Abstract：
INTRODUCTION:Excessive platelet activation fundamentally contributes to cardiovascular events and mortality in patients with diabetes mellitus. Functional resistance has been described for current antiplatelet therapies in broad populations that include patients with diabetes. We investigated acute and chronic effects of AZD6140, a reversible oral rapid-onset P2Y(12) antagonist, on platelet reactivity in diabetic rats. MATERIALS AND METHODS:Diabetes was induced by streptozotocin injection in male Wistar rats. After 4 weeks, AZD6140 was administered (5mg/kg by gavage) and achieved sufficient plasma levels within 30 minutes. Platelet reactivity was determined by ADP-induced P-selectin expression, aggregation and adhesion on fibrinogen coated membranes under arterial flow conditions. RESULTS:At 0.5 hour, AZD6140 strongly reduced ADP-induced P-selectin surface expression, inhibited ADP-induced platelet aggregation, and significantly reduced platelet adhesion to fibrinogen under arterial flow conditions. Chronic treatment with AZD6140 (10mg/kg bid for 2 weeks, based on data obtained in the acute study) starting at day 14 reduced P-selectin surface expression on circulating platelets, indicating lower in vivo platelet activation. Platelet reactivity was improved 12 hours after the last dose, while basal platelet activity remained reduced. AZD6140 was rapidly absorbed in diabetic rats and inhibited platelet reactivity. Chronic treatment lowered in vivo platelet activation of circulating platelets. CONCLUSION:AZD6140 inhibits platelet reactivity in diabetic rats rapidly and reversibly. Markers of tonic platelet activation, which were increased in diabetic rats, were lowered to levels comparable to non-diabetic rats following chronic treatment with AZD6140.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Flierl U,Schöpp C,Jaitner J,Bauersachs J,Schäfer Adoi
10.1016/j.thromres.2009.09.025subject
Has Abstractpub_date
2010-03-01 00:00:00pages
e93-9issue
3eissn
0049-3848issn
1879-2472pii
S0049-3848(09)00418-6journal_volume
125pub_type
杂志文章abstract：:A direct assay for plasminogen activator (PA) was developed. It employed polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and beta-mercaptoethanol to monitor PA-mediated conversion of single chain, 125I-plasminogen to two chain plasmin. By incorporating Triton X-100, albumin and trasylol in...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(84)90008-2
更新日期：1984-05-01 00:00:00
abstract：:Pharmacovigilance is an essential element of any drug treatment and considering the history of adverse events due to products used to treat inherited bleeding disorders, it should be an integral component of modern haemophilia treatment. Because inherited bleeding disorders and adverse events are rare, a multicentre, ...
journal_title：Thrombosis research
pub_type： 杂志文章,多中心研究
doi：10.1016/S0049-3848(10)70150-X
更新日期：2011-01-01 00:00:00
abstract：INTRODUCTION:Ultrasound can accelerate clot dissolution in vitro and in vivo. We used an ex vivo canine shunt to investigate low frequency ultrasound effects on platelet-rich stent thrombosis. METHODS AND RESULTS:Nitinol stents were expanded to 2 mm in diameter in two perfusion chambers in a parallel shunt and exposed...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2003.10.023
更新日期：2003-01-01 00:00:00
abstract：:Analogs of the antithrombin peptide hirudin54-65 with C-terminal modifications have been synthesized in order to examine the requirements for alpha-thrombin inhibition. The C-terminal residue, Gln65, could be replaced with L-amino acids or amino alcohols with neutral or charged hydrophilic side chains without greatly ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90090-x
更新日期：1989-05-15 00:00:00
abstract：INTRODUCTION:Bivalirudin is an alternative to heparin anticoagulation in infants and children in the setting of extracorporeal life support (ECLS). While activated partial thromboplastin time (aPTT) is widely accepted as the standard test to monitor bivalirudin therapy, the usefulness of thromboelastometry (ROTEM) to m...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2019.12.007
更新日期：2020-02-01 00:00:00
abstract：INTRODUCTION:The activation of coagulation is recognized as a universal event in severe sepsis. Both antithrombin and thrombomodulin play pivotal roles as suppressors of coagulation. Since the levels of both anticoagulants decrease significantly, we hypothesized that a combination therapy would be beneficial. METHODS:...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.04.015
更新日期：2014-07-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.07.039
更新日期：2014-11-01 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
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(97)00267-3
更新日期：1997-11-15 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90065-9
更新日期：1985-02-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(01)00256-0
更新日期：2001-05-15 00:00:00
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journal_title：Thrombosis research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0049-3848(97)00062-5
更新日期：1997-05-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/s0049-3848(03)00336-0
更新日期：2003-05-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90102-3
更新日期：1989-02-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(93)90008-c
更新日期：1993-01-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2012.03.012
更新日期：2012-09-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/s0049-3848(01)00298-5
更新日期：2001-09-30 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2007.09.008
更新日期：2008-01-01 00:00:00
abstract：OBJECTIVES:To evaluate the role of filter implantation in reducing the incidence of fatal pulmonary embolism during the endovascular treatment of thrombosis in the major tributary of the superior vena cava (SVC). METHODS:From October 2004 to October 2008, we conducted a cohort study of 40 patients with thrombosis of t...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.04.009
更新日期：2014-07-01 00:00:00
abstract：:The specific thromboxane A2/prostaglandin H2 (TXA2/PGH2) antagonist 13-azaprostanoic acid (13-APA) reverses platelet aggregation stimulated by TXA2/PGH2 and the prostaglandin endoperoxide analog U46619. The present report demonstrates that the deaggregatory properties of 13-APA are potentiated by prostacyclin (PGI2). ...
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pub_type： 杂志文章
doi：10.1016/0049-3848(82)90097-4
更新日期：1982-12-15 00:00:00
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pub_type： 杂志文章,评审
doi：10.1016/S0049-3848(08)70003-3
更新日期：2008-01-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(84)90258-5
更新日期：1984-06-15 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(94)90201-1
更新日期：1994-11-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/S0049-3848(16)30100-1
更新日期：2016-04-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.10.006
更新日期：2013-01-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2005.12.019
更新日期：2007-01-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2012.04.009
更新日期：2012-09-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2011.02.004
更新日期：2011-06-01 00:00:00
abstract：:Soluble fibrin (SF) has attracted considerable interest as a marker for haemostatic activation. Two new enzyme immunoassays for SF, Enzymun-Test FM (Boehringer Mannheim, Germany) and Fibrinostika Soluble Fibrin (Organon Teknika, Belgium) have recently become commercially available. We measured plasma levels of SF in c...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(96)00036-9
更新日期：1996-03-15 00:00:00
abstract：:Studies with animal models implicate the plasma proteases factor XIIa (FXIIa) and α-kallikrein in arterial and venous thrombosis. As congenital deficiencies of factor XII (FXII) or prekallikrein (PK), the zymogens of FXIIa and α-kallikrein respectively, do not cause bleeding disorders, inhibition of these enzymes may ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2016.02.020
更新日期：2016-04-01 00:00:00
