Abstract:
:The potent inhibitor of platelet cAMP phosphodiesterase (PDE) HL 725 (9,10-Dimethoxy-2-mesitylimino-3-methyl-3, 4,6,7-tetrahydro-2H-pyrimido(6,1-A)-isoquinoline-4-one-hydrochloride), was examined for its effects on human and rat platelet aggregation. Strong inhibitory effects are seen on collagen-induced platelet aggregation both in rat platelet-rich plasma (PRP) (IC50, 54 +/- 12 nM) and whole blood (IC50, 57 +/- 25 nM). Compared to the effects on rat platelets, HL 725 is about two-fold less inhibitory in human PRP (IC50, 94 +/- 29 nM) and whole blood (IC50, 126 +/- 50 nM). The inhibitory action of HL 725 can be reversed by washing and resuspension of the platelets, suggesting that HL 725 does not bind tightly to cAMP PDE. If human or rat PRP is pretreated with adenosine deaminase, an enzyme that degrades adenosine or 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, the inhibitory effect of HL 725 is reversed. Similar blockade of the inhibitory actions of several other inhibitors of cAMP PDE such as RA 233, RX-RA 69 (analogs of dipyridamole) and oxagrelate is seen by adenosine deaminase pretreatment. The nucleoside transport inhibitors, dilazep and dipyridamole which are non-inhibitory alone to platelet aggregation, strongly potentiate (about 10-fold) the inhibitory action of HL 725 on collagen-induced platelet aggregation in human whole blood. However, if the whole blood is pretreated with adenosine deaminase, no inhibitory effect of dipyridamole plus HL 725 is seen on platelet aggregation. These studies demonstrate that plasma adenosine plays a crucial role in the antiaggregatory actions of HL 725 and several other inhibitors of cAMP PDE both in human and rat blood.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Agarwal KC,Buckley RS,Parks RE Jrdoi
10.1016/0049-3848(87)90376-8subject
Has Abstractpub_date
1987-07-15 00:00:00pages
191-200issue
2eissn
0049-3848issn
1879-2472journal_volume
47pub_type
杂志文章abstract::Bleeding is an important complication of heparin therapy. A number of low molecular weight heparin fractions produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. Low molecular weight heparin fractions and fragments are produced by a number of different procedures...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90265-2
更新日期:1984-09-15 00:00:00
abstract:INTRODUCTION:To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT. MATERIALS/METHODS:187 patients started on pDTI for ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.04.030
更新日期:2014-07-01 00:00:00
abstract::Platelet adherence and aggregation are important in the development of ischemic sequelae in atherosclerosis. To directly examine platelet interaction with plaque, everted, deendothelialized aortic fibrous plaques from Watanabe-heritable hyperlipidemic rabbits were exposed to flowing human blood in an annular perfusion...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90040-6
更新日期:1989-04-15 00:00:00
abstract::Addition of two commercial luciferin-luciferase reagents caused marked inhibition of the aggregatory response of washed human platelets to thrombin, ADP, vasopressin and platelet-activating factor (PAF). Analysis of the effects of the individual components of one of these reagents revealed that Mg2+, and to a lesser e...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90053-2
更新日期:1985-04-15 00:00:00
abstract::Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer patients undergoing routine computed tomography scans for staging purposes or treatment response evaluation. The reported incidence of UPE ranges from 1% to 5% which probably represents an underestimation. A significant proportion of can...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(14)50028-X
更新日期:2014-05-01 00:00:00
abstract::This study examined the effect of exercise on plasma fibrinogen concentrations with simultaneous measurements of plasma volume changes. Eight moderately active males aged 26.6+/-3.6 years (mean +/- SD) completed maximal (VO2max) and submaximal (75% VO2max for 30 minutes) exercise trials separated by 7 days. Venous blo...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/s0049-3848(99)00140-1
更新日期:1999-12-15 00:00:00
abstract::Ten studies of the effect of cryoprecipitate infusion in four patients with von Willebrand's Disease (vWD) are reported. The doses studied (4, 8 and in one case 10 bags of cryoprecipitate) were based on previous reports of correction of the bleeding time (BT) with such doses. A modest shortening of the BT was observed...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90196-5
更新日期:1989-03-01 00:00:00
abstract::The extrinsic pathway of coagulation is initiated when zymogen factor VII binds to its cell surface receptor tissue factor. Recently recombinant human tissue factor has become available and therefore in this study the direct binding of human factor VII in plasma to recombinant tissue factor was explored. Factor VII bi...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90103-u
更新日期:1993-05-15 00:00:00
abstract:INTRODUCTION:Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis. MATERIALS AND METHODS:A Delphi exercise ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.01.012
更新日期:2010-08-01 00:00:00
abstract::Human tissue plasminogen activator (t-PA) was shown to bind specifically to human osteosarcoma cells (HOS), and human epidermoid carcinoma cells (A-431 cells). Crosslinking studies with DTSSP demonstrated high molecular weight complexes (130,000) between 125I-t-PA and cell membrane protein on human umbilical vein endo...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90136-z
更新日期:1990-07-15 00:00:00
abstract::The immunoglobulin superfamily member EMMPRIN (CD147) plays an important role in a number of organ systems, including the cardiovascular system. Here we review the contemporary understanding of EMMPRIN and EMMPRIN-associated sequelae in the course of atherosclerosis. A significant body of data documents the pivotal ro...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2013.04.017
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:The quality of treatment with warfarin is mainly assessed by the time in therapeutic range (TTR) in patients with mechanical heart valve prosthesis (MHV). Our aim was to evaluate if International Normalized Ratio (INR) variability predicted a combined endpoint of thromboembolism, major bleeding and death bet...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.10.044
更新日期:2015-12-01 00:00:00
abstract:INTRODUCTION:Atherosclerosis, the underlying disorder of coronary artery disease (CAD), is an inflammatory process involving multiple molecular pathways. Chemokine-mediated mechanisms are potent regulators of atherosclerosis. Genetic variations that alter such signaling pathways could affect susceptibility to CAD. We i...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2005.12.016
更新日期:2007-01-01 00:00:00
abstract::Patients with the nephrotic syndrome are at increased risk of developing venous and arterial thromboembolism, the most common of which is renal vein thrombosis. There are several unanswered or controversial issues relating to the nephrotic syndrome and thromboembolism, which include the mechanism of thromboembolism, a...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2005.03.030
更新日期:2006-01-01 00:00:00
abstract::We investigated the intracellular processes of the shape change in human megakaryoblastic leukemic cells, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by phorbol 12-myristate 13 acetate (TPA) and weakly by Ca2+ ionophore, A23187, but not by ADP, co...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90130-3
更新日期:1992-10-01 00:00:00
abstract::The soluble fibrin monomer complexes (SFMC) in 154 obstetric patients with possible disseminated intravascular coagulation (DIC) were evaluated in SDS polyacrylamide gel electrophoresis (PAGE) after precipitation with B-alanine. Other coagulation tests were performed on these patients. The patients were classified int...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90007-x
更新日期:1982-09-15 00:00:00
abstract::Capsaicin was found to be a potent inhibitor of platelet aggregation and release reaction. It inhibited the aggregation of rat platelet induced by collagen and thrombin, but only slightly reduced those of AA and A23187. The IC50 on collagen-induced platelet aggregation was about 85 micrograms/ml. Less inhibition was o...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90189-0
更新日期:1984-12-15 00:00:00
abstract::We report an inbred family with two cases of homozygous protein C deficiency and review 11 other such cases. Both patients presented in the second half of their first year of life with recurrent rapidly disappearing ecchymotic skin lesions, disseminated intravascular coagulation, and venous thrombosis. Successful trea...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/0049-3848(89)90202-8
更新日期:1989-03-01 00:00:00
abstract::Two anti-cardiolipin antibody (ACA)-producing cell lines were established, using Epstein-Barr virus transformation followed by a repeated cluster-picking from the same individual with antiphospholipid syndrome who had a history of 8 consecutive fetal losses and deep venous thrombosis. Characterization of the two ACAs ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90037-x
更新日期:1994-04-01 00:00:00
abstract:INTRODUCTION:Clinical trials have provided evidence about efficacy and safety of extended thromboprophylaxis among total hip replacement (THR) patients. There is a lack of evidence on effectiveness and safety of extended treatment in unselected patients from routine clinical practice. We examined the effectiveness and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.11.029
更新日期:2015-02-01 00:00:00
abstract::The ability of the COA-SET Fibrin monomer (COA-SET FM) test to detect soluble fibrin was evaluated by comparing the results of the COA-SET FM test with fibrinopeptide A (FPA) determinations following thrombin incubation of plasma or whole blood. In addition, two semiquantitative tests (erythrocytes-agglutination test ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90066-l
更新日期:1990-02-15 00:00:00
abstract::Bleeding events are a common adverse effect in oral anticoagulation that frequently depend on the duration and intensity of treatment. Major bleeding events, particularly intracerebral hemorrhages, are a serious complication in cases that require the rapid reversal of anticoagulation. Urgent correction of the coagulat...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(99)00085-7
更新日期:1999-08-15 00:00:00
abstract::The effects of ticlopidine treatment (250 mg b.i.d. for 21 months) on fibrinogen and other rheological variables, as compared to placebo, were studied in 44 patients with intermittent claudication due to peripheral arterial occlusive disease. Blood samples were collected every 3 months during this double-blind, random...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(88)90134-x
更新日期:1988-12-15 00:00:00
abstract:INTRODUCTION:Bleeding after cardiac surgery may be caused by surgical factors, impaired haemostasis, or a combination of both. Transfusion of blood products is used to improve haemostasis, but little is known about what combination is optimal. We hypothesized that addition of both fibrinogen and platelets to blood samp...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.05.023
更新日期:2014-10-01 00:00:00
abstract:INTRODUCTION:Different Klebsiella pneumoniae strains carry different virulence factors and antibiotic resistance and may cause thrombocytopenia. This study aimed to investigate the effects of different infections caused by K. pneumoniae on platelets. METHODS:Two hypermucoviscous K. pneumoniae strains and two classic s...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.09.053
更新日期:2018-11-01 00:00:00
abstract::To determine whether homocysteine, a risk factor for possible endothelial cell dysfunction, procoagulant effects and premature vascular disease but with a potential nutritional role for fetal and neonatal metabolism and development, is elevated in women at time of elective caesarean section with nitrous oxide general ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2003.11.004
更新日期:2003-01-01 00:00:00
abstract::The use of oral contraceptives (OCs) has been associated with vascular complications. The mechanism(s) by which OCs predispose to thrombotic events remains unclear. Recent studies have demonstrated that postmenopausal (PM) women who take estrogen replacement therapy (ERT) have a decreased incidence of myocardial infar...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90043-n
更新日期:1993-01-15 00:00:00
abstract::We tested whether inhibition of platelet activation by nitric oxide (NO) might be altered by strenuous exercise. Sixteen healthy male non-smokers, aged 20-26 years, underwent treadmill testing. All subjects reached Bruce stage IV without chest pain or abnormal ST-T wave changes. Platelet aggregation by Born's method a...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00162-x
更新日期:1997-09-01 00:00:00
abstract:INTRODUCTION:Tissue factor (TF) is abnormally expressed in many cancers including colorectal and is associated with a poor cancer prognosis. Colorectal cancer cell lines expressing TF produce faster growing tumours. In lung cancer, TF inhibition has been shown to reduce proliferation AIM:We aimed to determine if TF ex...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(16)30183-9
更新日期:2016-04-01 00:00:00
abstract::The antithrombotic actions of selective factor Xa (FXa) inhibitors, recombinant tick anticoagulant peptide (rTAP) and DX-9065a, were evaluated in experimental thrombosis models in anesthetized rats. In the first model, thrombosis was induced by exposing flowing blood to a silk thread anchored in an arteriovenous (AV) ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00112-0
更新日期:1996-07-15 00:00:00