Abstract:
:The antithrombotic effect of MCI-9042, (+-)-2-(dimethyl-amino)-1-((o-(m- methoxyphenethyl)phenoxyl]methyl]ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmonary thromboembolic death. MCI-9042 reduced the mortality in a dose dependent manner and its ED50 value was 1.9 mg/kg po. Ticlopidine (TCP) which is a positive reference compound as an antithrombotic drug reduced the mortality at doses of 10 mg/kg po and above. Cyproheptadine (CPH) and ketanserin (KTS) which are S2-serotonergic antagonists were also effective on the reduction of mortality. In mesenteric arterial thrombosis induced by electric stimulation in mice, MCI-9042 prolonged the occlusion time resulted from platelet thrombus formation (PD50: 23 mg/kg po). CPH and KTS prolonged the occlusion time as potent as MCI-9042, but TCP prolonged the occlusion time only at the high doses of 100 mg/kg po and above. In experimental arterial thrombosis which generated in implanted polyethylene tubing, MCI-9042 reduced the incidence of thrombus formation in the tubing and its ED50 value was 18 mg/kg po. TCP was also effective in this model with an ED50 of 170 mg/kg po. The present results lead to the consideration that serotonin plays a more important role in thrombus formation than that conjectured formerly, and suggest that MCI-9042 becomes a new kind of antithrombotic drug with S2-serotonergic receptor antagonism.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Hara H,Kitajima A,Shimada H,Tamao Ysubject
Has Abstractpub_date
1991-10-01 00:00:00pages
484-8issue
4eissn
0340-6245issn
2567-689Xjournal_volume
66pub_type
杂志文章abstract::FPA level, fibrinogen turnover rate, and fibrinolytic activity were studied on 18 patients with malignant disease. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r = 0.74, p less than 0.001) and FDP (r - 0.58, p less than 0.02). Estimated FPA turnover ra...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-12-23 00:00:00
abstract::Carbamylation is a non-enzymatic post-translational modification induced upon exposure of free amino groups to urea-derived cyanate leading to irreversible changes of protein charge, structure and function. Levels of carbamylated proteins increase significantly in chronic kidney disease and carbamylated albumin is con...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-09-0704
更新日期:2017-05-03 00:00:00
abstract::The macromolecular composition of the extracellular matrix (ECM) produced by the human microvascular endothelial cell line (HMEC-1) was determined by ELISA and its thrombogenicity was studied in blood perfusion assays. Results were compared with those obtained with the ECM produced by human umbilical vein endothelial ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Hyperinsulinemia predicts future cardiovascular events, but may also contribute to atherosclerosis. We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3'-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, togeth...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-02-01 00:00:00
abstract::In order to investigate the reported heterogeneity of commercial heparin injections, lung and mucous preparations were fractionated by gel chromatography according to molecular size. Eluent pools were characterized by measuring electrophoretic mobility, anticoagulant activity using a reactivation assay and an anti-Xa ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-02-29 00:00:00
abstract::Amniotic fluid inhibited the fibrinolytic, amidolytic and esterolytic activity of urokinase. Kinetic studies with AGLMe demonstrated non-competitive inhibition. A major part of the inhibitory activity could be separated from alpha 1-antitrypsin by ion-exchange chromatography on DEAE-Sephadex A-50. Plasminogen activato...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-08-29 00:00:00
abstract::Wide variations in procoagulant properties, lipid composition and ultrastructure of five commonly used APTT methods have been demonstrated. Performance of the methods with a range of coagulation abnormalities has been ranked. Most of the reagents obtained a high score with one or more defects, but a low score with oth...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-04-30 00:00:00
abstract::Recombinant factor VIIa (rFVIIa: NovoSeven; Novo Nordisk) has proven efficacy in the treatment of haemophilic patients with inhibitors. This prospective, double-blind study compared rFVIIa (35 vs. 90 microg/kg) in the initiation and maintenance of haemostasis during and after elective surgery. Patients with inhibitors...
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:1998-11-01 00:00:00
abstract::The contribution of the various components of the contact system in the generation of factor XIIa (FXIIa) and of kallikrein (KRN) on an electronegative surface and the release of the generated enzymes to the bulk phase was examined in mixtures of normal human plasma and plasmas congenitally deficient in these componen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::This study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperativ...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-10-01 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::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::Underlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from ve...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::A patient with an 18 year history of recurrent arterial thrombosis and no evidence of atherosclerosis or embolism of cardiac origin presented with a prolonged thrombin clotting time when performed with human thrombin. The bovine thrombin clotting time was only slightly prolonged. During 30 months of follow-up, the thr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-02-03 00:00:00
abstract::The leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin's rapid clearance from the circulation. We previously employed albumin fusion to slow hirudin variant 3 (HV3) clearance. In this study, we hypothesized th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-05-01 00:00:00
abstract::Findings from a recent study suggest that earlier start of treatment with factor VIII in patients with severe hemophilia is associated with a higher risk to develop inhibitors. We set out to assess the association between age of first administration of clotting factor VIII and the risk to develop inhibitors in infants...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::Thrombin incubated with 2,3-diphosphoglycerate (150 nmol 2,3-DPG/1 NIH thrombin unit) lost up to 70% of its clotting activity, whereas the esterase activity remained unchanged. No fibrinopeptide release by thrombin was observed in the presence of 2,3-DPG. The fibrin polymerization was normal. By chromatography on Ambe...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-10-01 00:00:00
abstract:: ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1657075
更新日期:1979-07-01 00:00:00
abstract::The effect of supernatant from phorbol myristate acetate (PMA) stimulated human polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro. The supernatant caused a rapid loss in factor VII coagulant activity by the action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as demo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析,评审
doi:10.1160/TH11-02-0116
更新日期:2011-09-01 00:00:00
abstract::Thrombin-induced platelet release reaction examined with secretion of calcium and N-acetylglucosaminidase was significantly enhanced in the platelets from reserpine-treated rabbits as compared with the control. On the other hand, 32P-incorporation into phosphatidic acid was suppressed in the reserpinized platelets in ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-08-30 00:00:00
abstract::The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathological data of 10 years w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-08-0632
更新日期:2014-03-03 00:00:00
abstract::In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain.We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-04-0305
更新日期:2015-03-01 00:00:00
abstract::In order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and seru...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-06-28 00:00:00
abstract::Platelets are not only centrally involved in haemostasis, but also in antimicrobial defence and inflammation. Since evaluation of platelet physiology in the particular patient group of preterm and term neonatal infants is highly restricted for ethical reasons, there are hardly any data available in healthy and much le...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-05-0476
更新日期:2015-01-01 00:00:00
abstract::Research into cancer-associated thrombosis (CAT) entails managing dynamic data that pose an analytical challenge. Thus, methods that assume proportional hazards to investigate prognosis entail a risk of misinterpreting or overlooking key traits or time-varying effects. We examined the AGAMENON registry, which collects...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0039-1694012
更新日期:2019-11-01 00:00:00
abstract::The correlation between homocysteine and vascular disease has been assessed in several clinical studies that demonstrated that elevation of plasma total homocysteine (tHcy) was an independent risk factor for atheriosclerotic disease. Major advances of homocysteine metabolism disorders have been made during the last fe...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH09-06-0393
更新日期:2010-05-01 00:00:00
abstract::This study assessed the abundance and activity of thrombin in human thrombi. removed at autopsy or during surgery. Arterial and venous thrombus sections showed thrombin activity by in situ zymography, based on conversion of fibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activity. Thrombin activi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::The ADP-induced release of 3H-serotonin from human platelets in heparinized platelets rich plasma is markedly stimulated by the addition of sodium citrate. The aggregation and release that is induced by collagen is less affected by citrate. Data is presented that supports the view that the effects of citrate on both A...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-08-31 00:00:00
abstract::Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial...
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/TH15-06-0452
更新日期:2015-11-25 00:00:00