Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis

Detalhes bibliográficos
Autor(a) principal: Peres, Priscila Rodrigues
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF)
Texto Completo: http://tede.upf.br:8080/jspui/handle/tede/1727
Resumo: The pork production chain is one of the most important sectors in Brazil and it is continuously in progress in order to get high development, updating and global recognition. The respiratory diseases of swine are considered a high animal health challenge for industrial pig farms since they can be highly transmissible within a production unit. Amongst the pathogens related to the swine respiratory complex, Haemophilus parasuis has emerged as one of the most important and it affects piglets mainly in the nursery phases producing important economic losses for the industry. Vaccination stands out as the main form of prevent Glässer’s disease (GD), but the current commercial vaccines do not guarantee protective cross-immunity due to the high phenotypic variability of the clinical strains of H. parasuis. Consequently, protection failures occur especially when the farm is infected with a serovar different from those contained in the vaccine. Thus, the use of antimicrobials to treat diseased animals is essential, as is the surveillance of the susceptibility profile of the antibiotics used for this purpose, due to the continuous appearance of resistant strains, which makes it difficult to predict the efficacy of any molecule without prior evaluation. Tildipirosin is a last generation macrolide that has been recently used in pigs in Brazil, and its chemical structure is aimed at hindering the emergence of bacterial resistance. Due to the importance of continuous evaluation of antibiotics against bacteria able to trigger diseases in pigs, here, we have evaluated the susceptibility profile of 100 clinical strains of H. parasuis to tildipirosin. All strains included in this study were isolated from pigs with Glässer's disease. From the total, 58 strains were isolated from systemic sites (joints, peritoneum, pericardium and brain) and 42 were recovered from lung tissue. Each strain represents an individual clinical case of GD. The tildipirosin susceptibility test was carried out using the broth microdilution technique, evaluating the minimum inhibitory concentration (MIC) of the product (0.03 - 256 μg / ml). Our results demonstrate that in general the clinical strains of H. parasuis are susceptible to tildipirosin, with MIC50 and MIC90 of 0.25 and 32 μg / ml, respectively. The tildipirosin susceptibility analysis relative to the sample isolation site showed that the strains from systemic sites presented a MIC50 (0.25 μg/ml) higher than those observed in strains of pulmonary origin (0.12 μg/ml). Taking into account the maximum tissue concentration of tildipirosin after parenteral administration of the therapeutic dose (4 mg / kg) of the commercial product Zuprevo® (MSD, Brazil), 72% of the strains could be potentially affected. A small dose adjustment taking into consideration the MICs values could increase the breadth of the efficacy of the product. However, it would not be sufficient to treat 8% of the strains, which have been shown to be highly resistant to the tildipirosin. In summary, our results indicate that tildipirosin may be recommended for the clinical treatment of pigs suffering Glässer's disease, however, because of the presence of strains already resistant to the antibiotic, the MIC test should be periodically used to (i) determine the therapeutic dos e and (ii) monitoring the H. parasuis susceptibility profile to tildipirosin.
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spelling Frandoloso, Rafael03912065918http://lattes.cnpq.br/250289135401741000821198050http://lattes.cnpq.br/8743231875258102Peres, Priscila Rodrigues2019-07-08T11:38:23Z2018-09-28PERES, Priscila Rodrigues Priscila Rodrigues. Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis. 2018. 64 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2018.http://tede.upf.br:8080/jspui/handle/tede/1727The pork production chain is one of the most important sectors in Brazil and it is continuously in progress in order to get high development, updating and global recognition. The respiratory diseases of swine are considered a high animal health challenge for industrial pig farms since they can be highly transmissible within a production unit. Amongst the pathogens related to the swine respiratory complex, Haemophilus parasuis has emerged as one of the most important and it affects piglets mainly in the nursery phases producing important economic losses for the industry. Vaccination stands out as the main form of prevent Glässer’s disease (GD), but the current commercial vaccines do not guarantee protective cross-immunity due to the high phenotypic variability of the clinical strains of H. parasuis. Consequently, protection failures occur especially when the farm is infected with a serovar different from those contained in the vaccine. Thus, the use of antimicrobials to treat diseased animals is essential, as is the surveillance of the susceptibility profile of the antibiotics used for this purpose, due to the continuous appearance of resistant strains, which makes it difficult to predict the efficacy of any molecule without prior evaluation. Tildipirosin is a last generation macrolide that has been recently used in pigs in Brazil, and its chemical structure is aimed at hindering the emergence of bacterial resistance. Due to the importance of continuous evaluation of antibiotics against bacteria able to trigger diseases in pigs, here, we have evaluated the susceptibility profile of 100 clinical strains of H. parasuis to tildipirosin. All strains included in this study were isolated from pigs with Glässer's disease. From the total, 58 strains were isolated from systemic sites (joints, peritoneum, pericardium and brain) and 42 were recovered from lung tissue. Each strain represents an individual clinical case of GD. The tildipirosin susceptibility test was carried out using the broth microdilution technique, evaluating the minimum inhibitory concentration (MIC) of the product (0.03 - 256 μg / ml). Our results demonstrate that in general the clinical strains of H. parasuis are susceptible to tildipirosin, with MIC50 and MIC90 of 0.25 and 32 μg / ml, respectively. The tildipirosin susceptibility analysis relative to the sample isolation site showed that the strains from systemic sites presented a MIC50 (0.25 μg/ml) higher than those observed in strains of pulmonary origin (0.12 μg/ml). Taking into account the maximum tissue concentration of tildipirosin after parenteral administration of the therapeutic dose (4 mg / kg) of the commercial product Zuprevo® (MSD, Brazil), 72% of the strains could be potentially affected. A small dose adjustment taking into consideration the MICs values could increase the breadth of the efficacy of the product. However, it would not be sufficient to treat 8% of the strains, which have been shown to be highly resistant to the tildipirosin. In summary, our results indicate that tildipirosin may be recommended for the clinical treatment of pigs suffering Glässer's disease, however, because of the presence of strains already resistant to the antibiotic, the MIC test should be periodically used to (i) determine the therapeutic dos e and (ii) monitoring the H. parasuis susceptibility profile to tildipirosin.A cadeia produtiva de carne suína é uma das mais importantes no Brasil e progressivamente vem se desenvolvendo, atualizando e se destacando em nível mundial. Entre os desafios sanitários de maior importância para a suinocultura industrial destacam-se as doenças respiratória, as quais são altamente transmissíveis dentro de uma unidade de produção. Entre os patógenos relacionados com o complexo respiratório suíno, o Haemophilus parasuis (Hps) emerge como um dos principais, acometendo especialmente leitões nas fases de creche e gerando importantes perdas econômicas para a indústria. A vacinação destaca-se como a principal forma de prevenção da doença, porém as atuais vacinas comerciais não garantem imunidade cruzada protetora em razão da alta variabilidade fenotípica das cepas clínicas. Consequentemente, falhas de proteção ocorrem especialmente quando a granja está infectada com um sorovar diferente daquele contido na vacina. Assim, torna-se indispensável o uso de antimicrobianos para tratar os animais doentes, como também o monitoramento periódico dos antibióticos utilizados com este propósito, em razão do contínuo aparecimento de cepas resistentes, o que dificulta predizer a eficácia de qualquer molécula sem uma avaliação prévia. A tildipirosina é um macrolídeo de última geração que começou a ser utilizada recentemente em suínos no Brasil, e sua estrutura química visa dificultar a emergência de resistência bacteriana. Em razão da importância da contínua avaliação de antibióticos contra bactérias de interesse na suinocultura, nesta dissertação, avaliamos o perfil de susceptibilidade de 100 cepas clínicas de H. parasuis a tildipirosina. Todas as cepas foram isoladas de suínos com doença de Glässer, sendo 58 procedentes de sítios sistêmicos (articulação, peritônio, pericárdio e cérebro) e 42 recuperadas do tecido pulmonar. Cada cepa representa um caso clínico individual de GD. O teste de susceptibilidade à tildipirosina foi realizado pela técnica de microdiluição em caldo, avaliando-se a concentração inibitória mínima (MIC) do produto (0.03 - 256 g/ml). Nossos resultados demonstram que em geral as cepas clínicas de H. parasuis apresentam sensibilidade a tildipirosina, com MIC50 e MIC90 de 0.25 e 32g/ml, respectivamente. Na análise de susceptibilidade em relação ao sítio de isolamento da amostra, observamos que as cepas de origem sistêmica apresentaram CMI50 (0.25g/ml) superiores as observadas nas cepas de origem pulmonar (0.12 g/ml). Levando em consideração a concentração tecidual máxima da tildipirosina a partir da administração em suínos da dose terapêutica (4 mg/kg) do produto comercial Zuprevo® (MSD, Brasil), 72% das cepas poderiam ser eficientemente combatidas. Um pequeno ajuste de dose, a partir das MICs encontradas, poderia aumentar a amplitude de eficácia do produto. No entanto, não seria suficiente para combater 8% cepas, as quais demonstraram-se altamente resistentes ao antibiótico. Em síntese, nossos resultados indicam que tildipirosina pode ser recomendada para o tratamento clínico de suínos com doença de Glässer, no entanto, em razão da presença de cepas já resistentes ao antibiótico, o teste de MIC deve ser periodicamente utilizado para (i) determinar a dose terapêutica e (ii) monitorar a evolução de resistência de H. parasuis a tildipirosina.Submitted by Aline Rezende (alinerezende@upf.br) on 2019-07-08T11:38:23Z No. of bitstreams: 1 2018PriscilaPerez.pdf: 525206 bytes, checksum: 1106f7fecc9a1e67f1a159d52a6c72e5 (MD5)Made available in DSpace on 2019-07-08T11:38:23Z (GMT). No. of bitstreams: 1 2018PriscilaPerez.pdf: 525206 bytes, checksum: 1106f7fecc9a1e67f1a159d52a6c72e5 (MD5) Previous issue date: 2018-09-28application/pdfporUniversidade de Passo FundoPrograma de Pós-Graduação em BioexperimentaçãoUPFBrasilFaculdade de Agronomia e Medicina Veterinária – FAMVSuíno - DoençasAntibióticos em veterinária - ControleDiagnóstico bacteriológicoCIENCIAS AGRARIAS::MEDICINA VETERINARIAAtividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuisIn vitro activity of tildipirosin against clinical strains of haemophilus parasuisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis79452006251700495950050060053202200503672799453670264235017319info:eu-repo/semantics/openAccessreponame:Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF)instname:Universidade de Passo Fundo (UPF)instacron:UPFORIGINAL2018PriscilaPerez.pdf2018PriscilaPerez.pdfapplication/pdf525206http://tede.upf.br:8080/jspui/bitstream/tede/1727/2/2018PriscilaPerez.pdf1106f7fecc9a1e67f1a159d52a6c72e5MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://tede.upf.br:8080/jspui/bitstream/tede/1727/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/17272019-07-08 08:38:23.667oai:tede.upf.br:tede/1727Tk9UQTogQ09MT1FVRSBBUVVJIEEgU1VBIFBSw5NQUklBIExJQ0VOw4dBCkVzdGEgbGljZW7Dp2EgZGUgZXhlbXBsbyDDqSBmb3JuZWNpZGEgYXBlbmFzIHBhcmEgZmlucyBpbmZvcm1hdGl2b3MuCgpMSUNFTsOHQSBERSBESVNUUklCVUnDh8ODTyBOw4NPLUVYQ0xVU0lWQQoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSDDoCBVbml2ZXJzaWRhZGUgClhYWCAoU2lnbGEgZGEgVW5pdmVyc2lkYWRlKSBvIGRpcmVpdG8gbsOjby1leGNsdXNpdm8gZGUgcmVwcm9kdXppciwgIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IApkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlIAplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBwb2RlLCBzZW0gYWx0ZXJhciBvIGNvbnRlw7pkbywgdHJhbnNwb3IgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIApwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIHRhbWLDqW0gY29uY29yZGEgcXVlIGEgU2lnbGEgZGUgVW5pdmVyc2lkYWRlIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPDs3BpYSBhIHN1YSB0ZXNlIG91IApkaXNzZXJ0YcOnw6NvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcyAKbmVzdGEgbGljZW7Dp2EuIFZvY8OqIHRhbWLDqW0gZGVjbGFyYSBxdWUgbyBkZXDDs3NpdG8gZGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBuw6NvLCBxdWUgc2VqYSBkZSBzZXUgCmNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiAKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc8OjbyBpcnJlc3RyaXRhIGRvIGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBwYXJhIGNvbmNlZGVyIMOgIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSAKb3MgZGlyZWl0b3MgYXByZXNlbnRhZG9zIG5lc3RhIGxpY2Vuw6dhLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlIAppZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250ZcO6ZG8gZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFRFU0UgT1UgRElTU0VSVEHDh8ODTyBPUkEgREVQT1NJVEFEQSBURU5IQSBTSURPIFJFU1VMVEFETyBERSBVTSBQQVRST0PDjU5JTyBPVSAKQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PIFFVRSBOw4NPIFNFSkEgQSBTSUdMQSBERSAKVU5JVkVSU0lEQURFLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyAKVEFNQsOJTSBBUyBERU1BSVMgT0JSSUdBw4fDlUVTIEVYSUdJREFTIFBPUiBDT05UUkFUTyBPVSBBQ09SRE8uCgpBIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIChzKSBvdSBvKHMpIG5vbWUocykgZG8ocykgCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgo=Biblioteca Digital de Teses e DissertaçõesPUBhttp://tede.upf.br/oai/requestbiblio@upf.br || bio@upf.br || cas@upf.br || car@upf.br || lve@upf.br || sar@upf.br || sol@upf.br || upfmundi@upf.br || jucelei@upf.bropendoar:2019-07-08T11:38:23Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF) - Universidade de Passo Fundo (UPF)false
dc.title.por.fl_str_mv Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
dc.title.alternative.eng.fl_str_mv In vitro activity of tildipirosin against clinical strains of haemophilus parasuis
title Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
spellingShingle Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
Peres, Priscila Rodrigues
Suíno - Doenças
Antibióticos em veterinária - Controle
Diagnóstico bacteriológico
CIENCIAS AGRARIAS::MEDICINA VETERINARIA
title_short Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
title_full Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
title_fullStr Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
title_full_unstemmed Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
title_sort Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis
author Peres, Priscila Rodrigues
author_facet Peres, Priscila Rodrigues
author_role author
dc.contributor.advisor1.fl_str_mv Frandoloso, Rafael
dc.contributor.advisor1ID.fl_str_mv 03912065918
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2502891354017410
dc.contributor.authorID.fl_str_mv 00821198050
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8743231875258102
dc.contributor.author.fl_str_mv Peres, Priscila Rodrigues
contributor_str_mv Frandoloso, Rafael
dc.subject.por.fl_str_mv Suíno - Doenças
Antibióticos em veterinária - Controle
Diagnóstico bacteriológico
topic Suíno - Doenças
Antibióticos em veterinária - Controle
Diagnóstico bacteriológico
CIENCIAS AGRARIAS::MEDICINA VETERINARIA
dc.subject.cnpq.fl_str_mv CIENCIAS AGRARIAS::MEDICINA VETERINARIA
description The pork production chain is one of the most important sectors in Brazil and it is continuously in progress in order to get high development, updating and global recognition. The respiratory diseases of swine are considered a high animal health challenge for industrial pig farms since they can be highly transmissible within a production unit. Amongst the pathogens related to the swine respiratory complex, Haemophilus parasuis has emerged as one of the most important and it affects piglets mainly in the nursery phases producing important economic losses for the industry. Vaccination stands out as the main form of prevent Glässer’s disease (GD), but the current commercial vaccines do not guarantee protective cross-immunity due to the high phenotypic variability of the clinical strains of H. parasuis. Consequently, protection failures occur especially when the farm is infected with a serovar different from those contained in the vaccine. Thus, the use of antimicrobials to treat diseased animals is essential, as is the surveillance of the susceptibility profile of the antibiotics used for this purpose, due to the continuous appearance of resistant strains, which makes it difficult to predict the efficacy of any molecule without prior evaluation. Tildipirosin is a last generation macrolide that has been recently used in pigs in Brazil, and its chemical structure is aimed at hindering the emergence of bacterial resistance. Due to the importance of continuous evaluation of antibiotics against bacteria able to trigger diseases in pigs, here, we have evaluated the susceptibility profile of 100 clinical strains of H. parasuis to tildipirosin. All strains included in this study were isolated from pigs with Glässer's disease. From the total, 58 strains were isolated from systemic sites (joints, peritoneum, pericardium and brain) and 42 were recovered from lung tissue. Each strain represents an individual clinical case of GD. The tildipirosin susceptibility test was carried out using the broth microdilution technique, evaluating the minimum inhibitory concentration (MIC) of the product (0.03 - 256 μg / ml). Our results demonstrate that in general the clinical strains of H. parasuis are susceptible to tildipirosin, with MIC50 and MIC90 of 0.25 and 32 μg / ml, respectively. The tildipirosin susceptibility analysis relative to the sample isolation site showed that the strains from systemic sites presented a MIC50 (0.25 μg/ml) higher than those observed in strains of pulmonary origin (0.12 μg/ml). Taking into account the maximum tissue concentration of tildipirosin after parenteral administration of the therapeutic dose (4 mg / kg) of the commercial product Zuprevo® (MSD, Brazil), 72% of the strains could be potentially affected. A small dose adjustment taking into consideration the MICs values could increase the breadth of the efficacy of the product. However, it would not be sufficient to treat 8% of the strains, which have been shown to be highly resistant to the tildipirosin. In summary, our results indicate that tildipirosin may be recommended for the clinical treatment of pigs suffering Glässer's disease, however, because of the presence of strains already resistant to the antibiotic, the MIC test should be periodically used to (i) determine the therapeutic dos e and (ii) monitoring the H. parasuis susceptibility profile to tildipirosin.
publishDate 2018
dc.date.issued.fl_str_mv 2018-09-28
dc.date.accessioned.fl_str_mv 2019-07-08T11:38:23Z
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dc.identifier.citation.fl_str_mv PERES, Priscila Rodrigues Priscila Rodrigues. Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis. 2018. 64 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2018.
dc.identifier.uri.fl_str_mv http://tede.upf.br:8080/jspui/handle/tede/1727
identifier_str_mv PERES, Priscila Rodrigues Priscila Rodrigues. Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis. 2018. 64 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2018.
url http://tede.upf.br:8080/jspui/handle/tede/1727
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dc.publisher.initials.fl_str_mv UPF
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Faculdade de Agronomia e Medicina Veterinária – FAMV
publisher.none.fl_str_mv Universidade de Passo Fundo
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