Phosphodiesterase inhibitors in the treatment of sepsis and septic shock
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Research, Society and Development |
Texto Completo: | https://rsdjournal.org/index.php/rsd/article/view/12269 |
Resumo: | Sepsis is a prevalent syndrome defined as a life-threatening organ dysfunction caused by a host's unregulated response to an infection, which can manifest itself in several ways. The pathophysiology of the syndrome involves the inflammatory and immunological pathways, and the response of the circulatory system plays a fundamental role in ischemia and organic injury. Phosphodiesterase inhibitors (iPDE) act by increasing the levels of cyclic nucleotides (cAMP and / or cGMP). These agents promote several effects according to their selectivity, among them: vasodilation, increased cardiac output, decreased endothelial permeability, inhibition of pro-inflammatory cytokines, and inhibition of coagulation. In view of this, the hypothesis was raised that iPDE could be beneficial in the treatment of sepsis. Clinical studies that used iPDE agents to treat sepsis show promising results. Animal models have been used to investigate the mechanisms involved in the pathology of sepsis, as well as new therapeutic options. The phosphodiesterase enzyme is classified in 11 families, and the research is focused on non-selective PDE inhibitor drugs, iPDE-3, iPDE-4 and iPDE-5. Two main septic models are used: application of Escherichia coli lipopolysaccharide and ligation and cecal puncture surgery. The drugs are administered intraperitoneally or intravenously before sepsis induction, in different doses. Despite the large number of positive results, the differences found between the septic models show the need for standardization of methods to obtain reliable data that can be used in clinical research. |
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Phosphodiesterase inhibitors in the treatment of sepsis and septic shockInhibidores de la fosfodiesterasa en el tratamiento de la sepsis y el shock sépticoAgentes inibidores da fosfodiesterase no tratamento da sepse e choque séptico Drug TherapyPhosphodiesterase InhibitorsInflammationAnimal experimentation.FarmacoterapiaInibidores de la fodfodiesterasaInflamaciónExperimentación animal.Terapia MedicamentosaInibidores da FosfodiesteraseInflamaçãoExperimentação animal.Sepsis is a prevalent syndrome defined as a life-threatening organ dysfunction caused by a host's unregulated response to an infection, which can manifest itself in several ways. The pathophysiology of the syndrome involves the inflammatory and immunological pathways, and the response of the circulatory system plays a fundamental role in ischemia and organic injury. Phosphodiesterase inhibitors (iPDE) act by increasing the levels of cyclic nucleotides (cAMP and / or cGMP). These agents promote several effects according to their selectivity, among them: vasodilation, increased cardiac output, decreased endothelial permeability, inhibition of pro-inflammatory cytokines, and inhibition of coagulation. In view of this, the hypothesis was raised that iPDE could be beneficial in the treatment of sepsis. Clinical studies that used iPDE agents to treat sepsis show promising results. Animal models have been used to investigate the mechanisms involved in the pathology of sepsis, as well as new therapeutic options. The phosphodiesterase enzyme is classified in 11 families, and the research is focused on non-selective PDE inhibitor drugs, iPDE-3, iPDE-4 and iPDE-5. Two main septic models are used: application of Escherichia coli lipopolysaccharide and ligation and cecal puncture surgery. The drugs are administered intraperitoneally or intravenously before sepsis induction, in different doses. Despite the large number of positive results, the differences found between the septic models show the need for standardization of methods to obtain reliable data that can be used in clinical research.La sepsis es un síndrome prevalente definido como una disfunción orgánica potencialmente mortal causada por la respuesta no regulada de un huésped a una infección, que puede manifestarse de varias formas. La fisiopatología del síndrome involucra las vías inflamatoria e inmunológica, y la respuesta del sistema circulatorio juega un papel fundamental en la isquemia y lesión orgánica. Los fármacos inhibidores de la fosfodiesterasa (iPDE) actúan aumentando los niveles de nucleótidos cíclicos (cAMP y / o cGMP). Estos agentes pueden producir diversos efectos según su selectividad, entre ellos: vasodilatación, aumento del gasto cardíaco, disminución de la permeabilidad endotelial, inhibición de citocinas proinflamatorias e inhibición de la coagulación. En vista de esto, se planteó la hipótesis de que el iPDE podría ser beneficioso en el tratamiento de la sepsis. Los estudios clínicos que utilizaron agentes iPDE para tratar la sepsis muestran resultados prometedores. Se han utilizado modelos animales para investigar los mecanismos implicados en la patología de la sepsis, así como nuevas opciones terapéuticas. La enzima fosfodiesterasa se clasifica en 11 familias y la investigación se centra en fármacos inhibidores de la PDE no selectivos, iPDE-3, iPDE-4 e iPDE-5. Se utilizan dos modelos sépticos principales: aplicación de lipopolisacárido de Escherichia coli y cirugía de ligadura y punción cecal. Los fármacos se administran por vía intraperitoneal o intravenosa antes de la inducción de la sepsis, en diferentes dosis. A pesar de la gran cantidad de resultados positivos, las diferencias encontradas entre los modelos sépticos muestran la necesidad de estandarizar los métodos para obtener datos confiables que puedan ser utilizados en la investigación clínica.A sepse é uma síndrome prevalente definida como uma disfunção orgânica com risco de vida causada por uma resposta desregulada do hospedeiro a uma infecção, podendo manifestar-se de diversas formas. A fisiopatologia da síndrome envolve as vias inflamatória e imunológica, sendo que a resposta do sistema circulatório exerce um papel fundamental na isquemia e lesão orgânica. Os fármacos inibidores da fosfodiesterase (iPDE) agem aumentando os níveis dos nucleotídeos cíclicos (AMPc e/ou GMPc). Esses agentes podem causar vários efeitos de acordo com a sua seletividade, entre eles: vasodilatação, aumento do débito cardíaco, diminuição da permeabilidade endotelial, inibição de citocinas pró-inflamatórias, e inibição da coagulação. Diante disso, foi levantado a hipótese de que os iPDE poderiam ser benéficos no tratamento da sepse. Estudos clínicos que utilizaram agentes iPDE no tratamento da sepse demonstram resultados promissores. Modelos animais têm sido utilizados para a investigação dos mecanismos envolvidos na patologia da sepse, bem como novas opções terapêuticas. A enzima fosfodiesterase é classificada em 11 famílias, sendo que as pesquisas são focadas nos fármacos inibidores não seletivos da PDE, iPDE-3, iPDE-4 e iPDE-5. Dois modelos sépticos principais são utilizados: aplicação de lipopolissácarídeo de Escherichia coli e cirurgia de ligadura e punção cecal. Os medicamentos são administrados de forma intraperitoneal ou intravenosa antes os depois da indução de sepse, em diferentes doses. Apesar do grande número de resultados positivos, as diferenças encontradas entre os modelos sépticos evidenciam a necessidade de padronização de métodos para a obtenção de dados confiáveis que possam ser utilizados na pesquisa clínica. Research, Society and Development2021-01-31info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/1226910.33448/rsd-v10i1.12269Research, Society and Development; Vol. 10 No. 1; e56310112269Research, Society and Development; Vol. 10 Núm. 1; e56310112269Research, Society and Development; v. 10 n. 1; e563101122692525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIporhttps://rsdjournal.org/index.php/rsd/article/view/12269/10867Copyright (c) 2021 Gabrielle Delfrate; Daniel Fernandes; Gilson Cesar Nobre Francohttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessDelfrate, GabrielleFernandes, DanielFranco, Gilson Cesar Nobre2021-02-20T21:19:23Zoai:ojs.pkp.sfu.ca:article/12269Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2024-01-17T09:33:53.587471Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false |
dc.title.none.fl_str_mv |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock Inhibidores de la fosfodiesterasa en el tratamiento de la sepsis y el shock séptico Agentes inibidores da fosfodiesterase no tratamento da sepse e choque séptico |
title |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
spellingShingle |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock Delfrate, Gabrielle Drug Therapy Phosphodiesterase Inhibitors Inflammation Animal experimentation. Farmacoterapia Inibidores de la fodfodiesterasa Inflamación Experimentación animal. Terapia Medicamentosa Inibidores da Fosfodiesterase Inflamação Experimentação animal. |
title_short |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
title_full |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
title_fullStr |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
title_full_unstemmed |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
title_sort |
Phosphodiesterase inhibitors in the treatment of sepsis and septic shock |
author |
Delfrate, Gabrielle |
author_facet |
Delfrate, Gabrielle Fernandes, Daniel Franco, Gilson Cesar Nobre |
author_role |
author |
author2 |
Fernandes, Daniel Franco, Gilson Cesar Nobre |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Delfrate, Gabrielle Fernandes, Daniel Franco, Gilson Cesar Nobre |
dc.subject.por.fl_str_mv |
Drug Therapy Phosphodiesterase Inhibitors Inflammation Animal experimentation. Farmacoterapia Inibidores de la fodfodiesterasa Inflamación Experimentación animal. Terapia Medicamentosa Inibidores da Fosfodiesterase Inflamação Experimentação animal. |
topic |
Drug Therapy Phosphodiesterase Inhibitors Inflammation Animal experimentation. Farmacoterapia Inibidores de la fodfodiesterasa Inflamación Experimentación animal. Terapia Medicamentosa Inibidores da Fosfodiesterase Inflamação Experimentação animal. |
description |
Sepsis is a prevalent syndrome defined as a life-threatening organ dysfunction caused by a host's unregulated response to an infection, which can manifest itself in several ways. The pathophysiology of the syndrome involves the inflammatory and immunological pathways, and the response of the circulatory system plays a fundamental role in ischemia and organic injury. Phosphodiesterase inhibitors (iPDE) act by increasing the levels of cyclic nucleotides (cAMP and / or cGMP). These agents promote several effects according to their selectivity, among them: vasodilation, increased cardiac output, decreased endothelial permeability, inhibition of pro-inflammatory cytokines, and inhibition of coagulation. In view of this, the hypothesis was raised that iPDE could be beneficial in the treatment of sepsis. Clinical studies that used iPDE agents to treat sepsis show promising results. Animal models have been used to investigate the mechanisms involved in the pathology of sepsis, as well as new therapeutic options. The phosphodiesterase enzyme is classified in 11 families, and the research is focused on non-selective PDE inhibitor drugs, iPDE-3, iPDE-4 and iPDE-5. Two main septic models are used: application of Escherichia coli lipopolysaccharide and ligation and cecal puncture surgery. The drugs are administered intraperitoneally or intravenously before sepsis induction, in different doses. Despite the large number of positive results, the differences found between the septic models show the need for standardization of methods to obtain reliable data that can be used in clinical research. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-31 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/12269 10.33448/rsd-v10i1.12269 |
url |
https://rsdjournal.org/index.php/rsd/article/view/12269 |
identifier_str_mv |
10.33448/rsd-v10i1.12269 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/12269/10867 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2021 Gabrielle Delfrate; Daniel Fernandes; Gilson Cesar Nobre Franco https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2021 Gabrielle Delfrate; Daniel Fernandes; Gilson Cesar Nobre Franco https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Research, Society and Development |
publisher.none.fl_str_mv |
Research, Society and Development |
dc.source.none.fl_str_mv |
Research, Society and Development; Vol. 10 No. 1; e56310112269 Research, Society and Development; Vol. 10 Núm. 1; e56310112269 Research, Society and Development; v. 10 n. 1; e56310112269 2525-3409 reponame:Research, Society and Development instname:Universidade Federal de Itajubá (UNIFEI) instacron:UNIFEI |
instname_str |
Universidade Federal de Itajubá (UNIFEI) |
instacron_str |
UNIFEI |
institution |
UNIFEI |
reponame_str |
Research, Society and Development |
collection |
Research, Society and Development |
repository.name.fl_str_mv |
Research, Society and Development - Universidade Federal de Itajubá (UNIFEI) |
repository.mail.fl_str_mv |
rsd.articles@gmail.com |
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1797052783399010304 |