Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFC |
Texto Completo: | http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=414 |
Resumo: | Temproromandibular disfunction (TMD) is related to a masticatory system disfunction which can include the temporomandibular joint (TMJ), the masticatory muscles and/or other related structures. TMJ inflammatory disorders are one of the major pathology of TMD afecting a great number of patients. Although TMJÂs inflammation and pain are important cinical entities, their mechanisms are poorly understood. The purpose of the study is to propose an experimetnal model of TMJÂs arthritis to study its patophysiological mechanisms and inflammatory mediators such as nitric oxide (NO). Female Wistar rats (160-220 g) were used to the study. To induct TMJÂs arthritis, zymosan 40 microL (Zy: 0,25; 0,5; 1 ou 2 mg) was injected into left TMJ. The animals were sacrified in times 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 days. Nitric oxide syntase inhibitors L-NAME (10, 30 e 100 mg/kg i.p.) or 1400W (0,5 e 1 mg/kg s.c.) were administered 30 min before TMJÂs arthritis induction. Leucocyte influx count in the sinovial fluid, vascular permability study using Evans blue dye extravasation, myeloperoxidase assay (MPO), NO production determination using Griess reaction, histopatological analyisis and imunohystochemical for induced NO synthase (iNOS) were utilized as parameters of this sutudy. It was observed that Zy (2 mg) induced significantly increase in leucocyte influx count (p<0,05), Evans blue dyeÂs extravasation (p<0,05), myeloperoxidase activity (p<0,05) and NO dosage (p<0,05) compared with control group 6 h after TMJ arthritis induction. Histopatological analysis of TMJ of Zy injected animals showed inflammatory cell infiltration in synovial membrane (SM), in conective periarticular tissue, in squeletic muscle tissue and thickness of SM in 6 h after TMJ arthritis. On the 10th day after TMJ arthritis, the TMJ remain showing leucocyte infiltration to synovial membrane (SM), to conective periarticular tissue, to squeletic muscle tissue and thickness of SM, as well as fibrosis of SM and articular disc. On the 21st d after TMJ arthritis, it was observed cell influx only to SM, showing, however, thickness of SM and the major fibrosis of SM, articular cartilage, conective periarticular tissue and articular disc. TMJÂs imunohistochemistry reaction for iNOS showed increase iNOSÂs expression in animals with TMJÂs arthritis compared to the control group. L-NAME 100 mg/kg and 1400W 1 mg/kg reduced the increase in leucocyte count in the synovial fluid, the Evans blue dye extravasation, the histopatological alterations, and reduced the iNOS expression after imunohistochemistry reaction for iNOS 6 h after TMJ arthritis. These results sugest that this experimental model can be used to study TMJ arthritis, and that NO can participate in the physiopathological mechanisms of TMD. |
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info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisExperimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxidePadronizaÃÃo de modelo experimental de artrite na articulaÃÃo temporomandibular induzida por zymozan em ratos e estudo do papel do Ãxido nÃtrico2006-07-11Gerly Anne de Castro Brito24198846391http://lattes.cnpq.br/8991062042568398Francisco Airton Castro da Rocha23373474353http://lattes.cnpq.br/4916026652021507Henrique Clasen Sarparo86283065872http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4790508J784184930387http://lattes.cnpq.br/4727435604122670HellÃada Vasconcelos ChavesUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBRArticulaÃÃo temporomandibular Artrite experimental Ãxido nÃtrico Zymosan SÃndrome de disfunÃÃo da articulaÃÃo temporomandibularTemporomandibular joint Experimental arthritis Nitric oxide Zymosan Syndrome of temporomandibular joint dysfunctionFARMACOLOGIATemproromandibular disfunction (TMD) is related to a masticatory system disfunction which can include the temporomandibular joint (TMJ), the masticatory muscles and/or other related structures. TMJ inflammatory disorders are one of the major pathology of TMD afecting a great number of patients. Although TMJÂs inflammation and pain are important cinical entities, their mechanisms are poorly understood. The purpose of the study is to propose an experimetnal model of TMJÂs arthritis to study its patophysiological mechanisms and inflammatory mediators such as nitric oxide (NO). Female Wistar rats (160-220 g) were used to the study. To induct TMJÂs arthritis, zymosan 40 microL (Zy: 0,25; 0,5; 1 ou 2 mg) was injected into left TMJ. The animals were sacrified in times 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 days. Nitric oxide syntase inhibitors L-NAME (10, 30 e 100 mg/kg i.p.) or 1400W (0,5 e 1 mg/kg s.c.) were administered 30 min before TMJÂs arthritis induction. Leucocyte influx count in the sinovial fluid, vascular permability study using Evans blue dye extravasation, myeloperoxidase assay (MPO), NO production determination using Griess reaction, histopatological analyisis and imunohystochemical for induced NO synthase (iNOS) were utilized as parameters of this sutudy. It was observed that Zy (2 mg) induced significantly increase in leucocyte influx count (p<0,05), Evans blue dyeÂs extravasation (p<0,05), myeloperoxidase activity (p<0,05) and NO dosage (p<0,05) compared with control group 6 h after TMJ arthritis induction. Histopatological analysis of TMJ of Zy injected animals showed inflammatory cell infiltration in synovial membrane (SM), in conective periarticular tissue, in squeletic muscle tissue and thickness of SM in 6 h after TMJ arthritis. On the 10th day after TMJ arthritis, the TMJ remain showing leucocyte infiltration to synovial membrane (SM), to conective periarticular tissue, to squeletic muscle tissue and thickness of SM, as well as fibrosis of SM and articular disc. On the 21st d after TMJ arthritis, it was observed cell influx only to SM, showing, however, thickness of SM and the major fibrosis of SM, articular cartilage, conective periarticular tissue and articular disc. TMJÂs imunohistochemistry reaction for iNOS showed increase iNOSÂs expression in animals with TMJÂs arthritis compared to the control group. L-NAME 100 mg/kg and 1400W 1 mg/kg reduced the increase in leucocyte count in the synovial fluid, the Evans blue dye extravasation, the histopatological alterations, and reduced the iNOS expression after imunohistochemistry reaction for iNOS 6 h after TMJ arthritis. These results sugest that this experimental model can be used to study TMJ arthritis, and that NO can participate in the physiopathological mechanisms of TMD.DisfunÃÃo temporomandibular (DTM) à um distÃrbio relacionado à funÃÃo do sistema mastigatÃrio que acomete as articulaÃÃes temporomandibulares (ATM), os mÃsculos mastigatÃrios e/ou estruturas associadas. As desordens inflamatÃrias na ATM classificam-se como uma das quatro classes de DTM, estando presente em um grande nÃmero de pacientes. Embora a inflamaÃÃo e a dor nas estruturas articulares sejam entidades clÃnicas importantes, seus mecanismos sÃo pouco compreendidos. Objetivamos montar modelo experimental de artrite na ATM para estudar a fisiopatologia da doenÃa e a participaÃÃo de mediadores inflamatÃrios como Ãxido nÃtrico (NO). Foram utilizados ratos Wistar fÃmeas (160-220 g) nos quais se injetou 40 microlitros de zymosan (Zy: 0,25; 0,5; 1 ou 2 mg) na ATM esquerda dos animais para induÃÃo de artrite. Esses animais foram sacrificados nos tempos de 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 dias. Utilizaram-se inibidores da sÃntese de Ãxido nÃtrico L-NAME (10, 30 e 100 mg/kg i.p.) ou 1400W (0,5 e 1 mg/kg s.c.) os quais foram injetados 30 min antes da induÃÃo da artrite. ParÃmetros de contagem do influxo celular no lÃquido sinovial, estudo da permeabilidade vascular pelo extravasamento de azul de Evans, estudo do ensaio de mieloperoxidase (MPO), determinaÃÃo da produÃÃo de Ãxido nÃtrico atravÃs da dosagem de nitrito pelo mÃtodo de Griess, anÃlise histopatolÃgica e imunohistoquÃmica para NO sintase induzida (NOSi) foram avaliados. Observamos que Zy (2 mg) induziu aumento significativo do influxo celular no lÃquido sinovial (p<0,05), do extravasamento de azul de Evans (p<0,05), da atividade de mieloperoxidase (p<0,05) e da dosagem de nitrito/nitrato (p<0,05) na 6 h apÃs induÃÃo da artrite em relaÃÃo ao grupo controle. A anÃlise histopatolÃgica mostrou que Zy (2 mg) induziu, de forma significativa, infiltrado celular na membrana sinovial, no tecido conjuntivo periarticular, no tecido muscular esquelÃtico e espessamento da MS na 6 h apÃs induÃÃo da artrite. No 10 d apÃs induÃÃo da artrite, continua a apresentar infiltrado celular na MS, no tecido conjuntivo periarticular, no tecido muscular esquelÃtico e espessamento da MS, assim como passa a apresentar fibrose da MS e do disco articular. No 21 dia apÃs induÃÃo da artrite, foram observados infiltrado celular apenas na MS, com espessamento da mesma, e aumento da fibrose da membrana sinovial, da cartilagem articular, do tecido periarticular e do disco articular, significativamente diferentes em relaÃÃo ao grupo controle. à anÃlise da reaÃÃo de imunohistoquÃmica para NOSi, observou-se aumento da expressÃo de NOSi no animais com Zy (2 mg). Tanto L-NAME 100 mg/kg quanto 1400W 1 mg/kg (p<0,05) foram capazes de reverter o aumento do influxo celular no lÃquido sinovial da ATM (p<0,05), o extravasamento plasmÃtico (p<0,05), as alteraÃÃes histopatolÃgicas e a expressÃo de NOSi pelo estudo da reaÃÃo de imunohistoquÃmica para NOSi observadas na 6 h apÃs induÃÃo da artrite. Esses resultados sugerem que o modelo experimental proposto se presta ao estudo da artrite na ATM, e que NO participa na fisiopatologia do processo inflamatÃrio da DTM.Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicohttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=414application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:13:31Zmail@mail.com - |
dc.title.en.fl_str_mv |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
dc.title.alternative.pt.fl_str_mv |
PadronizaÃÃo de modelo experimental de artrite na articulaÃÃo temporomandibular induzida por zymozan em ratos e estudo do papel do Ãxido nÃtrico |
title |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
spellingShingle |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide HellÃada Vasconcelos Chaves ArticulaÃÃo temporomandibular Artrite experimental Ãxido nÃtrico Zymosan SÃndrome de disfunÃÃo da articulaÃÃo temporomandibular Temporomandibular joint Experimental arthritis Nitric oxide Zymosan Syndrome of temporomandibular joint dysfunction FARMACOLOGIA |
title_short |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
title_full |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
title_fullStr |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
title_full_unstemmed |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
title_sort |
Experimental model of temporomandibular joint arthritis induced by zymozan in rats and the study of the role of nitric oxide |
author |
HellÃada Vasconcelos Chaves |
author_facet |
HellÃada Vasconcelos Chaves |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gerly Anne de Castro Brito |
dc.contributor.advisor1ID.fl_str_mv |
24198846391 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8991062042568398 |
dc.contributor.referee1.fl_str_mv |
Francisco Airton Castro da Rocha |
dc.contributor.referee1ID.fl_str_mv |
23373474353 |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4916026652021507 |
dc.contributor.referee2.fl_str_mv |
Henrique Clasen Sarparo |
dc.contributor.referee2ID.fl_str_mv |
86283065872 |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4790508J7 |
dc.contributor.authorID.fl_str_mv |
84184930387 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4727435604122670 |
dc.contributor.author.fl_str_mv |
HellÃada Vasconcelos Chaves |
contributor_str_mv |
Gerly Anne de Castro Brito Francisco Airton Castro da Rocha Henrique Clasen Sarparo |
dc.subject.por.fl_str_mv |
ArticulaÃÃo temporomandibular Artrite experimental Ãxido nÃtrico Zymosan SÃndrome de disfunÃÃo da articulaÃÃo temporomandibular |
topic |
ArticulaÃÃo temporomandibular Artrite experimental Ãxido nÃtrico Zymosan SÃndrome de disfunÃÃo da articulaÃÃo temporomandibular Temporomandibular joint Experimental arthritis Nitric oxide Zymosan Syndrome of temporomandibular joint dysfunction FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Temporomandibular joint Experimental arthritis Nitric oxide Zymosan Syndrome of temporomandibular joint dysfunction |
dc.subject.cnpq.fl_str_mv |
FARMACOLOGIA |
dc.description.sponsorship.fl_txt_mv |
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico |
dc.description.abstract.por.fl_txt_mv |
Temproromandibular disfunction (TMD) is related to a masticatory system disfunction which can include the temporomandibular joint (TMJ), the masticatory muscles and/or other related structures. TMJ inflammatory disorders are one of the major pathology of TMD afecting a great number of patients. Although TMJÂs inflammation and pain are important cinical entities, their mechanisms are poorly understood. The purpose of the study is to propose an experimetnal model of TMJÂs arthritis to study its patophysiological mechanisms and inflammatory mediators such as nitric oxide (NO). Female Wistar rats (160-220 g) were used to the study. To induct TMJÂs arthritis, zymosan 40 microL (Zy: 0,25; 0,5; 1 ou 2 mg) was injected into left TMJ. The animals were sacrified in times 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 days. Nitric oxide syntase inhibitors L-NAME (10, 30 e 100 mg/kg i.p.) or 1400W (0,5 e 1 mg/kg s.c.) were administered 30 min before TMJÂs arthritis induction. Leucocyte influx count in the sinovial fluid, vascular permability study using Evans blue dye extravasation, myeloperoxidase assay (MPO), NO production determination using Griess reaction, histopatological analyisis and imunohystochemical for induced NO synthase (iNOS) were utilized as parameters of this sutudy. It was observed that Zy (2 mg) induced significantly increase in leucocyte influx count (p<0,05), Evans blue dyeÂs extravasation (p<0,05), myeloperoxidase activity (p<0,05) and NO dosage (p<0,05) compared with control group 6 h after TMJ arthritis induction. Histopatological analysis of TMJ of Zy injected animals showed inflammatory cell infiltration in synovial membrane (SM), in conective periarticular tissue, in squeletic muscle tissue and thickness of SM in 6 h after TMJ arthritis. On the 10th day after TMJ arthritis, the TMJ remain showing leucocyte infiltration to synovial membrane (SM), to conective periarticular tissue, to squeletic muscle tissue and thickness of SM, as well as fibrosis of SM and articular disc. On the 21st d after TMJ arthritis, it was observed cell influx only to SM, showing, however, thickness of SM and the major fibrosis of SM, articular cartilage, conective periarticular tissue and articular disc. TMJÂs imunohistochemistry reaction for iNOS showed increase iNOSÂs expression in animals with TMJÂs arthritis compared to the control group. L-NAME 100 mg/kg and 1400W 1 mg/kg reduced the increase in leucocyte count in the synovial fluid, the Evans blue dye extravasation, the histopatological alterations, and reduced the iNOS expression after imunohistochemistry reaction for iNOS 6 h after TMJ arthritis. These results sugest that this experimental model can be used to study TMJ arthritis, and that NO can participate in the physiopathological mechanisms of TMD. DisfunÃÃo temporomandibular (DTM) à um distÃrbio relacionado à funÃÃo do sistema mastigatÃrio que acomete as articulaÃÃes temporomandibulares (ATM), os mÃsculos mastigatÃrios e/ou estruturas associadas. As desordens inflamatÃrias na ATM classificam-se como uma das quatro classes de DTM, estando presente em um grande nÃmero de pacientes. Embora a inflamaÃÃo e a dor nas estruturas articulares sejam entidades clÃnicas importantes, seus mecanismos sÃo pouco compreendidos. Objetivamos montar modelo experimental de artrite na ATM para estudar a fisiopatologia da doenÃa e a participaÃÃo de mediadores inflamatÃrios como Ãxido nÃtrico (NO). Foram utilizados ratos Wistar fÃmeas (160-220 g) nos quais se injetou 40 microlitros de zymosan (Zy: 0,25; 0,5; 1 ou 2 mg) na ATM esquerda dos animais para induÃÃo de artrite. Esses animais foram sacrificados nos tempos de 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 dias. Utilizaram-se inibidores da sÃntese de Ãxido nÃtrico L-NAME (10, 30 e 100 mg/kg i.p.) ou 1400W (0,5 e 1 mg/kg s.c.) os quais foram injetados 30 min antes da induÃÃo da artrite. ParÃmetros de contagem do influxo celular no lÃquido sinovial, estudo da permeabilidade vascular pelo extravasamento de azul de Evans, estudo do ensaio de mieloperoxidase (MPO), determinaÃÃo da produÃÃo de Ãxido nÃtrico atravÃs da dosagem de nitrito pelo mÃtodo de Griess, anÃlise histopatolÃgica e imunohistoquÃmica para NO sintase induzida (NOSi) foram avaliados. Observamos que Zy (2 mg) induziu aumento significativo do influxo celular no lÃquido sinovial (p<0,05), do extravasamento de azul de Evans (p<0,05), da atividade de mieloperoxidase (p<0,05) e da dosagem de nitrito/nitrato (p<0,05) na 6 h apÃs induÃÃo da artrite em relaÃÃo ao grupo controle. A anÃlise histopatolÃgica mostrou que Zy (2 mg) induziu, de forma significativa, infiltrado celular na membrana sinovial, no tecido conjuntivo periarticular, no tecido muscular esquelÃtico e espessamento da MS na 6 h apÃs induÃÃo da artrite. No 10 d apÃs induÃÃo da artrite, continua a apresentar infiltrado celular na MS, no tecido conjuntivo periarticular, no tecido muscular esquelÃtico e espessamento da MS, assim como passa a apresentar fibrose da MS e do disco articular. No 21 dia apÃs induÃÃo da artrite, foram observados infiltrado celular apenas na MS, com espessamento da mesma, e aumento da fibrose da membrana sinovial, da cartilagem articular, do tecido periarticular e do disco articular, significativamente diferentes em relaÃÃo ao grupo controle. à anÃlise da reaÃÃo de imunohistoquÃmica para NOSi, observou-se aumento da expressÃo de NOSi no animais com Zy (2 mg). Tanto L-NAME 100 mg/kg quanto 1400W 1 mg/kg (p<0,05) foram capazes de reverter o aumento do influxo celular no lÃquido sinovial da ATM (p<0,05), o extravasamento plasmÃtico (p<0,05), as alteraÃÃes histopatolÃgicas e a expressÃo de NOSi pelo estudo da reaÃÃo de imunohistoquÃmica para NOSi observadas na 6 h apÃs induÃÃo da artrite. Esses resultados sugerem que o modelo experimental proposto se presta ao estudo da artrite na ATM, e que NO participa na fisiopatologia do processo inflamatÃrio da DTM. |
description |
Temproromandibular disfunction (TMD) is related to a masticatory system disfunction which can include the temporomandibular joint (TMJ), the masticatory muscles and/or other related structures. TMJ inflammatory disorders are one of the major pathology of TMD afecting a great number of patients. Although TMJÂs inflammation and pain are important cinical entities, their mechanisms are poorly understood. The purpose of the study is to propose an experimetnal model of TMJÂs arthritis to study its patophysiological mechanisms and inflammatory mediators such as nitric oxide (NO). Female Wistar rats (160-220 g) were used to the study. To induct TMJÂs arthritis, zymosan 40 microL (Zy: 0,25; 0,5; 1 ou 2 mg) was injected into left TMJ. The animals were sacrified in times 3 h, 6 h, 1, 2, 3, 5, 7, 10 e 21 days. Nitric oxide syntase inhibitors L-NAME (10, 30 e 100 mg/kg i.p.) or 1400W (0,5 e 1 mg/kg s.c.) were administered 30 min before TMJÂs arthritis induction. Leucocyte influx count in the sinovial fluid, vascular permability study using Evans blue dye extravasation, myeloperoxidase assay (MPO), NO production determination using Griess reaction, histopatological analyisis and imunohystochemical for induced NO synthase (iNOS) were utilized as parameters of this sutudy. It was observed that Zy (2 mg) induced significantly increase in leucocyte influx count (p<0,05), Evans blue dyeÂs extravasation (p<0,05), myeloperoxidase activity (p<0,05) and NO dosage (p<0,05) compared with control group 6 h after TMJ arthritis induction. Histopatological analysis of TMJ of Zy injected animals showed inflammatory cell infiltration in synovial membrane (SM), in conective periarticular tissue, in squeletic muscle tissue and thickness of SM in 6 h after TMJ arthritis. On the 10th day after TMJ arthritis, the TMJ remain showing leucocyte infiltration to synovial membrane (SM), to conective periarticular tissue, to squeletic muscle tissue and thickness of SM, as well as fibrosis of SM and articular disc. On the 21st d after TMJ arthritis, it was observed cell influx only to SM, showing, however, thickness of SM and the major fibrosis of SM, articular cartilage, conective periarticular tissue and articular disc. TMJÂs imunohistochemistry reaction for iNOS showed increase iNOSÂs expression in animals with TMJÂs arthritis compared to the control group. L-NAME 100 mg/kg and 1400W 1 mg/kg reduced the increase in leucocyte count in the synovial fluid, the Evans blue dye extravasation, the histopatological alterations, and reduced the iNOS expression after imunohistochemistry reaction for iNOS 6 h after TMJ arthritis. These results sugest that this experimental model can be used to study TMJ arthritis, and that NO can participate in the physiopathological mechanisms of TMD. |
publishDate |
2006 |
dc.date.issued.fl_str_mv |
2006-07-11 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
status_str |
publishedVersion |
format |
masterThesis |
dc.identifier.uri.fl_str_mv |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=414 |
url |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=414 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Cearà |
dc.publisher.program.fl_str_mv |
Programa de PÃs-GraduaÃÃo em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFC |
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BR |
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Universidade Federal do Cearà |
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reponame:Biblioteca Digital de Teses e Dissertações da UFC instname:Universidade Federal do Ceará instacron:UFC |
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Biblioteca Digital de Teses e Dissertações da UFC |
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Universidade Federal do Ceará |
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UFC |
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