Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Lopes, Renata Lima
Orientador(a): Queiroz, José Ajax Nogueira
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/75046
Resumo: Dengue is a viral Dengue is a viral disease that has been worryingly expanding worldwide for decades. In Brazil, dengue is endemic with epidemic peaks. There are some gaps in the understanding of dengue pathogenesis, especially in severe cases leading to death, it continues to be a significant health threat in the affected regions. In vivo studies of human dengue fatal cases can significantly contribute to identifying involved cells in DENV replication, which contributes to thrombocytopenia associated with the severity of dengue. The objective was to identify and quantify lung megakaryocytes, evaluate the correlation between clinical and anatomopathological data with platelets, and identify the presence of NS3 in lung megakaryocytes in cases of severe and fatal dengue fever. A retrospective postmortem observational study was carried out using paraffin blocks of lung tissue from 34 dengue fatal cases occurred in Ceará.All underwent autopsy at the Death Verification Service (SVO) between 2011 and 2013, and all had clinical and laboratory diagnosis of dengue and were duly notified to the Epidemiological Surveillance Center of theCeará Department of Health. The lung tissues were prepared for identification of megakaryocytes by HE stain, immunohistochemistry with anti-CD61 monoclonal antibodies to confirm the identification and quantification of lung megakaryocytes, and demonstration of the indirect presence of viral replication in megakaryocytes with anti-NS3. Lung parenchymal images were captured at 400x magnification, marked with anti-CD61 and anti-NS3 antibodies. A higher average of lung megakaryocytes was found in dengue patients than the control group, presenting a statistically significant difference (5.32 ± 2.69 vs. 2.61 ± 1.97 respectively, p < 0.001). The majority of patients showed bleedingwarning signs (55.88%) and hemorrhage signs at autopsies (91.18%). Regarding thrombotic events, they occurred in 35.29% of fatal dengue cases and 58.33% of thrombotic events were pulmonary. The results also revealed that 38.24% of dengue patients had pulmonary megakaryocytes stained against NS3, confirming the presence of DENV replication in these cells. In summary, it was demonstrated an increase in the number of lung megakaryocytes and the in vivo NS3 expression in lung megakaryocytes from patients with severedengue fever, indicating that DENV can infect these cells, compromising platelet production, therefore contributing to an unfavorable prognosis.
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spelling Lopes, Renata LimaBarroso, Fernanda CapeloQueiroz, José Ajax Nogueira2023-11-23T14:52:21Z2023-11-23T14:52:21Z2023LOPES, Renata Lima. Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica. 2023. Dissertação (Mestrado em Patologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75046. Acesso em: 23 nov. 2023.http://repositorio.ufc.br/handle/riufc/75046Dengue is a viral Dengue is a viral disease that has been worryingly expanding worldwide for decades. In Brazil, dengue is endemic with epidemic peaks. There are some gaps in the understanding of dengue pathogenesis, especially in severe cases leading to death, it continues to be a significant health threat in the affected regions. In vivo studies of human dengue fatal cases can significantly contribute to identifying involved cells in DENV replication, which contributes to thrombocytopenia associated with the severity of dengue. The objective was to identify and quantify lung megakaryocytes, evaluate the correlation between clinical and anatomopathological data with platelets, and identify the presence of NS3 in lung megakaryocytes in cases of severe and fatal dengue fever. A retrospective postmortem observational study was carried out using paraffin blocks of lung tissue from 34 dengue fatal cases occurred in Ceará.All underwent autopsy at the Death Verification Service (SVO) between 2011 and 2013, and all had clinical and laboratory diagnosis of dengue and were duly notified to the Epidemiological Surveillance Center of theCeará Department of Health. The lung tissues were prepared for identification of megakaryocytes by HE stain, immunohistochemistry with anti-CD61 monoclonal antibodies to confirm the identification and quantification of lung megakaryocytes, and demonstration of the indirect presence of viral replication in megakaryocytes with anti-NS3. Lung parenchymal images were captured at 400x magnification, marked with anti-CD61 and anti-NS3 antibodies. A higher average of lung megakaryocytes was found in dengue patients than the control group, presenting a statistically significant difference (5.32 ± 2.69 vs. 2.61 ± 1.97 respectively, p < 0.001). The majority of patients showed bleedingwarning signs (55.88%) and hemorrhage signs at autopsies (91.18%). Regarding thrombotic events, they occurred in 35.29% of fatal dengue cases and 58.33% of thrombotic events were pulmonary. The results also revealed that 38.24% of dengue patients had pulmonary megakaryocytes stained against NS3, confirming the presence of DENV replication in these cells. In summary, it was demonstrated an increase in the number of lung megakaryocytes and the in vivo NS3 expression in lung megakaryocytes from patients with severedengue fever, indicating that DENV can infect these cells, compromising platelet production, therefore contributing to an unfavorable prognosis.A dengue é uma doença viral que vem se expandido mundialmente de forma preocupante nas últimas décadas. No Brasil, a dengue é endêmica com picos epidêmicos. Devido a existência de algumas lacunas na compreensão de sua patogênese, especialmente em casos graves que levam a morte, a dengue continua sendo uma ameaça significativa à saúde nas regiões atingidas. Estudos in vivo de casos fatais humanos podem contribuir de forma significativa para elucidação das células envolvidas na replicação do DENV, contribuindo para a trombocitopenia associada à gravidade da dengue. Objetivou-se identificar e quantificar osmegacariócitos pulmonares, avaliar correlação entre dados clínicos e anatomopatológicos com plaquetas, e identificar a presença de NS3 em megacariócitos pulmonares em casos de dengue grave e fatal. Reazilizou-se um estudo observacional retrospectivo post-mortem, onde foram analisados blocos de parafina de tecido pulmonar de 34 casos de dengue fatal ocorridos no Ceará e que sofreram autópsia no Serviço de Verificação de Óbito (SVO) entre 2011 e 2013 com diagnóstico clínico e laboratorial de dengue devidamente notificados ao Núcleo de Vigilância Epidemiológica da Secretaria de Saúde do estado do Ceará. Os tecidos pulmonares foram preparados para identificação dos megacariócitos na coloração HE, estudo imunohistoquímico com anticorpos monoclonais anti-CD61 para confirmação da identificação e quantificação dos megacariócitos pulmonares, e demonstração da presença indireta da replicação viral nos megacariócitos com anticorpos monoclonais anti-NS3. Foram capturadas imagens na magnificação de 400x do parênquima pulmonar marcadas com anticorpo anti-CD61 e anti-NS3. Encontrou-se uma média maior de megacariócitos pulmonares em pacientes com dengue do que no grupo controle apresentando diferença estatisticamente significante (5,32 ± 2,69 vs. 2,61 ± 1,97 respectivamente p < 0,001). A maioria dos pacientes apresentou sinais de alerta para sangramento (55,88%) e sinais de hemorragia nas autópsias (91,18%). Com relação aos eventos trombóticos, ocorreram em 35,29% dos casos fatais de dengue e 58,33% dos eventos trombóticos foram pulmonares. Os resultados também revelaram que 38,24% dos pacientes com dengue apresentavam megacariócitos pulmonares marcados contra NS3 confirmando a presença de replicação do DENV nessas células. Em suma, demonstrou-se um aumento dos megacariócitos pulmonares, e a expressão,in vivo, de NS3 em megacariócitos pulmonares de pacientes com dengue grave, indicando que o DENV pode infectar essas células comprometendo a produção de plaquetascontribuindo, portanto, para um prognóstico desfavorável.Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológicaStudy of megakaryocytes and NS3 expression in lungs of fatal dengue cases: clinical-pathological associationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisDengue GraveMegacariócitosImuno-HistoquímicaInfecções por ArbovirusPulmãoCNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0003-1655-8095http://lattes.cnpq.br/1638397105510270http://lattes.cnpq.br/6534805938502619http://lattes.cnpq.br/2692445077302258ORIGINAL2023_dis_rllopes.pdf2023_dis_rllopes.pdfapplication/pdf2575007http://repositorio.ufc.br/bitstream/riufc/75046/8/2023_dis_rllopes.pdf002b1b784e88adb900d886d7e324c8dbMD58LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/75046/9/license.txt8a4605be74aa9ea9d79846c1fba20a33MD59riufc/750462023-11-27 07:54:01.152oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-11-27T10:54:01Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
dc.title.en.pt_BR.fl_str_mv Study of megakaryocytes and NS3 expression in lungs of fatal dengue cases: clinical-pathological association
title Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
spellingShingle Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
Lopes, Renata Lima
CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
Dengue Grave
Megacariócitos
Imuno-Histoquímica
Infecções por Arbovirus
Pulmão
title_short Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
title_full Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
title_fullStr Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
title_full_unstemmed Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
title_sort Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica
author Lopes, Renata Lima
author_facet Lopes, Renata Lima
author_role author
dc.contributor.co-advisor.none.fl_str_mv Barroso, Fernanda Capelo
dc.contributor.author.fl_str_mv Lopes, Renata Lima
dc.contributor.advisor1.fl_str_mv Queiroz, José Ajax Nogueira
contributor_str_mv Queiroz, José Ajax Nogueira
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
Dengue Grave
Megacariócitos
Imuno-Histoquímica
Infecções por Arbovirus
Pulmão
dc.subject.ptbr.pt_BR.fl_str_mv Dengue Grave
Megacariócitos
Imuno-Histoquímica
Infecções por Arbovirus
Pulmão
description Dengue is a viral Dengue is a viral disease that has been worryingly expanding worldwide for decades. In Brazil, dengue is endemic with epidemic peaks. There are some gaps in the understanding of dengue pathogenesis, especially in severe cases leading to death, it continues to be a significant health threat in the affected regions. In vivo studies of human dengue fatal cases can significantly contribute to identifying involved cells in DENV replication, which contributes to thrombocytopenia associated with the severity of dengue. The objective was to identify and quantify lung megakaryocytes, evaluate the correlation between clinical and anatomopathological data with platelets, and identify the presence of NS3 in lung megakaryocytes in cases of severe and fatal dengue fever. A retrospective postmortem observational study was carried out using paraffin blocks of lung tissue from 34 dengue fatal cases occurred in Ceará.All underwent autopsy at the Death Verification Service (SVO) between 2011 and 2013, and all had clinical and laboratory diagnosis of dengue and were duly notified to the Epidemiological Surveillance Center of theCeará Department of Health. The lung tissues were prepared for identification of megakaryocytes by HE stain, immunohistochemistry with anti-CD61 monoclonal antibodies to confirm the identification and quantification of lung megakaryocytes, and demonstration of the indirect presence of viral replication in megakaryocytes with anti-NS3. Lung parenchymal images were captured at 400x magnification, marked with anti-CD61 and anti-NS3 antibodies. A higher average of lung megakaryocytes was found in dengue patients than the control group, presenting a statistically significant difference (5.32 ± 2.69 vs. 2.61 ± 1.97 respectively, p < 0.001). The majority of patients showed bleedingwarning signs (55.88%) and hemorrhage signs at autopsies (91.18%). Regarding thrombotic events, they occurred in 35.29% of fatal dengue cases and 58.33% of thrombotic events were pulmonary. The results also revealed that 38.24% of dengue patients had pulmonary megakaryocytes stained against NS3, confirming the presence of DENV replication in these cells. In summary, it was demonstrated an increase in the number of lung megakaryocytes and the in vivo NS3 expression in lung megakaryocytes from patients with severedengue fever, indicating that DENV can infect these cells, compromising platelet production, therefore contributing to an unfavorable prognosis.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-11-23T14:52:21Z
dc.date.available.fl_str_mv 2023-11-23T14:52:21Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv LOPES, Renata Lima. Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica. 2023. Dissertação (Mestrado em Patologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75046. Acesso em: 23 nov. 2023.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/75046
identifier_str_mv LOPES, Renata Lima. Estudo de megacariócitos e da expressão de NS3 em pulmões de casos de dengue fatal: associação clínico-patológica. 2023. Dissertação (Mestrado em Patologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75046. Acesso em: 23 nov. 2023.
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