Abstract：
:RS-5186, sodium 6-[2-[1-(1H)-imidazolyl]methyl-4,5-dihydrobenzo[b]thiophene]- carboxylate, inhibited platelet thromboxane A2 (TXA2) synthetase with IC50 values of 6 nM and 13 nM for human and rabbit microsomes, respectively. It had a selectivity for TXA2 synthetase 10(5)-fold greater than that for cyclooxygenase, PGI2 synthetase, 5-lipoxygenase and phospholipase A2. When administered orally or intravenously to dogs at 1 mg/kg, RS-5186 suppressed serum TXB2 levels almost completely with sustained duration of action: the suppression during 0.5 hr to 8 hr after dosing was more than 90%, and was 70-80% at 24 hr. Similar suppression of serum TXB2 levels was observed in rats and rabbits. Such suppression by RS-5186 was more potent than that by OKY-046 and CV-4151. Serial administration of RS-5186 (0.1 mg/kg/day p.o.) to dogs for 7 days decreased the serum TXB2 levels constantly during the medication, and no rebound phenomenon was observed after the medication was stopped. In a thrombotic model induced by sodium arachidonate injection in rabbits, RS-5186 at 1 mg/kg p.o. completely protected against sudden death (ED50 = 0.12 mg/kg, 1 hr after dosing) and this protective effect extended over 8 hr. All these results show that RS-5186 is a potent and highly selective TXA2 synthetase inhibitor with a long duration of action, and suggest that the compound could be useful in diseases where TXA2 is involved.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Ushiyama S,Ito T,Asai F,Oshima T,Terada A,Matsuda K,Yamazaki Mdoi
10.1016/0049-3848(88)90116-8subject
Has Abstractpub_date
1988-09-01 00:00:00pages
507-20issue
5eissn
0049-3848issn
1879-2472pii
0049-3848(88)90116-8journal_volume
51pub_type
杂志文章abstract：:Human and bovine alpha-thrombins (greater than 90% alpha form) with high fibrinogen clotting activities (approximately 3,000 U.S. units/mg protein) exhibit similar Michaelis menten kinetics with the p-nitroanilide tripeptide substrates Tos-Gly-Pro-arg-pNA (Chromozym-TH) and D-Phe-Pip-Arg-pNA (S-2238). The kinetic para...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90114-1
更新日期：1982-11-01 00:00:00
abstract：:In spite of numerous studies on the involvement of fibrinogen in transendothelial migration of leukocytes and thereby inflammation, there is still no clear understanding of which fibrin(ogen) species can stimulate leukocyte transmigration. Although we have previously proposed that interaction of fibrin with the VLDL r...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2017.11.007
更新日期：2018-02-01 00:00:00
abstract：:The concentration of tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and the complex of t-PA and PAI-1 (t-PA-PAI-1 complex) were measured using an enzyme immunoassay, where the first antibody was monoclonal antibody against PAI-1 and the second one was polyclonal anti-t-PA Fab' antibody....
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90392-7
更新日期：1989-09-01 00:00:00
abstract：INTRODUCTION:Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese. METHODS:We recruited 161 CHD patients and 112 controls pr...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析
doi：10.1016/j.thromres.2012.05.023
更新日期：2012-10-01 00:00:00
abstract：INTRODUCTION:Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes. METHODS:This was a retrospective claims analysis involving administrative claims data and in-pati...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.08.013
更新日期：2013-11-01 00:00:00
abstract：INTRODUCTION:Lung cancer is the leading cause of cancer-related death worldwide. Small cell lung cancer (SCLC) is thereby a highly aggressive neuroendocrine carcinoma representing about 15% of all lung cancer cases. Due to the highly metastatic behavior and multidrug resistance, the long-term survival of patients is ve...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/S0049-3848(16)30166-9
更新日期：2016-04-01 00:00:00
abstract：INTRODUCTION:Procoagulant activity of heparanase has been recently described in several arterial and venous thrombotic disorders. In this study, we aimed to investigate the role of heparanase with regard to thrombus burden, thromboembolism, and treatment success with unfractionated heparin (UFH) in patients with prosth...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2018.09.061
更新日期：2018-11-01 00:00:00
abstract：:The effect of warfarin-induced factor VII deficiency on the skin bleeding time was investigated in 10 consecutive patients with mean prothrombin times of 33 sec and factor VII levels of 7%. Bleeding times in all but one subject were entirely within the normal range. We conclude that warfarin administration, even to th...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(83)90243-8
更新日期：1983-02-15 00:00:00
abstract：INTRODUCTION:Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, a...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.07.003
更新日期：2013-08-01 00:00:00
abstract：INTRODUCTION:An individualised thromboprophylaxis was implemented in critically ill patients suffering from coronavirus disease 2019 (COVID-19) pneumonia to reduce mortality and improve clinical outcome. The aim of this study was to evaluate the effect of this intervention on clinical outcome. METHODS:In this mono-cen...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2020.07.038
更新日期：2020-10-01 00:00:00
abstract：BACKGROUND:Abdominal obesity has been found to be associated with an increased risk of deep vein thrombosis (DVT). Whether patients with abdominal obesity have an increased risk of recurrence is currently unknown. METHODS:Patients with objective diagnosis of DVT and a life expectancy of greater than 6 months underwent...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2006.05.013
更新日期：2007-01-01 00:00:00
abstract：:The effect of tissue factor pathway inhibitor (TFPI) on thrombin and factor Xa generation was studied in an in vitro system using a prothrombin complex concentrate. It was found that TFPI, via the direct inhibition of factor Xa and the tissue factor/factor VIIa complex, inhibited both the further generation of factor ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(94)90173-2
更新日期：1994-09-15 00:00:00
abstract：:Prothrombin time is a standard screening test to monitor patients treated with oral anticoagulants. We hypothesize that INR measurements will not vary a lot within a given day in a given patient. The present study was thus conducted to compare the change of the international normalized ratio (INR) of prothrombin time ...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章
doi：10.1016/s0049-3848(02)00339-0
更新日期：2002-09-01 00:00:00
abstract：INTRODUCTION:High RDW values are associated with adverse prognosis in many clinical conditions including short and medium term outcome of patients with ST Elevation Myocardial Infarction (STEMI). The aim of the present study was to evaluate the association between RDW and long term mortality in STEMI patients undergoin...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.08.016
更新日期：2014-11-01 00:00:00
abstract：:Anticoagulant fucoidan fractions of different molecular weight and sulfate content were prepared and investigated for their effects on platelet function in vitro. The fucoidan fractions were incubated with human platelet rich plasma (PRP) at concentrations of 5, 10 and 50 micrograms/ml. Platelet activation was subsequ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(97)00037-6
更新日期：1997-03-15 00:00:00
abstract：INTRODUCTION:Inflammation and coagulation play important roles in the pathogenesis of sepsis. Anticoagulants with anti-inflammatory action draw attention as therapeutic agent in sepsis. OBJECTIVE:Whether cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2-(1H)-quinolinone), anticoagulant, protects m...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.06.017
更新日期：2015-08-01 00:00:00
abstract：BACKGROUND:The optimal prevention measures against hemodialysis (HD)-associated complications, including all-cause thrombotic events and death, are unclear. METHODS:This prospective study was designed to assess the effect of aspirin on prevention of HD-associated complications. Patients were divided into four groups a...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.04.023
更新日期：2015-07-01 00:00:00
abstract：INTRODUCTION:In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2016.12.020
更新日期：2017-02-01 00:00:00
abstract：:A new approach to the investigation of accumulation of acridine derivatives and release by platelets is proposed. At high concentrations of acridine orange (AO) inside dense bodies, a two component fluorescence spectrum with maxima at 530 and 640 nm has been recorded. Computer deconvolution of spectra provided additio...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(87)90102-2
更新日期：1987-09-15 00:00:00
abstract：INTRODUCTION:Unfractionated heparin (UFH) potentiates platelet aggregation induced by some agonists. P2Y12 and P2Y1 receptors play a major role in amplifying platelet aggregation. We assessed the ability of cangrelor, a selective P2Y12 antagonist, A2P5P, a selective P2Y1 antagonist, and aspirin to block the potentiatin...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2004.09.004
更新日期：2005-01-01 00:00:00
abstract：:In this study, we investigated the effects of a 3-min insulin incubation both at physiological and at supraphysiological concentrations on platelet aggregation and intraplatelet cyclic guanosine monophosphate (cGMP) levels both in the absence and in the presence of phosphodiesterase inhibition. We observed that insuli...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(96)00051-5
更新日期：1996-04-01 00:00:00
abstract：:Mass-Length ratio of fibrin fibres (microT and microP) derived independently from turbidity and permeability respectively, in networks made in fibrinogen solution and plasma, have been compared under similar conditions of clotting. Amount of fibrinogen conversion to fibrin was similar in both systems when high thrombi...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(87)90193-9
更新日期：1987-02-01 00:00:00
abstract：OBJECTIVES:To measure the variations of different parameters in the hemostatic system and to analyze their roles in the development of hemostatic disorder in patients with orthotopic liver transplantation (OLT) procedures routinely performed without venovenous bypass. METHODS:The blood coagulation and fibrinolysis par...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2007.10.002
更新日期：2008-01-01 00:00:00
abstract：:We investigated the relationship between the procoagulant protease-inhibitory activity and the N-glycan structures in urinary protein C inhibitor (uPCI) by sequential exoglycosidase digestions based on the N-glycan structures elucidated in this report. uPCI was glycosylated on the three potential N-glycosylation sites...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(01)00342-5
更新日期：2001-10-01 00:00:00
abstract：BACKGROUND:Platelet microparticles (PMPs) possess proatherogenic and procoagulant properties which may play a role in atherogenesis and subsequent thromboembolic complications. The present study was conducted to investigate the possible relationship between carotid atherosclerosis and plasma concentrations of PMPs, and...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2008.10.016
更新日期：2009-04-01 00:00:00
abstract：:When a purified myeloma protein with the ability to inhibit fibrin polymerization was preincubated with sheep anti-human F(ab')2 antibodies, there was a marked reduction of the ability to prolong the thrombin clotting time, while anti-Fc antibodies had only a slight effect. A monoclonal immunoglobulin which shortens t...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90284-1
更新日期：1985-11-15 00:00:00
abstract：INTRODUCTION:Although the general improvement caused by recombinant human erythropoietin (rHuEPO) in the correction of uraemic anaemia cannot be questioned, some data suggest that the changes in the haemostasis, endothelial function and oxidative stress (SOX) are induced. The aim of the present study was to investigate...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章
doi：10.1016/j.thromres.2007.02.004
更新日期：2007-01-01 00:00:00
abstract：:The antithrombotic effect of aspirin (ASA) and dipyridamole (DIP) was evaluated in rabbits in which platelet thromboxane A2 (TXA2) and arterial prostacyclin (PGI2) were measured. An intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents was used. Prostaglandins were determined by...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(83)90224-4
更新日期：1983-05-15 00:00:00
abstract：INTRODUCTION:Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Ou...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析
doi：10.1016/j.thromres.2014.10.007
更新日期：2015-01-01 00:00:00
abstract：:Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet, relatively high concentrations (approximately 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines shoul...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(84)90160-9
更新日期：1984-02-01 00:00:00
