Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2005 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4436 |
Resumo: | Glutamatergic receptors are targets for many L-glutamate structure analogues, which cause neurotoxicity. This study investigated the actions of two dicarboxylic compounds, the first had cyclic framework and rigid structure, and the other had an acyclic framework and flexible structure, on the glutamatergic neurotransmission, oxidative damage and behavior in mice. The first compound evaluated was D,L-cis-2,3-pyrrolidine dicarboxylate (D,L-cis-2,3-PDC), a new glutamate analogue. D,L-cis-2,3-PDC reduced sodium-independent [3H]-L-glutamate binding by 50% in lysed membrane preparations and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration (ICV) of D,L-cis-2,3-PDC (7.5 - 25 nmol/ 5μl) induced dose-dependent tonic-clonic convulsions. The co-administration of MK-801 (7 nmol/ 2.5 μl; ICV), a noncompetitive NMDA receptor antagonist, with D,L-cis-2,3-PDC (16.5 nmol/ 2.5 μl; ICV) fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the co-administration of DNQX (10 nmol/ 2.5 μl; ICV), a AMPA and KA receptors antagonist, increased the latency to convulsion and did not alter the percentage of animals that had convulsions. These results suggest that D,L-cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors activation. The second compound studied was succinate, the accumulating substrate in succinate dehydrogenase (SDH) deficiencies and SDH inhibitor intoxication. Adult male mice received an ICV injection of succinate (0.7, 1.0 and 1.7 μmol/ 5 μl) or 0.9% NaCl (5 μl) and had their exploratory behavior assessed in an open field for 10 min. Succinate (0.7 and 1.0 μmol/ 5 μl) decreased locomotor activity behavior and increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation in the forebrain. Conversely, 1.7 μmol of succinate did not alter locomotor activity or oxidative damage parameters. The involvement of NMDA receptors in the succinate-induced increase of total protein carbonylation content and exploratory behavior inhibition was assessed by co-administrating MK-801 (7 nmol/ 2.5 μl, ICV) with succinate (1 μmol/ 2.5 μl, ICV). The co-administration of MK-801 protected against succinate-induced increase of total protein carbonylation and decrease of locomotor activity. These results suggest the involvement of NMDA receptors in these effects of succinate, which may of particular relevance for succinate-accumulating conditions, such as SDH inhibitors intoxication and inherited SDH deficiencies. |
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2017-05-022017-05-022005-07-27SINHORIN, Valeria Dornelles Gindri. 1,2 and 1,4-dicarboxylic compounds actuate on the glutamatergic system and the behavior of rats and mice. 2005. 85 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2005.http://repositorio.ufsm.br/handle/1/4436Glutamatergic receptors are targets for many L-glutamate structure analogues, which cause neurotoxicity. This study investigated the actions of two dicarboxylic compounds, the first had cyclic framework and rigid structure, and the other had an acyclic framework and flexible structure, on the glutamatergic neurotransmission, oxidative damage and behavior in mice. The first compound evaluated was D,L-cis-2,3-pyrrolidine dicarboxylate (D,L-cis-2,3-PDC), a new glutamate analogue. D,L-cis-2,3-PDC reduced sodium-independent [3H]-L-glutamate binding by 50% in lysed membrane preparations and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration (ICV) of D,L-cis-2,3-PDC (7.5 - 25 nmol/ 5μl) induced dose-dependent tonic-clonic convulsions. The co-administration of MK-801 (7 nmol/ 2.5 μl; ICV), a noncompetitive NMDA receptor antagonist, with D,L-cis-2,3-PDC (16.5 nmol/ 2.5 μl; ICV) fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the co-administration of DNQX (10 nmol/ 2.5 μl; ICV), a AMPA and KA receptors antagonist, increased the latency to convulsion and did not alter the percentage of animals that had convulsions. These results suggest that D,L-cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors activation. The second compound studied was succinate, the accumulating substrate in succinate dehydrogenase (SDH) deficiencies and SDH inhibitor intoxication. Adult male mice received an ICV injection of succinate (0.7, 1.0 and 1.7 μmol/ 5 μl) or 0.9% NaCl (5 μl) and had their exploratory behavior assessed in an open field for 10 min. Succinate (0.7 and 1.0 μmol/ 5 μl) decreased locomotor activity behavior and increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation in the forebrain. Conversely, 1.7 μmol of succinate did not alter locomotor activity or oxidative damage parameters. The involvement of NMDA receptors in the succinate-induced increase of total protein carbonylation content and exploratory behavior inhibition was assessed by co-administrating MK-801 (7 nmol/ 2.5 μl, ICV) with succinate (1 μmol/ 2.5 μl, ICV). The co-administration of MK-801 protected against succinate-induced increase of total protein carbonylation and decrease of locomotor activity. These results suggest the involvement of NMDA receptors in these effects of succinate, which may of particular relevance for succinate-accumulating conditions, such as SDH inhibitors intoxication and inherited SDH deficiencies.Os receptores glutamatérgicos são alvos da ação de muitas neurotoxinas análogas ao L-glutamato. Neste estudo foram investigadas as ações de dois compostos dicarboxílicos, um de cadeia cíclica e estrutura rígida e o outro de cadeia acíclica e estrutura flexível, sobre a neurotransmissão glutamatérgica, dano oxidativo e comportamento em roedores. No primeiro trabalho foi investigado se o D,L-cis-2,3-dicarboxilato de pirrolidina (D,L-cis-2,3-PDC) altera a ligação de [3H]-L-glutamato em membranas plasmáticas de córtex de ratos adultos e se os receptores N-metil-D-aspartato (NMDA) estão envolvidos nas convulsões induzidas por este composto. O D,L-cis-2,3-PDC reduziu a ligação de [3H]-L-glutamato Na+-independente em 50% nas preparações de membranas rompidas e não apresentou efeito sobre a ligação de [3H]-L-glutamato Na+-dependente. A administração intracerebroventricular (ICV) de D,L-cis-2,3-PDC (7,5; 25 nmol/ 5 μl) induziu convulsões generalizadas do tipo tônico-clônica nos camundongos, de uma maneira dose-dependente. A co-administração de MK-801 (7 nmol/ 2,5 μl; ICV), um antagonista não-competitivo dos receptores NMDA, com D,L-cis-2,3-PDC (16,5 nmol/ 2,5 μl; ICV), protegeu totalmente os animais das convulsões induzidas por D,L-cis-2,3-PDC, enquanto que a co-administração de DNQX (10 nmol/ 2,5 μl; ICV), um antagonista dos receptores AMPA e KA, aumentou a latência das convulsões, mas não alterou a percentagem de animais que tiveram convulsões. Estes resultados sugerem que os efeitos induzidos por D,L-cis-2,3-PDC são mediados principalmente pela ativação dos receptores NMDA. No segundo estudo, foi investigado se o sucinato, substrato que se acumula nas deficiências da enzima sucinato desidrogenase (SDH) e nas intoxicações por inibidores da SDH, causa lipoperoxidação e carbonilação protéica, e se os receptores NMDA estão envolvidos no dano oxidativo induzido por sucinato. Camundongos machos adultos receberam uma injeção ICV de sucinato (0,7; 1,0; 1,7 μmol/ 5 μl) ou 0,9 % de NaCl (5 μl) e seu comportamento foi analisado em um campo aberto por 10 minutos. Sucinato (0,7; 1,0 μmol/ 5 μl) diminuiu a atividade locomotora e aumentou as substâncias que reagem ao ácido tiobarbitúrico (TBARS) e carbonilação protéica no cérebro. Por outro lado, 1,7 μmol de sucinato não alterou a atividade locomotora ou os parâmetros de dano oxidativo. O envolvimento dos receptores NMDA no aumento induzido por sucinato do conteúdo de carbonilação protéica e da inibição do comportamento exploratório foi avaliado pela co-administração de MK-801 (7nmol/ 2,5 μl, ICV) com sucinato (1 μmol/ 2,5 μl, ICV). A co-administração de MK801 protegeu contra o aumento induzido por sucinato da carbonilação protéica e na diminuição da atividade locomotora. Esses resultados sugerem o envolvimento dos receptores NMDA nesses efeitos do sucinato, os quais são de grande relevância nas condições em que acumula sucinato, tais como as intoxicações com inibidores da SDH e deficiências dessa enzima causadas por erros inatos do metabolismo.application/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaMK-801ConvulsãoGlutamatoDNQXReceptores NMDAEspécies ativas de oxigênioMK-801ConvulsionGlutamateDNQXNMDA receptorsOxygen reactive speciesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICACompostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos1,2 and 1,4-dicarboxylic compounds actuate on the glutamatergic system and the behavior of rats and miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisMello, Carlos Fernando dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2Bonacorso, Helio Gauzehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0Weiblen, Rudihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783394D5Wannmacher, Clovis Milton Duvalhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783848Y0http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764518E7Sinhorin, Valeria Dornelles Gindri20080000000240050030050050030082e537b0-4a43-400e-9f82-0cd91952adeaf5f7d547-34eb-4614-9ee0-e0c46f51a69edbcce58b-96b0-4f45-a78d-ca6f339e038d37ea9445-0e57-453a-8f64-0498986410d8aa0a7432-03d4-4bab-b1c9-09db95737a7binfo:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTese VDGS 1-45.pdfapplication/pdf1342598http://repositorio.ufsm.br/bitstream/1/4436/1/Tese%20VDGS%201-45.pdf748ef49f21f4da4687c4cb2c2eadff3fMD51Teses VDGS 46-54.pdfTeses VDGS 46-54.pdfapplication/pdf1851499http://repositorio.ufsm.br/bitstream/1/4436/4/Teses%20VDGS%2046-54.pdf1e28055a9923865025835d9fe3b079b9MD54Teses VDGS 55-85.pdfTeses VDGS 55-85.pdfapplication/pdf1781328http://repositorio.ufsm.br/bitstream/1/4436/5/Teses%20VDGS%2055-85.pdfe1feec8e9d284bf0e336633434a6d453MD55TEXTTese VDGS 1-45.pdf.txtTese VDGS 1-45.pdf.txtExtracted texttext/plain70906http://repositorio.ufsm.br/bitstream/1/4436/2/Tese%20VDGS%201-45.pdf.txt0d1d171d90d4db0a40a77addb3e87272MD52Teses VDGS 46-54.pdf.txtTeses VDGS 46-54.pdf.txtExtracted texttext/plain1204http://repositorio.ufsm.br/bitstream/1/4436/6/Teses%20VDGS%2046-54.pdf.txt57625bc868b4dae876c9e11159c96678MD56Teses VDGS 55-85.pdf.txtTeses VDGS 55-85.pdf.txtExtracted texttext/plain59512http://repositorio.ufsm.br/bitstream/1/4436/8/Teses%20VDGS%2055-85.pdf.txt082d4a1363dfeb2ede51d40a20b3ed9eMD58THUMBNAILTese VDGS 1-45.pdf.jpgTese VDGS 1-45.pdf.jpgIM Thumbnailimage/jpeg5449http://repositorio.ufsm.br/bitstream/1/4436/3/Tese%20VDGS%201-45.pdf.jpga4113aaa04e4e6cdd72415069b23760bMD53Teses VDGS 46-54.pdf.jpgTeses VDGS 46-54.pdf.jpgIM Thumbnailimage/jpeg4483http://repositorio.ufsm.br/bitstream/1/4436/7/Teses%20VDGS%2046-54.pdf.jpgf6f00f6692aeeb2b48592fdfb1d168afMD57Teses VDGS 55-85.pdf.jpgTeses VDGS 55-85.pdf.jpgIM Thumbnailimage/jpeg7692http://repositorio.ufsm.br/bitstream/1/4436/9/Teses%20VDGS%2055-85.pdf.jpgd9fd29aa7faa4be54a2d9d47e9173a44MD591/44362017-07-25 11:06:33.341oai:repositorio.ufsm.br:1/4436Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132017-07-25T14:06:33Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
dc.title.alternative.eng.fl_str_mv |
1,2 and 1,4-dicarboxylic compounds actuate on the glutamatergic system and the behavior of rats and mice |
title |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
spellingShingle |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos Sinhorin, Valeria Dornelles Gindri MK-801 Convulsão Glutamato DNQX Receptores NMDA Espécies ativas de oxigênio MK-801 Convulsion Glutamate DNQX NMDA receptors Oxygen reactive species CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
title_full |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
title_fullStr |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
title_full_unstemmed |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
title_sort |
Compostos 1,2 e 1,4-dicarboxílicos atuam sobre o sistema glutamatérgico e o comportamento de ratos e camundongos |
author |
Sinhorin, Valeria Dornelles Gindri |
author_facet |
Sinhorin, Valeria Dornelles Gindri |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Mello, Carlos Fernando de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2 |
dc.contributor.referee1.fl_str_mv |
Bonacorso, Helio Gauze |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0 |
dc.contributor.referee2.fl_str_mv |
Weiblen, Rudi |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783394D5 |
dc.contributor.referee3.fl_str_mv |
Wannmacher, Clovis Milton Duval |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783848Y0 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764518E7 |
dc.contributor.author.fl_str_mv |
Sinhorin, Valeria Dornelles Gindri |
contributor_str_mv |
Mello, Carlos Fernando de Bonacorso, Helio Gauze Weiblen, Rudi Wannmacher, Clovis Milton Duval |
dc.subject.por.fl_str_mv |
MK-801 Convulsão Glutamato DNQX Receptores NMDA Espécies ativas de oxigênio |
topic |
MK-801 Convulsão Glutamato DNQX Receptores NMDA Espécies ativas de oxigênio MK-801 Convulsion Glutamate DNQX NMDA receptors Oxygen reactive species CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
MK-801 Convulsion Glutamate DNQX NMDA receptors Oxygen reactive species |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Glutamatergic receptors are targets for many L-glutamate structure analogues, which cause neurotoxicity. This study investigated the actions of two dicarboxylic compounds, the first had cyclic framework and rigid structure, and the other had an acyclic framework and flexible structure, on the glutamatergic neurotransmission, oxidative damage and behavior in mice. The first compound evaluated was D,L-cis-2,3-pyrrolidine dicarboxylate (D,L-cis-2,3-PDC), a new glutamate analogue. D,L-cis-2,3-PDC reduced sodium-independent [3H]-L-glutamate binding by 50% in lysed membrane preparations and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration (ICV) of D,L-cis-2,3-PDC (7.5 - 25 nmol/ 5μl) induced dose-dependent tonic-clonic convulsions. The co-administration of MK-801 (7 nmol/ 2.5 μl; ICV), a noncompetitive NMDA receptor antagonist, with D,L-cis-2,3-PDC (16.5 nmol/ 2.5 μl; ICV) fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the co-administration of DNQX (10 nmol/ 2.5 μl; ICV), a AMPA and KA receptors antagonist, increased the latency to convulsion and did not alter the percentage of animals that had convulsions. These results suggest that D,L-cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors activation. The second compound studied was succinate, the accumulating substrate in succinate dehydrogenase (SDH) deficiencies and SDH inhibitor intoxication. Adult male mice received an ICV injection of succinate (0.7, 1.0 and 1.7 μmol/ 5 μl) or 0.9% NaCl (5 μl) and had their exploratory behavior assessed in an open field for 10 min. Succinate (0.7 and 1.0 μmol/ 5 μl) decreased locomotor activity behavior and increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation in the forebrain. Conversely, 1.7 μmol of succinate did not alter locomotor activity or oxidative damage parameters. The involvement of NMDA receptors in the succinate-induced increase of total protein carbonylation content and exploratory behavior inhibition was assessed by co-administrating MK-801 (7 nmol/ 2.5 μl, ICV) with succinate (1 μmol/ 2.5 μl, ICV). The co-administration of MK-801 protected against succinate-induced increase of total protein carbonylation and decrease of locomotor activity. These results suggest the involvement of NMDA receptors in these effects of succinate, which may of particular relevance for succinate-accumulating conditions, such as SDH inhibitors intoxication and inherited SDH deficiencies. |
publishDate |
2005 |
dc.date.issued.fl_str_mv |
2005-07-27 |
dc.date.accessioned.fl_str_mv |
2017-05-02 |
dc.date.available.fl_str_mv |
2017-05-02 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
SINHORIN, Valeria Dornelles Gindri. 1,2 and 1,4-dicarboxylic compounds actuate on the glutamatergic system and the behavior of rats and mice. 2005. 85 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2005. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4436 |
identifier_str_mv |
SINHORIN, Valeria Dornelles Gindri. 1,2 and 1,4-dicarboxylic compounds actuate on the glutamatergic system and the behavior of rats and mice. 2005. 85 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2005. |
url |
http://repositorio.ufsm.br/handle/1/4436 |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
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UFSM |
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BR |
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Bioquímica |
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Universidade Federal de Santa Maria |
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