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[PMID]:27774726
[Au] Autor:Jonsson PI; Letertre L; Juliusson SJ; Gudmundsdottir BR; Francis CW; Onundarson PT
[Ad] Endereço:Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
[Ti] Título:During warfarin induction, the Fiix-prothrombin time reflects the anticoagulation level better than the standard prothrombin time.
[So] Source:J Thromb Haemost;15(1):131-139, 2017 01.
[Is] ISSN:1538-7836
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Essentials Fiix-prothrombin time (PT) monitoring of warfarin measuring factor (F) II and X, is effective. Plasma obtained during warfarin induction and stable phase in Fiix-trial was assayed. Fiix-PT stabilized anticoagulation earlier than monitoring with traditional PT-INR. FVII had little effect on thrombin generation that was mainly determined by FII and FX. SUMMARY: Background The prothrombin time (PT) is equally prolonged by reduction of each of the vitamin K-dependent (VKD) factors (F) II, VII and X. The Fiix-PT is only affected by FII and FX, the main contributors to thrombin generation (TG). Objective To test the hypothesis that variability in warfarin anticoagulation is reduced early during monitoring with the normalized PT-ratio calculated from Fiix-PT (Fiix-International Normalized Ratio [INR]) compared with traditional PT-INR monitoring. Also, that because of its insensitivity to FVII, Fiix-PT more accurately reflects TG when Fiix-INR and PT-INR are discrepant. Methods Samples from Fiix-trial participants monitored with either Fiix-PT or PT were used. VKD coagulation factors and TG were measured in samples from 40 patients during stable anticoagulation and in serial samples obtained from 26 patients during warfarin induction. TG was assessed in relation to selective reduction in single VKD factors. Results During Fiix-warfarin induction full anticoagulation measured as FII or FX activity was achieved at a similar rate to that with PT-warfarin but subsequently stabilized better. Fiix-INR but not PT-INR mirrored total TG during initiation. During induction, FII (R = 0.66) and FX (R = 0.52) correlated better with TG and with a steeper slope than did FIX (R = 0.37) and in particular FVII (R = 0.21). In vitro, FII and FX were the main determinants of TG at concentrations observed during VKA anticoagulation, whereas FVII and FIX had little influence. Conclusions Fiix-PT monitoring reduces anticoagulation variability, suggesting that monitoring FVII has a limited role during VKA management. TG is better reflected by Fiix-PT.
[Mh] Termos MeSH primário: Anticoagulantes/uso terapêutico
Fator X/química
Protrombina/química
Varfarina/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Coagulação Sanguínea/efeitos dos fármacos
Fatores de Coagulação Sanguínea/uso terapêutico
Testes de Coagulação Sanguínea/métodos
Método Duplo-Cego
Monitoramento de Medicamentos
Feminino
Hemostáticos/uso terapêutico
Seres Humanos
Coeficiente Internacional Normatizado
Masculino
Meia-Idade
Tempo de Protrombina
Trombina/química
Vitamina K/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Blood Coagulation Factors); 0 (Hemostatics); 12001-79-5 (Vitamin K); 5Q7ZVV76EI (Warfarin); 9001-26-7 (Prothrombin); 9001-29-0 (Factor X); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1111/jth.13549


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[PMID]:29183533
[Au] Autor:Iida H; Aihara T; Ikuta S; Yamanaka N
[Ti] Título:Predictive Factors for Treatment Failure after Peritoneovenous Shunt for Hepatic Ascites.
[So] Source:Am Surg;83(11):1289-1293, 2017 Nov 01.
[Is] ISSN:1555-9823
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peritoneovenous shunt (PVS) is used to treat refractory ascites. Here, we identify predictive factors for inhospital death after PVS placement. Thirty-five patients with refractory ascites related to liver cirrhosis and/or hepatocellular carcinoma (HCC) who underwent PVS placement between February 2005 and February 2013 were included in the study. Group A comprised 13 patients for whom the PVS placement outcome was inhospital death. Group B comprised 22 patients who were discharged after PVS placement without complications. Patient background and laboratory data were analyzed to identify risk factors for inhospital death. HCC prevalence in Groups A and B was 92 and 55 per cent, respectively (P = 0.02) and that of portal venous tumor thrombus (PVTT) was 54 and 9 per cent, respectively (P = 0.003). The mean des-γ-carboxy prothrombin (DCP) level in both groups was 15,553 ± 49,330 and 787 ± 2600 mAU/mL, respectively (P = 0.009). Multivariate analysis revealed that the presence of PVTT was the only independent predictor of inhospital death (P = 0.007). The presence of PVTT, HCC, and elevated des-γ-carboxy prothrombin levels are predictors of inhospital death after PVS placement. Therefore, PVS should not be used to treat refractory ascites in patients with these predictors, particularly with PVTT.
[Mh] Termos MeSH primário: Ascite/cirurgia
Carcinoma Hepatocelular/cirurgia
Cirrose Hepática/cirurgia
Neoplasias Hepáticas/cirurgia
Derivação Peritoneovenosa/mortalidade
[Mh] Termos MeSH secundário: Idoso
Ascite/mortalidade
Biomarcadores/metabolismo
Carcinoma Hepatocelular/mortalidade
Feminino
Mortalidade Hospitalar
Seres Humanos
Cirrose Hepática/mortalidade
Neoplasias Hepáticas/mortalidade
Masculino
Células Neoplásicas Circulantes
Precursores de Proteínas/metabolismo
Protrombina/metabolismo
Estudos Retrospectivos
Fatores de Risco
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Protein Precursors); 53230-14-1 (acarboxyprothrombin); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171204
[Lr] Data última revisão:
171204
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE


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[PMID]:29054763
[Au] Autor:El-Fattah AAA; Sadik NAH; Sedrak H; Battah A; Nabil M
[Ad] Endereço:Biochemistry department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
[Ti] Título:Association of genetic variants of hemostatic genes with myocardial infarction in Egyptian patients.
[So] Source:Gene;641:212-219, 2018 Jan 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Hemostatic genes polymorphisms are well known to be associated with venous thrombosis, but their association with arterial thrombosis especially myocardial infarction (MI) remains to be clarified. We investigated the role of three hemostatic gene polymorphisms, prothrombin G20210A, factor XIII (FXIII) Val34Leu (G/T), and fibrinogen-ß-455G/A and their coexistence in Egyptian patients with MI. The possible correlation of these polymorphisms with plasma fibrinogen level was also evaluated. The study included 120 patients with MI and 60 healthy volunteers. Gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. Plasma fibrinogen level was determined by ELISA. Our study showed an increased risk of MI with fibrinogen ß-455G/A heterozygosity as well as FXIII Val34Leu homo and heterozygosity. In addition, the FXIII T allele (Leu34) and fibrinogen ß-455A allele were significantly associated with MI. Conversely, the prevalence of prothrombin mutation did not differ between patients with MI and controls. Combined carriers of FXIII Leu34 and fibrinogen-ß455A alleles were at higher risk of MI, whereas combined FXIII Val34Leu and prothrombin 20210A polymorphisms did not show increased risk for MI compared with controls. Plasma fibrinogen levels were significantly higher in patients with MI than controls. In MI patients, plasma fibrinogen levels were significantly higher in those with FXIII GT/TT or fibrinogen ß-455 GA, while were significantly lower in those with prothrombin 20210 GA compared with patients with wild type genotypes. In conclusion, our results suggest a possible thrombotic predisposition of FXIII Val34Leu, fibrinogen ß-455G/A polymorphisms and their coexistence for MI. These polymorphisms may add complexity to disease pathology by increasing plasma fibrinogen level. Extended studies are needed to confirm our results; nevertheless, these data may be implicated in genetic counseling and screening of high-risk individuals.
[Mh] Termos MeSH primário: Fator XIII/genética
Fibrinogênio/genética
Hemostasia/genética
Infarto do Miocárdio/genética
Polimorfismo Genético/genética
Protrombina/genética
[Mh] Termos MeSH secundário: Alelos
Estudos de Casos e Controles
Egito
Feminino
Genótipo
Heterozigoto
Seres Humanos
Masculino
Meia-Idade
Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9001-26-7 (Prothrombin); 9001-32-5 (Fibrinogen); 9013-56-3 (Factor XIII)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171022
[St] Status:MEDLINE


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[PMID]:29034775
[Au] Autor:Hong YM; Cho M; Yoon KT; Chu CW; Yang KH; Park YM; Rhu JH
[Ad] Endereço:1 Department of Internal Medicine, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
[Ti] Título:Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma.
[So] Source:Tumour Biol;39(10):1010428317720863, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Early recurrence is common after curative hepatectomy for hepatocellular carcinoma and is associated with poor prognosis. This study aimed to identify risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Overall, 63 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. Patients were divided into the early recurrence group, who developed recurrence within 12 months after hepatectomy (n = 10), and the non-early recurrence group (n = 53). Clinicopathological factors of early recurrence were retrospectively analyzed. Among the 63 patients, 10 (15.9%) patients experienced early recurrence. Univariate analysis showed tumor necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be associated with early recurrence. By multivariate analysis, there were significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p = 0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively. Patients with a high preoperative PIVKA-II level and extent of tumor necrosis, which are independent risk factors for early recurrence, should be actively treated and monitored closely after hepatectomy.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/cirurgia
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/cirurgia
Recidiva Local de Neoplasia/etiologia
Recidiva Local de Neoplasia/patologia
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Carcinoma Hepatocelular/metabolismo
Feminino
Hepatectomia/métodos
Seres Humanos
Neoplasias Hepáticas/metabolismo
Masculino
Microvasos/metabolismo
Microvasos/patologia
Meia-Idade
Análise Multivariada
Necrose/metabolismo
Necrose/patologia
Invasividade Neoplásica/patologia
Recidiva Local de Neoplasia/metabolismo
Precursores de Proteínas/metabolismo
Protrombina/metabolismo
Estudos Retrospectivos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Protein Precursors); 53230-14-1 (acarboxyprothrombin); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317720863


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[PMID]:28857856
[Au] Autor:Schöchl H; Grottke O; Sutor K; Dony K; Schreiber M; Ranucci M; Collins PW
[Ad] Endereço:From the *Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria; †Department of Anaesthesiology and Intensive Care, AUVA Trauma Centre, Salzburg, Austria; ‡Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany; §Meridian HealthComms Ltd, Plumley, Cheshire, United Kingdom; ‖Parker Design Consultants Ltd, Lostock Gralam, Cheshire, United Kingdom; ¶Trauma, Critical Care and Acute Care Surgery Division, Oregon Health and Science University, Portland, Oregon; #Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy; and **School of Medicine, Cardiff University and University Hospital of Wales, Cardiff, United Kingdom.
[Ti] Título:Theoretical Modeling of Coagulation Management With Therapeutic Plasma or Prothrombin Complex Concentrate.
[So] Source:Anesth Analg;125(5):1471-1474, 2017 Nov.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prothrombin complex concentrates (PCCs) have been associated with a possible risk of thromboembolic complications, potentially attributable to an increased ratio of the plasma concentration of factor II (FII) to antithrombin (AT). We developed a mathematical model to examine the relationship between amounts of PCC or therapeutic plasma administered, and plasma levels of FII and AT. The model showed that PCC produces substantial increases in plasma levels of FII but only small changes in AT, increasing the FII:AT ratio. Therapeutic plasma was shown to have only modest effects on levels of FII or AT, unless high doses are used.
[Mh] Termos MeSH primário: Fatores de Coagulação Sanguínea/uso terapêutico
Coagulação Sanguínea/efeitos dos fármacos
Hemorragia/prevenção & controle
Hemostáticos/uso terapêutico
Modelos Biológicos
[Mh] Termos MeSH secundário: Antitrombinas/metabolismo
Fatores de Coagulação Sanguínea/efeitos adversos
Hemorragia/sangue
Hemostáticos/efeitos adversos
Seres Humanos
Soluções Isotônicas/uso terapêutico
Substitutos do Plasma/uso terapêutico
Volume Plasmático
Protrombina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antithrombins); 0 (Blood Coagulation Factors); 0 (Hemostatics); 0 (Isotonic Solutions); 0 (Plasma Substitutes); 0 (crystalloid solutions); 37224-63-8 (prothrombin complex concentrates); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000002410


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[PMID]:28801460
[Au] Autor:Muehl EM; Gajsiewicz JM; Medfisch SM; Wiersma ZSB; Morrissey JH; Bailey RC
[Ad] Endereço:From the Departments of Chemistry and.
[Ti] Título:Multiplexed silicon photonic sensor arrays enable facile characterization of coagulation protein binding to nanodiscs with variable lipid content.
[So] Source:J Biol Chem;292(39):16249-16256, 2017 Sep 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interactions of soluble proteins with the cell membrane are critical within the blood coagulation cascade. Of particular interest are the interactions of γ-carboxyglutamic acid-rich domain-containing clotting proteins with lipids. Variability among conventional analytical methods presents challenges for comparing clotting protein-lipid interactions. Most previous studies have investigated only a single clotting protein and lipid composition and have yielded widely different binding constants. Herein, we demonstrate that a combination of lipid bilayer nanodiscs and a multiplexed silicon photonic analysis technology enables high-throughput probing of many protein-lipid interactions among blood-clotting proteins. This approach allowed direct comparison of the binding constants of prothrombin, factor X, activated factor VII, and activated protein C to seven different binary lipid compositions. In a single experiment, the binding constants of one protein interacting with all lipid compositions were simultaneously determined. A simple surface regeneration then facilitated similar binding measurements for three other coagulation proteins. As expected, our results indicated that all proteins exhibit tighter binding (lower ) as the proportion of anionic lipid increases. Interestingly, at high proportions of phosphatidylserine, the values of all four proteins began to converge. We also found that although values for all four proteins followed trends similar to those observed for the values, the variation among the proteins was much lower, indicating that much of the variation came from the kinetic binding ( ) of the proteins. These findings indicate that the combination of silicon photonic microring resonator arrays and nanodiscs enables rapid interrogation of biomolecular binding interactions at model cell membrane interfaces.
[Mh] Termos MeSH primário: Fator VIIa/metabolismo
Fator X/metabolismo
Ácidos Fosfatídicos/metabolismo
Fosfatidilcolinas/metabolismo
Fosfatidilserinas/metabolismo
Proteína C/metabolismo
Protrombina/metabolismo
[Mh] Termos MeSH secundário: Fator VIIa/química
Fator VIIa/genética
Fator X/química
Ensaios de Triagem em Larga Escala
Seres Humanos
Cinética
Bicamadas Lipídicas/química
Bicamadas Lipídicas/metabolismo
Nanoestruturas/química
Fenômenos Ópticos
Ácidos Fosfatídicos/química
Fosfatidilcolinas/química
Fosfatidilserinas/química
Análise Serial de Proteínas
Proteína C/química
Protrombina/química
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Silício/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-palmitoyl-2-oleoyl-glycero-3-phosphatidic acid); 0 (Lipid Bilayers); 0 (Phosphatidic Acids); 0 (Phosphatidylcholines); 0 (Phosphatidylserines); 0 (Protein C); 0 (Recombinant Proteins); 40290-44-6 (1-palmitoyl-2-oleoylglycero-3-phosphoserine); 9001-26-7 (Prothrombin); 9001-29-0 (Factor X); EC 3.4.21.21 (Factor VIIa); TE895536Y5 (1-palmitoyl-2-oleoylphosphatidylcholine); Z4152N8IUI (Silicon)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.800938


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[PMID]:28684417
[Au] Autor:Pontarollo G; Acquasaliente L; Peterle D; Frasson R; Artusi I; De Filippis V
[Ad] Endereço:From the Department of Pharmaceutical and Pharmacological Sciences, University of Padua, via Marzolo 5, Padua 35131, Italy.
[Ti] Título:Non-canonical proteolytic activation of human prothrombin by subtilisin from may shift the procoagulant-anticoagulant equilibrium toward thrombosis.
[So] Source:J Biol Chem;292(37):15161-15179, 2017 Sep 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active α-thrombin (αT). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive precursor prethrombin-2 (Pre2), which is further attacked at Arg-320-Ile-321 to yield mature αT. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation. This knowledge gap is particularly concerning, as bacterial infections are frequently complicated by severe coagulopathies. Here, we show that addition of subtilisin (50 nm to 2 µm), a serine protease secreted by the non-pathogenic bacterium , induces plasma clotting by proteolytically converting ProT into active σPre2, a nicked Pre2 derivative with a single cleaved Ala-470-Asn-471 bond. Notably, we found that this non-canonical cleavage at Ala-470-Asn-471 is instrumental for the onset of catalysis in σPre2, which was, however, reduced about 100-200-fold compared with αT. Of note, σPre2 could generate fibrin clots from fibrinogen, either in solution or in blood plasma, and could aggregate human platelets, either isolated or in whole blood. Our findings demonstrate that alternative cleavage of ProT by proteases, even by those secreted by non-virulent bacteria such as , can shift the delicate procoagulant-anticoagulant equilibrium toward thrombosis.
[Mh] Termos MeSH primário: Bacillus subtilis/enzimologia
Proteínas de Bactérias/metabolismo
Coagulação Sanguínea
Modelos Moleculares
Agregação Plaquetária
Protrombina/agonistas
Subtilisina/metabolismo
[Mh] Termos MeSH secundário: Adulto
Proteínas de Bactérias/antagonistas & inibidores
Coagulação Sanguínea/efeitos dos fármacos
Domínio Catalítico
Ativação Enzimática/efeitos dos fármacos
Estabilidade Enzimática/efeitos dos fármacos
Feminino
Seres Humanos
Masculino
Fragmentos de Peptídeos/agonistas
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Agregação Plaquetária/efeitos dos fármacos
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteólise/efeitos dos fármacos
Protrombina/química
Protrombina/genética
Protrombina/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Inibidores de Serino Proteinase/farmacologia
Especificidade por Substrato
Subtilisina/antagonistas & inibidores
Trombose/etiologia
Trombose/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Peptide Fragments); 0 (Recombinant Proteins); 0 (Serine Proteinase Inhibitors); 78768-79-3 (prothrombin fragment 2); 9001-26-7 (Prothrombin); EC 3.4.21.62 (Subtilisin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.795245


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[PMID]:28658271
[Au] Autor:de Wolf ACMT; van Aalst S; Ludwig IS; Bodinham CL; Lewis DJ; van der Zee R; van Eden W; Broere F
[Ad] Endereço:Division of Immunology, Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands.
[Ti] Título:Regulatory T cell frequencies and phenotypes following anti-viral vaccination.
[So] Source:PLoS One;12(6):e0179942, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Regulatory T cells (Treg) function in the prevention of excessive inflammation and maintenance of immunological homeostasis. However, these cells may also interfere with resolution of infections or with immune reactions following vaccination. Effects of Treg on vaccine responses are nowadays investigated, but the impact of vaccination on Treg homeostasis is still largely unknown. This may be a relevant safety aspect, since loss of tolerance through reduced Treg may trigger autoimmunity. In exploratory clinical trials, healthy adults were vaccinated with an influenza subunit vaccine plus or minus the adjuvant MF59®, an adjuvanted hepatitis B subunit vaccine or a live attenuated yellow fever vaccine. Frequencies and phenotypes of resting (rTreg) and activated (aTreg) subpopulations of circulating CD4+ Treg were determined and compared to placebo immunization. Vaccination with influenza vaccines did not result in significant changes in Treg frequencies and phenotypes. Vaccination with the hepatitis B vaccine led to slightly increased frequencies of both rTreg and aTreg subpopulations and a decrease in expression of functionality marker CD39 on aTreg. The live attenuated vaccine resulted in a decrease in rTreg frequency, and an increase in expression of activation marker CD25 on both subpopulations, possibly indicating a conversion from resting to migratory aTreg due to vaccine virus replication. To study the more local effects of vaccination on Treg in lymphoid organs, we immunized mice and analyzed the CD4+ Treg frequency and phenotype in draining lymph nodes and spleen. Vaccination resulted in a transient local decrease in Treg frequency in lymph nodes, followed by a systemic Treg increase in the spleen. Taken together, we showed that vaccination with vaccines with an already established safe profile have only minimal impact on frequencies and characteristics of Treg over time. These findings may serve as a bench-mark of inter-individual variation of Treg frequencies and phenotypes following vaccination.
[Mh] Termos MeSH primário: Linfócitos T Reguladores/efeitos dos fármacos
Vacinas Virais/farmacologia
[Mh] Termos MeSH secundário: Adulto
Animais
Feminino
Vacinas contra Hepatite B/imunologia
Vacinas contra Hepatite B/farmacologia
Seres Humanos
Vacinas contra Influenza/imunologia
Vacinas contra Influenza/farmacologia
Contagem de Linfócitos
Masculino
Camundongos
Fragmentos de Peptídeos
Protrombina
Linfócitos T Reguladores/imunologia
Vacinas/imunologia
Vacinas/farmacologia
Vacinas Virais/imunologia
Vacina contra Febre Amarela/imunologia
Vacina contra Febre Amarela/farmacologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hepatitis B Vaccines); 0 (Influenza Vaccines); 0 (Peptide Fragments); 0 (Vaccines); 0 (Viral Vaccines); 0 (Yellow Fever Vaccine); 0 (chemotactic peptide CB67-129); 0 (fluad vaccine); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179942


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[PMID]:28658121
[Au] Autor:Saitta C; Raffa G; Alibrandi A; Brancatelli S; Lombardo D; Tripodi G; Raimondo G; Pollicino T
[Ad] Endereço:aDivision of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina bDepartment of Clinical and Experimental Medicine cDepartment of Economics dDepartment of Human Pathology, University of Messina, Messina, Italy.
[Ti] Título:PIVKA-II is a useful tool for diagnostic characterization of ultrasound-detected liver nodules in cirrhotic patients.
[So] Source:Medicine (Baltimore);96(26):e7266, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US.Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%).In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Cirrose Hepática/complicações
Neoplasias Hepáticas/sangue
Neoplasias Hepáticas/diagnóstico por imagem
Precursores de Proteínas/sangue
Ultrassonografia
[Mh] Termos MeSH secundário: Idoso
Área Sob a Curva
Biomarcadores Tumorais/sangue
Estudos de Coortes
Diagnóstico Diferencial
Feminino
Seguimentos
Seres Humanos
Fígado/diagnóstico por imagem
Cirrose Hepática/sangue
Cirrose Hepática/diagnóstico por imagem
Neoplasias Hepáticas/complicações
Masculino
Meia-Idade
Análise Multivariada
Protrombina
Curva ROC
alfa-Fetoproteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Biomarkers, Tumor); 0 (Protein Precursors); 0 (alpha-Fetoproteins); 53230-14-1 (acarboxyprothrombin); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007266


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[PMID]:28621228
[Au] Autor:Huang S; Jiang F; Wang Y; Yu Y; Ren S; Wang X; Yin P; Lou J
[Ad] Endereço:1 Clinical Laboratory Center, Beijing You'an hospital, Capital Medical University, Beijing, P.R. China.
[Ti] Título:Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.
[So] Source:Tumour Biol;39(6):1010428317705763, 2017 Jun.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better than alpha-fetoprotein in diagnosis of hepatitis B virus-related hepatocellular carcinoma patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Biomarcadores/sangue
Carcinoma Hepatocelular/sangue
Neoplasias Hepáticas/sangue
Precursores de Proteínas/sangue
alfa-Fetoproteínas/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/virologia
China
Feminino
Hepatite B/sangue
Hepatite B/patologia
Hepatite B/virologia
Vírus da Hepatite B/patogenicidade
Seres Humanos
Cirrose Hepática/sangue
Cirrose Hepática/patologia
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/virologia
Masculino
Meia-Idade
Protrombina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Biomarkers, Tumor); 0 (Protein Precursors); 0 (alpha-Fetoproteins); 53230-14-1 (acarboxyprothrombin); 9001-26-7 (Prothrombin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170622
[Lr] Data última revisão:
170622
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317705763



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