D2R agonist, 5 mg/kg) and eticlopride (selective D2R antagonist, 0.1 mg/kg); adenosinergic drugs such as CPA (selective A1R agonist, 1 mg/kg), CGS 21680 (selective A2AR agonist, 1 mg/kg), caffeine (non-selective antagonist of A1R e A2AR, 10 mg/kg), ZM 241385 (selective A2AR antagonist, 10 ?g/kg), DPCPX (selective A1R antagonist, 0.5 mg/kg), dipyridamole (nucleoside transporter inhibitor, 10 mg/kg), EHNA (adenosine deaminase inhibitor, 100 ?g/kg). After 30 min of i.p. injection, the locomotor activity and memory of the animals were evaluated. The histological results demonstrated that 3-NPA caused neurodegeneration and a decrease in granular cell in the brain tissue, but did not cause histological change in the cardiac and muscular tissue. Also, the results showed that there was not alteration in the TBARS and NPSH levels in the brain of adult zebrafish following 3-NPA treatment. Moreover, we observed that antioxidants vitamin C and creatine reversed the hypolocomotor effect induced by 3-NPA, while the memory deficit caused by 3-NPA was reversed by vitamin C and melatonin. Regarding the dopaminergic modulation, the 3-NPA caused decrease in dopamine, glutamate, and serotonin levels, but not did alter the gene expression of dopamine receptors. Also, the hypolocomotor effect and memory deficit induced by 3-NPA were reversed with quinpirole, but not with eticlopride. Caffeine and ZM 241385 reversed the hypolocomotor effect and memory deficit induced by 3-NPA, while the CGS 21680 potentiated the hypolocomotion and did not reverse the memory deficit induced by 3-NPA. In addition, CPA, DPCPX, dipyridamole and EHNA reversed the memory deficit induced by 3-NPA. Taken together, these data indicate that the 3-NPA treatment induces to behavioral phenotypes, histological and biochemical alterations as those observed in HD patients in the late stage. Also, the results demonstrate that adenosinergic and dopaminergic signaling modulation and the antioxidant action can be promising pharmacological strategies against end-stage symptoms of HD. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-05-11T15:05:51Z |
dc.date.issued.fl_str_mv |
2023-03-13 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://tede2.pucrs.br/tede2/handle/tede/10754 |
url |
https://tede2.pucrs.br/tede2/handle/tede/10754 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
-721401722658532398 |
dc.relation.confidence.fl_str_mv |
500 500 500 600 |
dc.relation.department.fl_str_mv |
-224747486637135387 |
dc.relation.cnpq.fl_str_mv |
-969369452308786627 |
dc.relation.sponsorship.fl_str_mv |
1802873727776104890 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
dc.publisher.program.fl_str_mv |
Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de |
dc.publisher.initials.fl_str_mv |
PUCRS |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Escola de Medicina |
publisher.none.fl_str_mv |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) instacron:PUC_RS |
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Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
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