Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/29595 |
Resumo: | Systemic Arterial Hypertension is a chronic, non-communicable disease of multifactorial etiology. The sedentary lifestyle associated with a food context rich in saturated fatty acids (SFA) and sugars culminates in dyslipidemia, which can favor the development of SAH. In turn, SAH developed in a dyslipidemic setting is associated with qualitative and quantitative changes in the intestinal microbiome, characterizing intestinal dysbiosis. Systemic alterations appear together with intestinal dysbiosis, such as increased oxidative stress, inflammation and sympathetic hyperactivity, reflecting higher levels of blood pressure (BP). The intestinal microbiome can be recovered from the inoculation of bacteria with probiotic potential and this intestinal modulation can affect BP control organs, as in previous experimental studies probiotics attenuated the autonomic dysfunction and in clinical studies they reduced risk factors for cardiovascular diseases. Limosiactobacillus fermentum strains showed good probiotic characteristics (aggregation, antagonism, adhesion, among others) and exerted a lipid-lowering role in rats, however, their role in cardiovascular and metabolic disorders has not been studied. Therefore, the present study investigated the effects of administering a probiotic formulation of L. fermentum (strains 139, 263 and 296) on cardiorespiratory and metabolic parameters and changes in the intestinal microbiota of rats at 90 days fed a diet rich in AGS . Wistar rats (n=18) adults aged 90 days were fed either a control diet (CTL) or a diet rich in AGS (high-fat diet, HFD). The animals were divided into 3 groups: control group (CTL: n=6); group diet rich in AGS + probiotic formulation of L. fermentum 139, 263 and 296 (HFD-LF: n=6); High AGS diet group (HFD: n=6). The administration of L. fermentum strains (109 CFU/mL of each strain) was performed daily via gavage from the 90th to the 120th day of life. On the 120th day of life, feces were collected for analysis of fecal microbiota, blood samples were quantified total cholesterol (TC), high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), triglycerides ( TG) and the insulin tolerance test (TII) was performed. Cardiovascular parameters were obtained from the recording of BP and heart rate (HR) at baseline levels and after administration of hexamethonium (a sympathetic nervous system ganglion blocker; dosage of 25mg/kg) to assess the contribution of sympathetic tone. The variability of HR and BP was evaluated under baseline conditions. The HFD-LF group had lower serum levels of TG, TC and LDL-cholesterol, higher plasma concentration of HDL-cholesterol and smaller area under the TII curve after receiving the treatment with the probiotic formulation of L. fermentum for 4 weeks, when compared to the HFD group (p<0.05). The BP levels were lower in the HFDLF group compared to the HFD group (p<0.05), but with no change in HR (p>0.05). In the spectral analysis, the probiotic formulation with L. fermentum prevented an increase in the LF oscillations of the systolic blood pressure (SBP) and the LH/HF ratio of the cardiac interval of the HFD-LF group (p<0.05) compared to the HFD group. However, the treatment did not interfere with HF oscillations and spontaneous baroreflex sensitivity compared to the HFD group (p>0.05). After administration of hexamethonium, the increase in vasomotor tone was prevented in animals from the HFD-LF group compared to the HFD group (p<0.05). Considering the composition of the intestinal microbiota, low richness and low diversity were found in the HFD-LF group in relation to the CTL. In the HFD group, the AGS-rich diet increased the relative abundance of bacteria that impair intestinal integrity, such as the Enterobacteriales and Campylobacterales orders, the Clostridiaceae, Peptostreptococcaceae families and showed a positive correlation with the Ruminococcus torques and Ruminococcus gnavus species, which also impair intestinal barrier function. In addition, the AGS-rich diet reduced the relative abundance of bacteria that favor intestinal integrity, such as the Lachnospiraceae families, other Ruminococcaceae species, Erysipelotrichaceae, and the orders Mollicutes RF39, Gastranaerophilales from the HFD group compared to the CTL group. After the administration of L. fermentum, a lower abundance of bacteria that affect the intestinal microbiome Campylobacterales, Helicobacteraceae and a negative correlation with Ruminococcus gnavus and Ruminococcus torques was found. A positive correlation was found with bacteria that strengthen the intestinal barrier, such as Ruminococcaceae_UCG-004. Treatment with L. fermentum probiotic formulation improved the composition of the intestinal microbiota, attenuated disorders in the lipid profile, prevented insulin resistance and sympathetic hyperactivity in rats fed a diet rich in AGS. |
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Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratosDislipidemiaProbióticosMicrobiota intestinalHiperatividade simpáticaDyslipidemiaProbioticsIntestinal microbiotaSympathetic hyperactivityArterial hypertensionCNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIASystemic Arterial Hypertension is a chronic, non-communicable disease of multifactorial etiology. The sedentary lifestyle associated with a food context rich in saturated fatty acids (SFA) and sugars culminates in dyslipidemia, which can favor the development of SAH. In turn, SAH developed in a dyslipidemic setting is associated with qualitative and quantitative changes in the intestinal microbiome, characterizing intestinal dysbiosis. Systemic alterations appear together with intestinal dysbiosis, such as increased oxidative stress, inflammation and sympathetic hyperactivity, reflecting higher levels of blood pressure (BP). The intestinal microbiome can be recovered from the inoculation of bacteria with probiotic potential and this intestinal modulation can affect BP control organs, as in previous experimental studies probiotics attenuated the autonomic dysfunction and in clinical studies they reduced risk factors for cardiovascular diseases. Limosiactobacillus fermentum strains showed good probiotic characteristics (aggregation, antagonism, adhesion, among others) and exerted a lipid-lowering role in rats, however, their role in cardiovascular and metabolic disorders has not been studied. Therefore, the present study investigated the effects of administering a probiotic formulation of L. fermentum (strains 139, 263 and 296) on cardiorespiratory and metabolic parameters and changes in the intestinal microbiota of rats at 90 days fed a diet rich in AGS . Wistar rats (n=18) adults aged 90 days were fed either a control diet (CTL) or a diet rich in AGS (high-fat diet, HFD). The animals were divided into 3 groups: control group (CTL: n=6); group diet rich in AGS + probiotic formulation of L. fermentum 139, 263 and 296 (HFD-LF: n=6); High AGS diet group (HFD: n=6). The administration of L. fermentum strains (109 CFU/mL of each strain) was performed daily via gavage from the 90th to the 120th day of life. On the 120th day of life, feces were collected for analysis of fecal microbiota, blood samples were quantified total cholesterol (TC), high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), triglycerides ( TG) and the insulin tolerance test (TII) was performed. Cardiovascular parameters were obtained from the recording of BP and heart rate (HR) at baseline levels and after administration of hexamethonium (a sympathetic nervous system ganglion blocker; dosage of 25mg/kg) to assess the contribution of sympathetic tone. The variability of HR and BP was evaluated under baseline conditions. The HFD-LF group had lower serum levels of TG, TC and LDL-cholesterol, higher plasma concentration of HDL-cholesterol and smaller area under the TII curve after receiving the treatment with the probiotic formulation of L. fermentum for 4 weeks, when compared to the HFD group (p<0.05). The BP levels were lower in the HFDLF group compared to the HFD group (p<0.05), but with no change in HR (p>0.05). In the spectral analysis, the probiotic formulation with L. fermentum prevented an increase in the LF oscillations of the systolic blood pressure (SBP) and the LH/HF ratio of the cardiac interval of the HFD-LF group (p<0.05) compared to the HFD group. However, the treatment did not interfere with HF oscillations and spontaneous baroreflex sensitivity compared to the HFD group (p>0.05). After administration of hexamethonium, the increase in vasomotor tone was prevented in animals from the HFD-LF group compared to the HFD group (p<0.05). Considering the composition of the intestinal microbiota, low richness and low diversity were found in the HFD-LF group in relation to the CTL. In the HFD group, the AGS-rich diet increased the relative abundance of bacteria that impair intestinal integrity, such as the Enterobacteriales and Campylobacterales orders, the Clostridiaceae, Peptostreptococcaceae families and showed a positive correlation with the Ruminococcus torques and Ruminococcus gnavus species, which also impair intestinal barrier function. In addition, the AGS-rich diet reduced the relative abundance of bacteria that favor intestinal integrity, such as the Lachnospiraceae families, other Ruminococcaceae species, Erysipelotrichaceae, and the orders Mollicutes RF39, Gastranaerophilales from the HFD group compared to the CTL group. After the administration of L. fermentum, a lower abundance of bacteria that affect the intestinal microbiome Campylobacterales, Helicobacteraceae and a negative correlation with Ruminococcus gnavus and Ruminococcus torques was found. A positive correlation was found with bacteria that strengthen the intestinal barrier, such as Ruminococcaceae_UCG-004. Treatment with L. fermentum probiotic formulation improved the composition of the intestinal microbiota, attenuated disorders in the lipid profile, prevented insulin resistance and sympathetic hyperactivity in rats fed a diet rich in AGS.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqA Hipertensão Arterial Sistêmica é uma doença crônica não transmissível de etiologia multifatorial. O estilo de vida sedentário associado à um contexto alimentar rico em ácidos graxos saturados (AGS) e açúcares culmina em dislipidemias, as quais podem favorecer o desenvolvimento da HAS. Por sua vez, a HAS desenvolvida em um quadro dislipidêmico é associada com alterações qualitativas e quantitativas do microbioma intestinal, caracterizando a disbiose intestinal. Alterações sistêmicas surgem junto à disbiose intestinal, como o aumento do estresse oxidativo, inflamação e hiperatividade simpática, refletindo em maiores níveis de pressão arterial (PA). O microbioma intestinal pode ser recuperado a partir da inoculação de bactérias com potencial probiótico e essa modulação intestinal pode afetar órgãos de controle da PA, visto que em estudos experimentais anteriores probióticos atenuaram a disfunção autonômica e em estudos clínicos reduziram fatores de risco para doenças cardiovasculares. Cepas de Limosiactobacillus fermentum apresentaram boas características probióticas (agregação, antagonismo, adesão, entre outras) e exerceram papel hipolipemiante em ratos, no entanto a atuação em distúrbios cardiovasculares e metabólicos não foi estudada. Por isso, o presente estudo investigou os efeitos da administração de uma formulação probiótica de L. fermentum (cepas 139, 263 e 296) sobre os parâmetros cardiorrespiratórios, metabólicos e alterações na microbiota intestinal de ratos aos 90 dias alimentados com uma dieta rica em AGS. Ratos Wistar (n=18) adultos com 90 dias foram alimentados com dieta controle (CTL) ou dieta rica em AGS (high-fat diet, HFD). Os animais foram divididos em 3 grupos: grupo controle (CTL: n=6); grupo dieta rica em AGS + formulação probiótica de L. fermentum 139, 263 e 296 (HFD-LF: n=6); grupo dieta rica em AGS (HFD: n=6). A administração das cepas de L. fermentum (109 UFC/mL de cada cepa) foi realizada diariamente via gavagem do 90º ao 120º dia de vida. Ao 120º dia de vida, as fezes foram coletadas para análise da microbiota fecal, nas amostras de sangue foram quantificados colesterol total (CT), lipoproteína de alta densidade (HDL-colesterol), lipoproteína de baixa densidade (LDL-colesterol), triglicerídeos (TG) e foi feito o teste de tolerância à insulina (TII). Parâmetros cardiovasculares foram obtidos a partir do registro da PA e da frequência cardíaca (FC) em níveis basais e após administração de hexametônio (fármaco bloqueador ganglionar do sistema nervoso simpático; dosagem 25mg/kg) para avaliar a contribuição do tônus simpático. A variabilidade da FC e PA foi avaliada em condições basais. O grupo HFD-LF apresentou níveis séricos de TG, CT e LDL-colesterol menores, maior concentração plasmática de HDL-colesterol e menor área sob a curva do TII após receber o tratamento da formulação probiótica de L. fermentum por 4 semanas, quando comparado ao grupo HFD (p<0.05). Os níveis de PA foram menores no grupo HFD-LF em relação ao grupo HFD (p<0.05), mas sem alteração da FC (p>0.05). Na análise espectral, a formulação probiótica com L. fermentum preveniu um aumento nas oscilações de LF da pressão arterial sistólica (PAS) e a razão LH/HF do intervalo cardíaco do grupo HFD-LF (p<0.05) em relação ao grupo HFD. No entanto, o tratamento não interferiu em oscilações de HF e na sensibilidade espontânea do barorreflexo em comparação ao grupo HFD (p>0.05). Após administração do hexametônio, o aumento do tônus vasomotor foi prevenido nos animais do grupo HFD-LF em relação ao grupo HFD (p<0.05). Considerando a composição da microbiota intestinal, foi encontrada baixa riqueza e baixa diversidade no grupo HFD-LF em relação ao CTL. No grupo HFD, a dieta rica em AGS aumentou a abundância relativa de bactérias que prejudicam integridade intestinal, como as ordens Enterobacteriales, e Campylobacterales, as famílias Clostridiaceae, Peptostreptococcaceae e demonstrou uma correlação positiva com as espécies Ruminococcus torques e Ruminococcus gnavus, as quais também prejudicam a função de barreira intestinal. Em adição, a dieta rica em AGS reduziu a abundância relativa de bactérias que favorecem a integridade intestinal, como as famílias Lachnospiraceae, outras espécies de Ruminococcaceae, Erysipelotrichaceae, e as ordens Mollicutes RF39, Gastranaerophilales do grupo HFD em relação ao grupo CTL. Após a administração de L. fermentum foi encontrada menor abundância de bactérias que afetam o microbioma intestinal Campylobacterales, Helicobacteraceae e correlação negativa com Ruminococcus gnavus e Ruminococcus torques. Foi encontrada correlação positiva com bactérias que fortalecem a barreira intestinal, como Ruminococcaceae_UCG-004. O tratamento com formulação probiótica de L. fermentum melhorou a composição da microbiota intestinal, atenuou desordens no perfil lipídico, preveniu a resistência à insulina e a hiperatividade simpática em ratos alimentados com uma dieta rica em AGS.Universidade Federal da ParaíbaBrasilCiências FisiológicasPrograma Multicêntrico de Pós-Graduação em Ciências FisiológicasUFPBAlves, José Luiz de Britohttp://lattes.cnpq.br/6771368391025310Ferreira, Georgianna de Araújo Henriques2024-02-22T14:04:24Z2023-07-272024-02-22T14:04:24Z2021-08-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/29595porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2024-02-23T06:04:11Zoai:repositorio.ufpb.br:123456789/29595Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2024-02-23T06:04:11Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
title |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
spellingShingle |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos Ferreira, Georgianna de Araújo Henriques Dislipidemia Probióticos Microbiota intestinal Hiperatividade simpática Dyslipidemia Probiotics Intestinal microbiota Sympathetic hyperactivity Arterial hypertension CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
title_full |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
title_fullStr |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
title_full_unstemmed |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
title_sort |
Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos |
author |
Ferreira, Georgianna de Araújo Henriques |
author_facet |
Ferreira, Georgianna de Araújo Henriques |
author_role |
author |
dc.contributor.none.fl_str_mv |
Alves, José Luiz de Brito http://lattes.cnpq.br/6771368391025310 |
dc.contributor.author.fl_str_mv |
Ferreira, Georgianna de Araújo Henriques |
dc.subject.por.fl_str_mv |
Dislipidemia Probióticos Microbiota intestinal Hiperatividade simpática Dyslipidemia Probiotics Intestinal microbiota Sympathetic hyperactivity Arterial hypertension CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
topic |
Dislipidemia Probióticos Microbiota intestinal Hiperatividade simpática Dyslipidemia Probiotics Intestinal microbiota Sympathetic hyperactivity Arterial hypertension CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
Systemic Arterial Hypertension is a chronic, non-communicable disease of multifactorial etiology. The sedentary lifestyle associated with a food context rich in saturated fatty acids (SFA) and sugars culminates in dyslipidemia, which can favor the development of SAH. In turn, SAH developed in a dyslipidemic setting is associated with qualitative and quantitative changes in the intestinal microbiome, characterizing intestinal dysbiosis. Systemic alterations appear together with intestinal dysbiosis, such as increased oxidative stress, inflammation and sympathetic hyperactivity, reflecting higher levels of blood pressure (BP). The intestinal microbiome can be recovered from the inoculation of bacteria with probiotic potential and this intestinal modulation can affect BP control organs, as in previous experimental studies probiotics attenuated the autonomic dysfunction and in clinical studies they reduced risk factors for cardiovascular diseases. Limosiactobacillus fermentum strains showed good probiotic characteristics (aggregation, antagonism, adhesion, among others) and exerted a lipid-lowering role in rats, however, their role in cardiovascular and metabolic disorders has not been studied. Therefore, the present study investigated the effects of administering a probiotic formulation of L. fermentum (strains 139, 263 and 296) on cardiorespiratory and metabolic parameters and changes in the intestinal microbiota of rats at 90 days fed a diet rich in AGS . Wistar rats (n=18) adults aged 90 days were fed either a control diet (CTL) or a diet rich in AGS (high-fat diet, HFD). The animals were divided into 3 groups: control group (CTL: n=6); group diet rich in AGS + probiotic formulation of L. fermentum 139, 263 and 296 (HFD-LF: n=6); High AGS diet group (HFD: n=6). The administration of L. fermentum strains (109 CFU/mL of each strain) was performed daily via gavage from the 90th to the 120th day of life. On the 120th day of life, feces were collected for analysis of fecal microbiota, blood samples were quantified total cholesterol (TC), high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), triglycerides ( TG) and the insulin tolerance test (TII) was performed. Cardiovascular parameters were obtained from the recording of BP and heart rate (HR) at baseline levels and after administration of hexamethonium (a sympathetic nervous system ganglion blocker; dosage of 25mg/kg) to assess the contribution of sympathetic tone. The variability of HR and BP was evaluated under baseline conditions. The HFD-LF group had lower serum levels of TG, TC and LDL-cholesterol, higher plasma concentration of HDL-cholesterol and smaller area under the TII curve after receiving the treatment with the probiotic formulation of L. fermentum for 4 weeks, when compared to the HFD group (p<0.05). The BP levels were lower in the HFDLF group compared to the HFD group (p<0.05), but with no change in HR (p>0.05). In the spectral analysis, the probiotic formulation with L. fermentum prevented an increase in the LF oscillations of the systolic blood pressure (SBP) and the LH/HF ratio of the cardiac interval of the HFD-LF group (p<0.05) compared to the HFD group. However, the treatment did not interfere with HF oscillations and spontaneous baroreflex sensitivity compared to the HFD group (p>0.05). After administration of hexamethonium, the increase in vasomotor tone was prevented in animals from the HFD-LF group compared to the HFD group (p<0.05). Considering the composition of the intestinal microbiota, low richness and low diversity were found in the HFD-LF group in relation to the CTL. In the HFD group, the AGS-rich diet increased the relative abundance of bacteria that impair intestinal integrity, such as the Enterobacteriales and Campylobacterales orders, the Clostridiaceae, Peptostreptococcaceae families and showed a positive correlation with the Ruminococcus torques and Ruminococcus gnavus species, which also impair intestinal barrier function. In addition, the AGS-rich diet reduced the relative abundance of bacteria that favor intestinal integrity, such as the Lachnospiraceae families, other Ruminococcaceae species, Erysipelotrichaceae, and the orders Mollicutes RF39, Gastranaerophilales from the HFD group compared to the CTL group. After the administration of L. fermentum, a lower abundance of bacteria that affect the intestinal microbiome Campylobacterales, Helicobacteraceae and a negative correlation with Ruminococcus gnavus and Ruminococcus torques was found. A positive correlation was found with bacteria that strengthen the intestinal barrier, such as Ruminococcaceae_UCG-004. Treatment with L. fermentum probiotic formulation improved the composition of the intestinal microbiota, attenuated disorders in the lipid profile, prevented insulin resistance and sympathetic hyperactivity in rats fed a diet rich in AGS. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-25 2023-07-27 2024-02-22T14:04:24Z 2024-02-22T14:04:24Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/29595 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/29595 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Ciências Fisiológicas Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Ciências Fisiológicas Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas UFPB |
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reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
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UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801843027714506752 |