Base de dados : MEDLINE
Pesquisa : D08.811.277.656.350.245.125 [Categoria DeCS]
Referências encontradas : 647 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 65 ir para página                         

  1 / 647 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28552956
[Au] Autor:Zwingerman N; Medina-Rivera A; Kassam I; Wilson MD; Morange PE; Trégouët DA; Gagnon F
[Ad] Endereço:Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
[Ti] Título:Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis.
[So] Source:PLoS One;12(5):e0177768, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. METHODS: A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. RESULTS: A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96-1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71-0.97, p = 0.021) for venous thrombosis. CONCLUSIONS: A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models.
[Mh] Termos MeSH primário: Alanina/genética
Carboxipeptidase B2/genética
Predisposição Genética para Doença
Fatores Sexuais
Treonina/genética
Trombose Venosa/genética
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Isoleucina/genética
Masculino
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
04Y7590D77 (Isoleucine); 2ZD004190S (Threonine); EC 3.4.17.20 (CPB2 protein, human); EC 3.4.17.20 (Carboxypeptidase B2); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177768


  2 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28472123
[Au] Autor:Bridge K; Revill C; Macrae F; Bailey M; Yuldasheva N; Wheatcroft S; Butlin R; Foster R; Scott DJ; Gils A; Ariens R
[Ad] Endereço:Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Research, University of Leeds, Leeds, United Kingdom.
[Ti] Título:Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms.
[So] Source:PLoS One;12(5):e0177117, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. METHODS: Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. RESULTS: Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. CONCLUSIONS: The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression.
[Mh] Termos MeSH primário: Carboxipeptidase B2/antagonistas & inibidores
Modelos Animais de Doenças
Fibrinolisina/metabolismo
[Mh] Termos MeSH secundário: Animais
Aneurisma da Aorta Abdominal/patologia
Apolipoproteínas E/genética
Carboxipeptidase B2/metabolismo
Progressão da Doença
Masculino
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoproteins E); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.17.20 (Cpb2 protein, mouse); EC 3.4.21.7 (Fibrinolysin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177117


  3 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28289017
[Au] Autor:Satoh T; Satoh K; Yaoita N; Kikuchi N; Omura J; Kurosawa R; Numano K; Al-Mamun E; Siddique MA; Sunamura S; Nogi M; Suzuki K; Miyata S; Morser J; Shimokawa H
[Ad] Endereço:From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (T.S., K. Satoh, N.Y., N.K., J.O., R.K., K.N., E.A.-M., M.A.H.S., S.S., M.N., K. Suzuki, S.M., H.S.); and Department of Hematology, Stanford School of Medicine, CA (J.M.).
[Ti] Título:Activated TAFI Promotes the Development of Chronic Thromboembolic Pulmonary Hypertension: A Possible Novel Therapeutic Target.
[So] Source:Circ Res;120(8):1246-1262, 2017 Apr 14.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Pulmonary hypertension is a fatal disease; however, its pathogenesis still remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) is synthesized by the liver and inhibits fibrinolysis. Plasma TAFI levels are significantly increased in chronic thromboembolic pulmonary hypertension (CTEPH) patients. OBJECTIVE: To determine the role of activated TAFI (TAFIa) in the development of CTEPH. METHODS AND RESULTS: Immunostaining showed that TAFI and its binding partner thrombomodulin (TM) were highly expressed in the pulmonary arteries (PAs) and thrombus in patients with CTEPH. Moreover, plasma levels of TAFIa were increased 10-fold in CTEPH patients compared with controls. In mice, chronic hypoxia caused a 25-fold increase in plasma levels of TAFIa with increased plasma levels of thrombin and TM, which led to thrombus formation in PA, vascular remodeling, and pulmonary hypertension. Consistently, plasma clot lysis time was positively correlated with plasma TAFIa levels in mice. Additionally, overexpression of TAFIa caused organized thrombus with multiple obstruction of PA flow and reduced survival rate under hypoxia in mice. Bone marrow transplantation showed that circulating plasma TAFI from the liver, not in the bone marrow, was activated locally in PA endothelial cells through interactions with thrombin and TM. Mechanistic experiments demonstrated that TAFIa increased PA endothelial permeability, smooth muscle cell proliferation, and monocyte/macrophage activation. Importantly, TAFIa inhibitor and peroxisome proliferator-activated receptor-α agonists significantly reduced TAFIa and ameliorated animal models of pulmonary hypertension in mice and rats. CONCLUSIONS: These results indicate that TAFIa could be a novel biomarker and realistic therapeutic target of CTEPH.
[Mh] Termos MeSH primário: Pressão Arterial
Carboxipeptidase B2/metabolismo
Hipertensão Pulmonar/etiologia
Fígado/metabolismo
Artéria Pulmonar/metabolismo
Tromboembolia/complicações
[Mh] Termos MeSH secundário: Adulto
Animais
Permeabilidade Capilar
Carboxipeptidase B2/deficiência
Carboxipeptidase B2/genética
Estudos de Casos e Controles
Proliferação Celular
Doença Crônica
Modelos Animais de Doenças
Feminino
Células Hep G2
Seres Humanos
Hipertensão Pulmonar/metabolismo
Hipertensão Pulmonar/fisiopatologia
Hipertensão Pulmonar/prevenção & controle
Hipóxia/complicações
Fígado/efeitos dos fármacos
Ativação de Macrófagos
Masculino
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Knockout
Meia-Idade
Músculo Liso Vascular/metabolismo
Músculo Liso Vascular/patologia
Músculo Liso Vascular/fisiopatologia
Miócitos de Músculo Liso/metabolismo
Miócitos de Músculo Liso/patologia
PPAR alfa/agonistas
PPAR alfa/metabolismo
Artéria Pulmonar/patologia
Artéria Pulmonar/fisiopatologia
Pirimidinas/farmacologia
Ratos Sprague-Dawley
Transdução de Sinais
Trombina/metabolismo
Tromboembolia/metabolismo
Tromboembolia/fisiopatologia
Tromboembolia/prevenção & controle
Trombomodulina/metabolismo
Transfecção
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PPAR alpha); 0 (Pyrimidines); 0 (THBD protein, human); 0 (Thrombomodulin); 86C4MRT55A (pirinixic acid); EC 3.4.17.20 (CPB2 protein, human); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.17.20 (Cpb2 protein, mouse); EC 3.4.17.20 (Cpb2 protein, rat); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.310640


  4 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28219843
[Au] Autor:Pepler L; Wu C; Dwivedi DJ; Wu C; Kim PY; Liaw PC
[Ad] Endereço:Department of Medical Sciences at McMaster University, Hamilton, Ontario L8L 0A6, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario L8L 0A6, Canada.
[Ti] Título:The impact of the endothelial protein C receptor on thrombin generation and clot lysis.
[So] Source:Thromb Res;152:30-37, 2017 Apr.
[Is] ISSN:1879-2472
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: When thrombin is bound to thrombomodulin (TM), it becomes a potent activator of protein C (PC) and thrombin-activable fibrinolysis inhibitor (TAFI). Activation of PC is enhanced when PC is bound to the endothelial protein C receptor (EPCR). Activated protein C (APC) inhibits thrombin generation while activated TAFI (TAFIa) attenuates fibrinolysis. To determine the impact of diminished EPCR function on thrombin generation and fibrinolysis we generated cells that expressed TM and a variant of EPCR (R96C) that does not bind PC. METHODS: To determine the impact of EPCR on the generation of APC and TAFIa and how this affects thrombin generation and fibrinolysis we performed thrombin generation and clot lysis assays in the presence of cells expressing wild-type TM and EPCR (WT cells) or wild-type TM and the R96C variant of EPCR (R96C cells). RESULTS: In the presence of R96C cells, thrombin generation in normal plasma is increased, as a result of impaired PC activation when compared to WT cells. In addition, clot lysis is delayed in normal plasma in the presence of R96C cells, despite no increase in TAFI activation. In PC deficient plasma, clot lysis is delayed in the presence of WT and R96C cells as a result of increased TAFI activation. CONCLUSIONS: We demonstrate that impaired EPCR function can be detected by thrombin generation and clot lysis assays on cells expressing TM and EPCR. We also demonstrated that deficiency in EPCR has procoagulant effects that lead to a delay in clot lysis.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Fibrinólise
Receptores de Superfície Celular/metabolismo
Trombina/metabolismo
[Mh] Termos MeSH secundário: Coagulação Sanguínea
Carboxipeptidase B2/metabolismo
Linhagem Celular
Receptor de Proteína C Endotelial
Ativação Enzimática
Tempo de Lise do Coágulo de Fibrina
Células HEK293
Seres Humanos
Proteína C/metabolismo
Trombomodulina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Endothelial Protein C Receptor); 0 (PROCR protein, human); 0 (Protein C); 0 (Receptors, Cell Surface); 0 (Thrombomodulin); EC 3.4.17.20 (CPB2 protein, human); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE


  5 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28124276
[Au] Autor:Bazzi ZA; Balun J; Cavallo-Medved D; Porter LA; Boffa MB
[Ad] Endereço:Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.
[Ti] Título:Activated thrombin-activatable fibrinolysis inhibitor attenuates the angiogenic potential of endothelial cells: potential relevance to the breast tumour microenvironment.
[So] Source:Clin Exp Metastasis;34(2):155-169, 2017 Feb.
[Is] ISSN:1573-7276
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Thrombin-activatable fibrinolysis inhibitor (TAFI) is a basic carboxypeptidase zymogen present in blood plasma. Proteolytic activation of TAFI by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin, or plasmin results in an enzyme (TAFIa) that removes carboxyl-terminal lysine residues from protein and peptide substrates, including cell-surface plasminogen receptors. TAFIa is therefore capable of inhibiting plasminogen activation in the pericellular milieu. Since plasminogen activation has been linked to angiogenesis, TAFIa could therefore have anti-angiogenic properties, and indeed TAFIa has been shown to inhibit endothelial tube formation in a fibrin matrix. In this study, the TAFI pathway was manipulated by providing exogenous TAFI or TAFIa or by adding a potent and specific inhibitor of TAFIa. We found that TAFIa elicited a series of anti-angiogenic responses by endothelial cells, including decreased endothelial cell proliferation, cell invasion, cell migration, tube formation, and collagen degradation. Moreover, TAFIa decreased tube formation and proteolysis in endothelial cell culture grown alone and in co-culture with breast cancer cell lines. In accordance with these findings, inhibition of TAFIa increased secretion of matrix metalloprotease proenzymes by endothelial and breast cancer cells. Finally, treatment of endothelial cells with TAFIa significantly inhibited plasminogen activation. Taken together our results suggest a novel role for TAFI in inhibiting tumour angiogenic behaviors in breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Carboxipeptidase B2/fisiologia
Células Endoteliais/efeitos dos fármacos
Neovascularização Patológica/tratamento farmacológico
[Mh] Termos MeSH secundário: Carboxipeptidase B2/antagonistas & inibidores
Carboxipeptidase B2/farmacologia
Divisão Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Técnicas de Cocultura
Colágeno Tipo IV/metabolismo
Ensaios de Seleção de Medicamentos Antitumorais
Ativação Enzimática/efeitos dos fármacos
Precursores Enzimáticos/farmacologia
Células HEK293
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Metaloproteinase 2 da Matriz/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Plasminogênio/antagonistas & inibidores
Proteínas Recombinantes/metabolismo
Proteínas Recombinantes/farmacologia
Transdução de Sinais/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type IV); 0 (Enzyme Precursors); 0 (Recombinant Proteins); 0 (Vascular Endothelial Growth Factor A); 9001-91-6 (Plasminogen); EC 3.4.17.20 (CPB2 protein, human); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.24.24 (MMP2 protein, human); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (MMP9 protein, human); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE
[do] DOI:10.1007/s10585-017-9837-y


  6 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27749053
[Au] Autor:Halland N; Czech J; Czechtizky W; Evers A; Follmann M; Kohlmann M; Schreuder HA; Kallus C
[Ad] Endereço:Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
[Ti] Título:Sulfamide as Zinc Binding Motif in Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa).
[So] Source:J Med Chem;59(20):9567-9573, 2016 Oct 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Previously disclosed TAFIa inhibitors having a urea zinc-binding motif were used as the starting point for the development of a novel class of highly potent inhibitors having a sulfamide zinc-binding motif. High-resolution X-ray cocrystal structures were used to optimize the structures and reveal a highly unusual sulfamide configuration. A selected sulfamide was profiled in vitro and in vivo and displayed a promising ADMET profile.
[Mh] Termos MeSH primário: Carboxipeptidase B2/antagonistas & inibidores
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Bibliotecas de Moléculas Pequenas/química
Bibliotecas de Moléculas Pequenas/farmacologia
Sulfonamidas/farmacologia
Zinco/química
[Mh] Termos MeSH secundário: Animais
Carboxipeptidase B2/metabolismo
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Seres Humanos
Camundongos
Microssomos/química
Microssomos/metabolismo
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteases/síntese química
Ratos
Bibliotecas de Moléculas Pequenas/síntese química
Relação Estrutura-Atividade
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protease Inhibitors); 0 (Small Molecule Libraries); 0 (Sulfonamides); EC 3.4.17.20 (Carboxypeptidase B2); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE


  7 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27693845
[Au] Autor:Tawara S; Sakai T; Matsuzaki O
[Ad] Endereço:Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan. Electronic address: tawara.sc@om.asahi-kasei.co.jp.
[Ti] Título:Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.
[So] Source:Thromb Res;147:72-79, 2016 Nov.
[Is] ISSN:1879-2472
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. METHODS: CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. RESULTS: CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. CONCLUSIONS: TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Carboxipeptidase B2/imunologia
Fibrinolíticos/farmacologia
Trombina/antagonistas & inibidores
[Mh] Termos MeSH secundário: Ensaios de Migração de Leucócitos
Inibição de Migração Celular/efeitos dos fármacos
Complemento C5a/imunologia
Ativação Enzimática/efeitos dos fármacos
Tempo de Lise do Coágulo de Fibrina
Seres Humanos
Neutrófilos/efeitos dos fármacos
Neutrófilos/imunologia
Proteínas Recombinantes/farmacologia
Trombina/imunologia
Trombomodulina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ART123); 0 (Anti-Inflammatory Agents); 0 (Fibrinolytic Agents); 0 (Recombinant Proteins); 0 (Thrombomodulin); 80295-54-1 (Complement C5a); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE


  8 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27470988
[Au] Autor:Denorme F; Wyseure T; Peeters M; Vandeputte N; Gils A; Deckmyn H; Vanhoorelbeke K; Declerck PJ; De Meyer SF
[Ad] Endereço:From the Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Belgium (F.D., N.V., H.D., K.V., S.F.D.M.); and Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium (T.W., M.P., A.G., P.J.D.).
[Ti] Título:Inhibition of Thrombin-Activatable Fibrinolysis Inhibitor and Plasminogen Activator Inhibitor-1 Reduces Ischemic Brain Damage in Mice.
[So] Source:Stroke;47(9):2419-22, 2016 Sep.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Cerebral ischemia and reperfusion is associated with activation of the coagulation cascade and fibrin deposition in cerebral microvessels. Both thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) attenuate fibrinolysis and are therefore attractive targets for the treatment of ischemic stroke. METHODS: TAFI and PAI-1 were inhibited by monoclonal antibodies in a mouse model of transient middle cerebral artery occlusion. Twenty-four hours after stroke, mice were neurologically scored, cerebral thrombotic burden was assessed, and brain infarct sizes were calculated. RESULTS: Inhibition of TAFI or PAI-1 significantly decreased cerebral infarct sizes by 50% 24 hours after stroke. This reduction in cerebral damage was associated with a significant decrease in fibrin(ogen) deposition in the ischemic brain. Concurrently, functional recovery of the animals was improved. Interestingly, combined targeting of TAFI and PAI-1 using low, and by themselves inactive, doses of antibodies improved cerebral blood flow and reduced cerebral fibrin(ogen) deposition and infarct sizes by 50%. When dual treatment was delayed to 1 hour after the start of reperfusion, it still reduced brain injury; however, this was not statistically significant. CONCLUSIONS: Targeting of PAI-1 and TAFI is protective in an ischemic stroke model by attenuating fibrin(ogen) deposition, thereby improving reperfusion. Combined inhibition has a co-operative effect that could become useful in ischemic stroke therapy.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico
Isquemia Encefálica/tratamento farmacológico
Encéfalo/efeitos dos fármacos
Carboxipeptidase B2/imunologia
Inibidor 1 de Ativador de Plasminogênio/imunologia
Acidente Vascular Cerebral/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/farmacologia
Modelos Animais de Doenças
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Plasminogen Activator Inhibitor 1); EC 3.4.17.20 (Carboxypeptidase B2); EC 3.4.17.20 (Cpb2 protein, mouse)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160730
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.116.014091


  9 / 647 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27432089
[Au] Autor:Beyazit Y; Sayilir A; Tanoglu A; Kekilli M; Kocak E; Ekiz F; Tas A
[Ad] Endereço:Department of Gastroenterology, Canakkale State Hospital, Turkey.
[Ti] Título:Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis.
[So] Source:Intern Med;55(14):1831-6, 2016.
[Is] ISSN:1349-7235
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Objective Patients with ulcerative colitis (UC) are at an increased risk for thromboembolic events, particularly in patients with extensive and active disease. To date, a few studies have been published on the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in UC. However, there are no reports in the literature investigating the effect of UC treatment on plasma TAFI levels. Methods The plasma TAFI antigen levels were quantitatively determined using ELISA kits for 20 UC patients at activation and remission, along with 17 healthy controls. The association between the TAFI levels and inflammatory markers was assessed to determine UC activation. To predict and determine the activation of UC, the Truelove-Witts index and the endoscopic activation index (EAI) were used for each subject. Results The plasma TAFI levels were higher in UC patients at activation of the disease compared with the remission state and in healthy controls. Spearman's correlation analyses revealed that the WBC (r: 0.586, p<0.001), hsCRP (r: 0.593, p<0.001) and EAI (r: 0.721, p<0.001) were significantly correlated with the TAFI levels. The overall accuracy of TAFI in determining UC activation was 82.5% with a sensitivity, specificity, NPV and PPV of 80%, 85%, 81% and 84.2%, respectively (cut-off value: 156.2% and AUC: 0.879). Conclusion The present study demonstrates that the TAFI levels are elevated in the active state of UC. The assessment of TAFI levels in patients with UC in conjunction with other markers of inflammation may provide additional information for estimating UC activation and severity.
[Mh] Termos MeSH primário: Carboxipeptidase B2/sangue
Colite Ulcerativa/sangue
Mediadores da Inflamação/metabolismo
Inflamação/sangue
[Mh] Termos MeSH secundário: Adulto
Biomarcadores
Carboxipeptidase B2/imunologia
Colite Ulcerativa/metabolismo
Ensaio de Imunoadsorção Enzimática
Feminino
Seres Humanos
Inflamação/metabolismo
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Inflammation Mediators); EC 3.4.17.20 (Carboxypeptidase B2)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160720
[St] Status:MEDLINE
[do] DOI:10.2169/internalmedicine.55.6473


  10 / 647 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo SciELO Brasil
[PMID]:27410412
[Au] Autor:Nedel WL; Rodrigues Filho EM; Pasqualotto AC
[Ad] Endereço:Programa de Pós-Graduação em Hepatologia, Universidade Federal de Ciências da Saúde, Porto Alegre, RS, Brazil.
[Ti] Título:Thrombin activatable fibrinolysis inhibitor as a bleeding predictor in liver transplantation: a pilot observational study.
[Ti] Título:Thrombin activatable fibrinolysis inhibitor como preditor de sangramento no transplante hepático: estudo piloto observacional..
[So] Source:Rev Bras Ter Intensiva;28(2):161-6, 2016 Jun.
[Is] ISSN:1982-4335
[Cp] País de publicação:Brazil
[La] Idioma:eng; por
[Ab] Resumo:OBJECTIVE: To correlate the levels of thrombin activatable fibrinolysis inhibitor in the immediate postoperative period and at 24 hours postoperatively with the volume of intraoperative bleeding. METHODS: Twenty-one patients allocated immediately before (elective or emergency) liver transplantation were analyzed. Blood samples were collected for thrombin activatable fibrinolysis inhibitor analysis at three different time points: immediately before liver transplantation (preoperative thrombin activatable fibrinolysis inhibitor), immediately after the surgical procedure (immediate postoperative thrombin activatable fibrinolysis inhibitor), and 24 hours after surgery (thrombin activatable fibrinolysis inhibitor 24 hours after surgery). The primary outcome of the study was to correlate the preoperative and immediate postoperative levels of thrombin activatable fibrinolysis inhibitor with intraoperative blood loss. RESULTS: There was a correlation between the preoperative thrombin activatable fibrinolysis inhibitor levels and bleeding volume (ρ = -0.469; p = 0.05) but no correlation between the immediate postoperative thrombin activatable fibrinolysis inhibitor and bleeding volume (ρ = -0.062; p = 0.79). No variable included in the linear regression analysis (prehemoglobin, prefibrinogen and preoperative thrombin activatable fibrinolysis inhibitor) was a bleeding predictor. There was a similar trend in the variation between the levels of thrombin activatable fibrinolysis inhibitor at the three different time points and fibrinogen levels. Patients who died within 6 months (14.3%) showed decreased preoperative and immediate postoperative levels of thrombin activatable fibrinolysis compared with survivors (preoperative: 1.3 ± 0.15 versus 2.55 ± 0.53, p = 0.06; immediate postoperative: 1.2 ± 0.15 versus 2.5 ± 0.42, p = 0.007). CONCLUSION: There was a moderate correlation between preoperative thrombin activatable fibrinolysis inhibitor and intraoperative bleeding in liver transplantation patients, although the predictive role of this variable independent of other variables remains uncertain. Preoperative and immediate postoperative thrombin activatable fibrinolysis inhibitor levels may have a role in the survival prognosis of this population; however, this possibility requires confirmation in further studies with larger sample sizes.
[Mh] Termos MeSH primário: Perda Sanguínea Cirúrgica
Carboxipeptidase B2/metabolismo
Transplante de Fígado/métodos
[Mh] Termos MeSH secundário: Idoso
Feminino
Fibrinogênio/metabolismo
Seres Humanos
Modelos Lineares
Transplante de Fígado/mortalidade
Masculino
Meia-Idade
Projetos Piloto
Período Pós-Operatório
Período Pré-Operatório
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
9001-32-5 (Fibrinogen); EC 3.4.17.20 (Carboxypeptidase B2)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170322
[Lr] Data última revisão:
170322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160714
[St] Status:MEDLINE



página 1 de 65 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde