Abstract：
:An amidrazonophenylalanine derivative, LB30057, inhibits the catalytic activity of thrombin potently by interaction with the active site of thrombin, and has high water solubility. In the present study, we evaluated the effect of LB30057 on the biological activities of thrombin at various tissues, and determined whether thrombin inhibition by LB30057 could reduce the incidence of occlusive thrombosis in an in vivo animal model. Treatment with LB30057 to human plasma prolonged clotting times in a concentration-dependent manner. LB30057 suppressed significantly thrombin-induced phosphatidylserine (PS) exposure in platelets, suggesting that LB30057 could inhibit blood coagulation accelerated by PS exposure. In human platelets, soluble thrombin- and clot-induced platelet aggregation was inhibited by LB30057 potently. Consistent with this finding, LB30057 showed concentration-dependent inhibitory effects on serotonin secretion and P-selectin expression induced by thrombin in platelets. In the blood vessel isolated from the guinea pig, treatment with LB30057 resulted in a concentration-dependent inhibition of thrombin-induced vascular contraction. In vivo study revealed that LB30057 following oral administration significantly increased the time to occlusion and improved carotid arterial patency using rat carotid artery thrombosis model. All these results suggest that LB30057 is a potent inhibitor of biological activities of thrombin at various target tissues and, therefore, might be developed as an antithrombotic agent for treatment and prevention of thrombotic diseases.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Kang KT,Jung BI,Bae ON,Lee MY,Chung SM,Lee JY,Lee SK,Kim IC,Chung JHkeywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
104-11issue
1eissn
0340-6245issn
2567-689Xpii
03010104journal_volume
89pub_type
杂志文章abstract：:The functional activity and active site of plasmin in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen described in a previous paper. The functional activity of newborn plasminogen measured on chromogenic substrate w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:Using gain-of-function factor IX (FIX) for replacement therapy for haemophilia B (HB) is an attractive strategy. We previously reported a high-activity FIX, FIX-Triple (FIX-V86A/E277A/R338A) as a good substitute for FIX-WT (wild-type) in protein replacement therapy, gene therapy, and cell therapy. Here we generated a ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH13-02-0154
更新日期：2013-08-01 00:00:00
abstract：:The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates fo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH14-01-0078
更新日期：2014-09-02 00:00:00
abstract：:Sequential treatment of arterial occlusions of the leg with porcine plasmin and low dose streptokinase results in a strong systemic proteolysis as already seen in deep leg vein thrombosis. In 31 of 45 patients the blood flow through major arterial segments could be restored. Thrombolytic success is possible within the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
abstract：:Tissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atheroge...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-08-01 00:00:00
abstract：:The present studies measured bleeding times, without venous occlusion, in a series of patients, whose bleeding times (+ venostasis) consistently exceeded 20 min. During these tests, the amount of blood loss (expressed as mg/min) was also quantitated. To allow comparison, normal controls were studied before and followi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:AZD0837 is an investigational oral anticoagulant which is converted to the active form, AR-H067637, a selective direct thrombin inhibitor. The present study, a multicentre, randomised, parallel-group, dose-guiding study, assessed the safety and tolerability of an immediate-release formulation of AZD0837 compared with ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1160/TH09-07-0509
更新日期：2010-03-01 00:00:00
abstract：:A study was made of the influence of thrombin on the platelet-aggregating activity of human factor VIII with Ristocetin as cofactor. Purified factor VIII and different amounts of a thrombin-Sepharose 2B complex were mixed and incubated for various periods of time. The factor VIII-related platelet-aggregating activitie...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1979-10-31 00:00:00
abstract：:We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D(1) domain-containing plasmic fragments such as fragments X,Y, and D(1), but not intact fibrinogen or cross-linked fibrin degradation p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:We tested the response of the fibrinolytic activity and factor VIII-antigen levels to infusion of DDAVP in healthy volunteers and we studied the influence of propranolol and aspirin on this response. After DDAVP, 0.4 microgram/kg in 10 min i.v., the fibrinolytic activity of redissolved euglobulins rose from 179 to 452...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:A fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-111-oxine. The recovery of the total platelet population in the circulation was 85% +/- 9. Mean platelet life span was 146 hr +/- 13. Correcting for plasma radioactivity (alway...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
abstract：:Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationshi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH17-02-0085
更新日期：2017-08-01 00:00:00
abstract：:Fucoïdans catalyse thrombin inhibition by antithrombin (AT) and heparin cofactor II (HCII); their affinity for each serpin varies according to the seaweed species from which they are extracted, as well as their chemical composition and molecular weight. We extracted a homogeneous fucoïdan fraction from Ascophyllum nod...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Lenalidomide, a derivate of thalidomide, has recently been approved in Europe for the treatment of patients with multiple myeloma. Although the substance has a better effect/side-effect profile, especially with regard to teratogenicity and neurotoxicity, the rate of therapy-induced thrombosis seems comparable to thali...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH08-01-0009
更新日期：2008-06-01 00:00:00
abstract：:Genetic determinants of venous thromboembolism (VTE) in the African-American population are poorly characterised. It was recently shown that fibrinogen gamma gene (FGG) polymorphisms 10034C>T and 9340T>C influence VTE risk in the Caucasian population. In the African-American population these polymorphisms are common, ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2009-06-01 00:00:00
abstract：:We examined the effect of a synthetic thrombin inhibitor, MCI-9038, on two experimental animal models of disseminated intravascular coagulation (DIC). In a model that DIC induced by the intravenous infusion of thrombin, MCI-9038 suppressed the decrease of platelet count by about 50% at a dose of 0.2 micrograms/kg/min ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-04-07 00:00:00
abstract：:Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP pa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH12-07-0522
更新日期：2013-04-01 00:00:00
abstract：:Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet aggregation in ambulatory patients with symptomatic atheros...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1999-11-01 00:00:00
abstract：:Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) depen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1995-07-01 00:00:00
abstract：:Excessive leukocyte infiltration causes severe tissue damage in a variety of inflammatory diseases. The initial step in leukocyte extravasation is mediated by selectins and oligosaccharides on their glycoconjugate ligands. Human milk is a rich source of lactose-derived oligosaccharides that are partly absorbed in the ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-01-0055
更新日期：2004-12-01 00:00:00
abstract：:We examined the ability of unfractionated heparin to modulate the procoagulant activities of stimulated endothelial cells (EC). Confluent human venous umbilical EC were incubated with heparin before or after stimulation, then rinsed extensively to eliminate any heparin in the solution. EC, stimulated for 4 h with endo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Vitamin K-dependent proteins are currently purified from pooled human plasma or produced in mammalian cell culture systems by recombinant DNA technology. Transgenic animals may provide an additional expression system for the production of these therapeutic proteins. Mice have been used to test hybrid genes which direc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:Following exposure of rats to graded doses of fresh cigarette smoke, the aortic endothelium examined by scanning electron microscopy regularly showed alterations. These essentially consisted of areas of blebbing and microvillus-like projections from the luminal surface, and the presence in the majority of cases, of mi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
abstract：:Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no information is available as to what extent the kinetics of complex formation between TFPI and factor Xa during factor X activation contribute to the overall ra...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:The standard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin. This entails hospitalisation, nursing care, immobility and repeated laboratory tests (e.g. activated partial thromboplastin time [APTT], platelet count). In addition approximately 10% of patients suffe...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：1991-03-04 00:00:00
abstract：:The influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-01-23 00:00:00
abstract：:It has been experimentally shown that endotoxin induces a significant increase in the blood levels of a plasminogen activator inhibitor (PAI). We evaluated the effect of different doses of heparin (5 to 20 IU kg-1 h-1), antithrombin III (10 to 40 U kg-1 h-1 and 240 U/kg as bolus) and of a combination of the two on: 1)...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-09-29 00:00:00
abstract：:A new method to determine the concentration of free protein S in plasma is described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to capture the free protein S from plasma samples. The use of C4BP as ligand in the assa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:Most of the knowledge acquired on platelet function and biochemistry has been obtained from platelets prepared from blood anticoagulated with sodium citrate. Using washed platelets from human blood (PNB) to which no anticoagulants were added, we report on responses not observed with platelets prepared from citrate-ant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-10-21 00:00:00
abstract：:The vast majority of thrombin (>95%) is generated after clotting is completed, suggesting that thrombin formation serves purposes beyond coagulation, such as tissue repair after vessel injury. Two types of vascular thrombin binding sites exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their express...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-09-0627
更新日期：2010-05-01 00:00:00
