Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/18016 |
Resumo: | Introduction: Sickle cell disease is a group of hematological genetic diseases, which leads to a mutation in the β-globin gene, in a new type of hemoglobin, hemoglobin S (HbS). The sickle-cell anemia (SCA; HbSS) genotype is the greatest severity form of the disease. The formation of hemoglobin polymers and structural changes in the red blood cells lead to chronic hemolysis and vaso-occlusive episodes.Hepcidin is the key hormone in the regulation of iron metabolism and acts to reduce iron absorption and bioavailability. Hemolysis, anemia, hypoxia, and increased erythropoiesis can reduce the transcription of the hepcidin gene, constituting a counter-regulatory mechanism to increase iron absorption. In contrast, situations of iron overload, inflammation and obesity, are able to increase the transcription of the hepcidin gene, which may lead to lower iron absorption. Studies have linked hepcidin to iron overload. However, most patients with SCA do not present iron overload. Objective: evaluate the predictive factors of plasma hepcidin concentration in individuals with SCA without iron overload. Methods: A database was analyzed with data collected between 2014 and 2016, composed of 101 adult participants (19-59 years old), divided into: group with non-iron overload (serum ferritin <1000 ng / mL) (n = 58); and control group without the disease (n = 43). Hemoglobin (Hb), red blood cells (RBC), hematocrit (Ht), total iron binding capacity (TIBC) and serum iron (Fe) were used as indicators of anemia / hypoxia; growth differentiation factor 15 (GDF-15) and reticulocytes as indicators of erythropoietic activity; lactate dehydrogenase (LDH) as an indicator of hemolysis; ferritin (Ft) and transferrin saturation index (TSI) as indicators of iron loading; interleukin-6 (IL-6) and leukocytes as indicators of inflammation; body mass index (BMI) as an indicator of obesity. To determine the relationship between the variables, multiple linear regression was performed by the backward method, considering hepcidin as a dependent variable. Results: The median serum hepcidin concentration was lower in the SCA group (4.2 ng / mL; Interquartile Interval, IQI: 2.20-7.77 ng / mL) when compared to the control group (7.2 ng / mL;IQI: 5.60-11.60 ng / mL). The determinant variables for serum hepcidin concentration in people with SCA were: Ft (p = 0.0001, β = 0.430), LDH (p = 0.0001, β = -0.634) and reticulocytes (p = 0.002, β = -0.351). For individuals without the disease, the determinants were: Ft (p = 0.018, β = 0.220) and Ht (p = 0.034, β = 1.976). When regression analysis was done with another cutoff for serum ferritin (> 300 ng / mL for males or> 200 ng / mL females), the determinants of hepcidin were: Ft (p = 0.0001, β = 0.457), reticulocytes (p = 0.0001, β = -0.410)and LDH ( p = 0.0001; β = -0.709) in the high ferritin subgroup. In the subgroup with normal serum ferritin, the determinants of hepcidin were:Ft (p = 0.0001, β = 0.458), reticulocytes(p = 0.001, β = -0.481) and LDH (p = 0.001; β = -0.659). Conclusion: Hemolysis seems to explain the lower concentration of serum hepcidin in individuals with SCA without iron overload. At the same time, indicators of iron status correlate with hepcidin concentrations, both in healthy people and people with SCA. |
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Reis, Marta Citelli doshttp://lattes.cnpq.br/1136248028072284Rodrigues, Cláudia dos Santos Coplehttp://lattes.cnpq.br/0681416211288738Fleury, Marcos Kneiphttp://lattes.cnpq.br/2281362757604724Koury, Josely Correahttp://lattes.cnpq.br/9039270525512042http://lattes.cnpq.br/7547741734093450Monteiro, Jessyca Dias Cardoso2022-07-08T14:11:24Z2018-07-26MONTEIRO, Jessyca Dias Cardoso. Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro. 2018. 72 f. Dissertação (Mestrado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018.http://www.bdtd.uerj.br/handle/1/18016Introduction: Sickle cell disease is a group of hematological genetic diseases, which leads to a mutation in the β-globin gene, in a new type of hemoglobin, hemoglobin S (HbS). The sickle-cell anemia (SCA; HbSS) genotype is the greatest severity form of the disease. The formation of hemoglobin polymers and structural changes in the red blood cells lead to chronic hemolysis and vaso-occlusive episodes.Hepcidin is the key hormone in the regulation of iron metabolism and acts to reduce iron absorption and bioavailability. Hemolysis, anemia, hypoxia, and increased erythropoiesis can reduce the transcription of the hepcidin gene, constituting a counter-regulatory mechanism to increase iron absorption. In contrast, situations of iron overload, inflammation and obesity, are able to increase the transcription of the hepcidin gene, which may lead to lower iron absorption. Studies have linked hepcidin to iron overload. However, most patients with SCA do not present iron overload. Objective: evaluate the predictive factors of plasma hepcidin concentration in individuals with SCA without iron overload. Methods: A database was analyzed with data collected between 2014 and 2016, composed of 101 adult participants (19-59 years old), divided into: group with non-iron overload (serum ferritin <1000 ng / mL) (n = 58); and control group without the disease (n = 43). Hemoglobin (Hb), red blood cells (RBC), hematocrit (Ht), total iron binding capacity (TIBC) and serum iron (Fe) were used as indicators of anemia / hypoxia; growth differentiation factor 15 (GDF-15) and reticulocytes as indicators of erythropoietic activity; lactate dehydrogenase (LDH) as an indicator of hemolysis; ferritin (Ft) and transferrin saturation index (TSI) as indicators of iron loading; interleukin-6 (IL-6) and leukocytes as indicators of inflammation; body mass index (BMI) as an indicator of obesity. To determine the relationship between the variables, multiple linear regression was performed by the backward method, considering hepcidin as a dependent variable. Results: The median serum hepcidin concentration was lower in the SCA group (4.2 ng / mL; Interquartile Interval, IQI: 2.20-7.77 ng / mL) when compared to the control group (7.2 ng / mL;IQI: 5.60-11.60 ng / mL). The determinant variables for serum hepcidin concentration in people with SCA were: Ft (p = 0.0001, β = 0.430), LDH (p = 0.0001, β = -0.634) and reticulocytes (p = 0.002, β = -0.351). For individuals without the disease, the determinants were: Ft (p = 0.018, β = 0.220) and Ht (p = 0.034, β = 1.976). When regression analysis was done with another cutoff for serum ferritin (> 300 ng / mL for males or> 200 ng / mL females), the determinants of hepcidin were: Ft (p = 0.0001, β = 0.457), reticulocytes (p = 0.0001, β = -0.410)and LDH ( p = 0.0001; β = -0.709) in the high ferritin subgroup. In the subgroup with normal serum ferritin, the determinants of hepcidin were:Ft (p = 0.0001, β = 0.458), reticulocytes(p = 0.001, β = -0.481) and LDH (p = 0.001; β = -0.659). Conclusion: Hemolysis seems to explain the lower concentration of serum hepcidin in individuals with SCA without iron overload. At the same time, indicators of iron status correlate with hepcidin concentrations, both in healthy people and people with SCA.A doença falciforme é um grupo de doenças genéticas hematológicas, resultantes da mutação no gene da β-globina, gerando um novo tipo de hemoglobina, a hemoglobina S (HbS). Ogenótipo da anemia falciforme (AF; HbSS) é a forma da doençacom maior gravidade dentre os genótipos.A formação de polímeros de hemoglobina e alterações estruturais nas hemácias levamà hemólise crônica e vaso-oclusão. A hepcidina é o hormônio chave na regulação do metabolismo do ferro e atuareduzindo sua absorção e biodisponibilidade. A hemólise, a anemia, a eritropoiese aumentada e a hipóxia podem reduzir a transcrição do gene da hepcidina, sendo um mecanismo contra regulatório paraaumentar a absorção de ferro. Em contrapartida, situações de sobrecarga de ferro, inflamação e obesidade, podem aumentar a transcrição do gene da hepcidina, levandoàredução da absorção deferro. A relação entre hepcidina e sobrecarga de ferro foi observada em estudos em que os pacientes apresentavam sobrecarga de ferro, deixando uma lacuna no conhecimento a respeito dos pacientes que não apresentam tal condição. O objetivo do estudo foiidentificar os fatores preditores da concentração sérica de hepcidina em pessoas comAF sem sobrecarga de ferro. As informações utilizadas foramcoletadas entre os anos de 2014 a 2016. Os participantes foram divididos em dois grupos: com AF sem sobrecarga de ferro (concentração plasmática de ferritina <1000ng/dL – n=58) e grupo controle (n=43) composto por indivíduos aparentemente saudáveis.Hemoglobina (Hb), hemácias (Hm), hematócrito (Ht), capacidade de total de ligação de ferro (CTLF) e ferro sérico (Fe) foram utilizados como indicadores de anemia/hipóxia; fator de diferenciação do crescimento 15 (GDF-15) e contagem de reticulócitos,como indicadores de atividade eritropoiética; lactato desidrogenase (LDH),como indicador dehemólise; ferritina (Ft) e índice de saturação da transferrina (IST), como indicadores da carga corporal de ferro; interleucina-6 (IL-6) e leucócitos, como indicadores de inflamação; índice de massa corporal (IMC), como indicador de obesidade. Para determinar a relação entre as variáveis realizou-se regressão linear múltipla, seguido pelo teste backward, considerando-se a hepcidina como variável dependente.A mediana daconcentração de hepcidina sérica foi menor no grupo com a doença (4,2ng/mL;IIQ: 2,20-7,77ng/mL)comparado ao grupo controle (7,2ng/mL; IIQ:5,60-11,60ng/mL).As variáveis determinantes da concentração de hepcidina sérica em pessoas com AF foram Ft (β=0,430; p=0,0001), LDH (β=-0,634; p=0,0001) e reticulócitos (β=-0,351; p=0,002). Para os indivíduos sem a doença, os determinantes foram Ft (β=0,220; p=0,018) e Ht (β=1,976; p=0,034).Quando feita análise de regressãoutilizando-seoutro ponto de corte para classificação de excesso de ferro (ferritina sérica ≥300 ng/mL para homens ou ≥200 ng/mL mulheres), as variáveis determinantes da hepcidina sérica foram,ferritina (β=0,458, p=0,0001; ), LDH (β=-0,659; p=0,001) e reticulócitos (β=-0,481; p=0,013)para o subgrupo com ferritina normal (n=38). As mesmas variáveis compuseram o modelo para o subgrupo ferritina elevada (n=20 – ferritina β=-0,457e p=0,0001; LDH β=-0,709 ep=0,0001; reticulócitos β=-0,410; p=0,0001).A hemólise parece explicar a menor concentração de hepcidina sérica em indivíduos com AF sem sobrecarga de ferro. Ao mesmo tempo, em indivíduos saudáveis ou com AF, os indicadores do estado corporal de ferro correlacionam-se às concentrações de hepcidina.Submitted by Mariangela CEH/A (marianfig.uerj@gmail.com) on 2022-07-08T14:11:24Z No. of bitstreams: 2 Dissertação - Jessyca Dias Cardoso Monteiro - 2018 - Completa.pdf: 2653187 bytes, checksum: 6e3be7e42e49b1b0cfb277a8da437be6 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2022-07-08T14:11:24Z (GMT). No. of bitstreams: 2 Dissertação - Jessyca Dias Cardoso Monteiro - 2018 - Completa.pdf: 2653187 bytes, checksum: 6e3be7e42e49b1b0cfb277a8da437be6 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-07-26Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Alimentação, Nutrição e SaúdeUERJBrasilCentro Biomédico::Instituto de Nutriçãohttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessSickle cell anemiaHepcidinBody iron statusHemolysisNutriçãoAnemia falciformeHepcidinaEstado de ferro corporalHemóliseCIENCIAS DA SAUDE::NUTRICAO::BIOQUIMICA DA NUTRICAOFatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferroDeterminants of serum hepcidin concentration in patients with sickle cell anemia without iron overloadinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDissertação - Jessyca Dias Cardoso Monteiro - 2018 - Completa.pdfDissertação - Jessyca Dias Cardoso Monteiro - 2018 - Completa.pdfapplication/pdf2653187http://www.bdtd.uerj.br/bitstream/1/18016/5/Disserta%C3%A7%C3%A3o+-+Jessyca+Dias+Cardoso+Monteiro+-+2018+-+Completa.pdf6e3be7e42e49b1b0cfb277a8da437be6MD55CC-LICENSElicense_urllicense_urltext/plain; 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dc.title.por.fl_str_mv |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
dc.title.alternative.eng.fl_str_mv |
Determinants of serum hepcidin concentration in patients with sickle cell anemia without iron overload |
title |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
spellingShingle |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro Monteiro, Jessyca Dias Cardoso Sickle cell anemia Hepcidin Body iron status Hemolysis Nutrição Anemia falciforme Hepcidina Estado de ferro corporal Hemólise CIENCIAS DA SAUDE::NUTRICAO::BIOQUIMICA DA NUTRICAO |
title_short |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
title_full |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
title_fullStr |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
title_full_unstemmed |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
title_sort |
Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro |
author |
Monteiro, Jessyca Dias Cardoso |
author_facet |
Monteiro, Jessyca Dias Cardoso |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Reis, Marta Citelli dos |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1136248028072284 |
dc.contributor.advisor-co1.fl_str_mv |
Rodrigues, Cláudia dos Santos Cople |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/0681416211288738 |
dc.contributor.referee1.fl_str_mv |
Fleury, Marcos Kneip |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2281362757604724 |
dc.contributor.referee2.fl_str_mv |
Koury, Josely Correa |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/9039270525512042 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7547741734093450 |
dc.contributor.author.fl_str_mv |
Monteiro, Jessyca Dias Cardoso |
contributor_str_mv |
Reis, Marta Citelli dos Rodrigues, Cláudia dos Santos Cople Fleury, Marcos Kneip Koury, Josely Correa |
dc.subject.eng.fl_str_mv |
Sickle cell anemia Hepcidin Body iron status Hemolysis |
topic |
Sickle cell anemia Hepcidin Body iron status Hemolysis Nutrição Anemia falciforme Hepcidina Estado de ferro corporal Hemólise CIENCIAS DA SAUDE::NUTRICAO::BIOQUIMICA DA NUTRICAO |
dc.subject.por.fl_str_mv |
Nutrição Anemia falciforme Hepcidina Estado de ferro corporal Hemólise |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::NUTRICAO::BIOQUIMICA DA NUTRICAO |
description |
Introduction: Sickle cell disease is a group of hematological genetic diseases, which leads to a mutation in the β-globin gene, in a new type of hemoglobin, hemoglobin S (HbS). The sickle-cell anemia (SCA; HbSS) genotype is the greatest severity form of the disease. The formation of hemoglobin polymers and structural changes in the red blood cells lead to chronic hemolysis and vaso-occlusive episodes.Hepcidin is the key hormone in the regulation of iron metabolism and acts to reduce iron absorption and bioavailability. Hemolysis, anemia, hypoxia, and increased erythropoiesis can reduce the transcription of the hepcidin gene, constituting a counter-regulatory mechanism to increase iron absorption. In contrast, situations of iron overload, inflammation and obesity, are able to increase the transcription of the hepcidin gene, which may lead to lower iron absorption. Studies have linked hepcidin to iron overload. However, most patients with SCA do not present iron overload. Objective: evaluate the predictive factors of plasma hepcidin concentration in individuals with SCA without iron overload. Methods: A database was analyzed with data collected between 2014 and 2016, composed of 101 adult participants (19-59 years old), divided into: group with non-iron overload (serum ferritin <1000 ng / mL) (n = 58); and control group without the disease (n = 43). Hemoglobin (Hb), red blood cells (RBC), hematocrit (Ht), total iron binding capacity (TIBC) and serum iron (Fe) were used as indicators of anemia / hypoxia; growth differentiation factor 15 (GDF-15) and reticulocytes as indicators of erythropoietic activity; lactate dehydrogenase (LDH) as an indicator of hemolysis; ferritin (Ft) and transferrin saturation index (TSI) as indicators of iron loading; interleukin-6 (IL-6) and leukocytes as indicators of inflammation; body mass index (BMI) as an indicator of obesity. To determine the relationship between the variables, multiple linear regression was performed by the backward method, considering hepcidin as a dependent variable. Results: The median serum hepcidin concentration was lower in the SCA group (4.2 ng / mL; Interquartile Interval, IQI: 2.20-7.77 ng / mL) when compared to the control group (7.2 ng / mL;IQI: 5.60-11.60 ng / mL). The determinant variables for serum hepcidin concentration in people with SCA were: Ft (p = 0.0001, β = 0.430), LDH (p = 0.0001, β = -0.634) and reticulocytes (p = 0.002, β = -0.351). For individuals without the disease, the determinants were: Ft (p = 0.018, β = 0.220) and Ht (p = 0.034, β = 1.976). When regression analysis was done with another cutoff for serum ferritin (> 300 ng / mL for males or> 200 ng / mL females), the determinants of hepcidin were: Ft (p = 0.0001, β = 0.457), reticulocytes (p = 0.0001, β = -0.410)and LDH ( p = 0.0001; β = -0.709) in the high ferritin subgroup. In the subgroup with normal serum ferritin, the determinants of hepcidin were:Ft (p = 0.0001, β = 0.458), reticulocytes(p = 0.001, β = -0.481) and LDH (p = 0.001; β = -0.659). Conclusion: Hemolysis seems to explain the lower concentration of serum hepcidin in individuals with SCA without iron overload. At the same time, indicators of iron status correlate with hepcidin concentrations, both in healthy people and people with SCA. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-07-26 |
dc.date.accessioned.fl_str_mv |
2022-07-08T14:11:24Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MONTEIRO, Jessyca Dias Cardoso. Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro. 2018. 72 f. Dissertação (Mestrado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/18016 |
identifier_str_mv |
MONTEIRO, Jessyca Dias Cardoso. Fatores determinantes da concentração de hepcidina sérica em pacientes com anemia falciforme sem sobrecarga de ferro. 2018. 72 f. Dissertação (Mestrado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
url |
http://www.bdtd.uerj.br/handle/1/18016 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Alimentação, Nutrição e Saúde |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Nutrição |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
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Universidade do Estado do Rio de Janeiro (UERJ) |
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UERJ |
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UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
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Biblioteca Digital de Teses e Dissertações da UERJ |
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http://www.bdtd.uerj.br/bitstream/1/18016/5/Disserta%C3%A7%C3%A3o+-+Jessyca+Dias+Cardoso+Monteiro+-+2018+-+Completa.pdf http://www.bdtd.uerj.br/bitstream/1/18016/2/license_url http://www.bdtd.uerj.br/bitstream/1/18016/3/license_text http://www.bdtd.uerj.br/bitstream/1/18016/4/license_rdf http://www.bdtd.uerj.br/bitstream/1/18016/1/license.txt |
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Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
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bdtd.suporte@uerj.br |
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