Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From injury through healing, thrombin has several important functions in blood clotting, subsequent clot lysis, and tissue repair. These include edema, inflammation, cell recruitment, cellular releases, transformations, mitogenesis, and angiogenesis. Thrombin also participates in disease states, such as venous thrombosis, coronary thrombosis, stroke, and pulmonary emboli, among others and is implicated in atherosclerosis, the growth and metastasis of certain cancers, Alzheimer's disease, and perhaps other conditions. Thrombin must be continually generated to sustain normal and pathogenic processes. This is because of a variety of consumptive mechanisms. Unlike other activated factors in thrombotic and fibrinolytic pathways, and because thrombin promotes its own generation (feedback and cellular activation), thrombin is a primary target for therapeutics. Besides recombinant hirudins, Argatroban (Novastan) and Bivalirudin (Hirulog) are promising thrombin-directed inhibitors for antithrombotic intervention.
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PMID:Thrombin and antithrombotics. 957 30

Worldwide, streptokinase continues to be used widely in the treatment of myocardial infarction because it is inexpensive and causes fewer intracranial hemorrhages than other thrombolytic regimens. However, in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-I) trial, the 90-minute angiographic Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow rate with streptokinase was 43% lower than that with accelerated tissue plasminogen activator, and there was a higher incidence of death or disabling stroke with streptokinase (7.8% vs 6.9%, p <0.01). In the first Hirulog and Early Reperfusion/Occlusion (HERO-1) trial, 48% of patients given the direct thrombin inhibitor bivalirudin (formerly Hirulog, The Medicines Company) after streptokinase had TIMI 3 patency at 90 minutes, compared with 35% of patients given intravenous heparin (p <0.05). Other angiographic and clinical studies and animal research have shown that early infarct artery blood flow may be increased markedly if a direct thrombin inhibitor is administered before the thrombolytic agent. In the HERO-2 trial, 17,000 patients presenting within 6 hours after the onset of acute myocardial infarction will be given aspirin and randomized to receive either intravenous heparin or bivalirudin before streptokinase is administered. The primary endpoint will be 30-day mortality, and secondary endpoints will include death or myocardial infarction within 30 days, and death or nonfatal disabling stroke. If the thrombin hypothesis is supported by improved clinical outcomes with bivalirudin in the HERO-2 trial, large-scale clinical trials will be needed to evaluate the administration of direct thrombin inhibitors before other thrombolytic regimens.
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PMID:Direct thrombin inhibition and thrombolytic therapy: rationale for the Hirulog and Early Reperfusion/Occlusion (HERO-2) trial. 980 93

Hirulog-like peptide (HLP) and low-molecular-weight heparin (LMWH) are thrombin inhibitor peptides. Our previous study demonstrated that HLP could reduce vascular neointimal formation or restenosis in animals undergoing balloon catheter injury in the carotid artery. However, the function of HLP during ischemic stroke is largely unknown. The present study investigated the effect of HLP on brain injury, which was induced by suture of middle cerebral artery occlusion in mice. Mice were divided into four groups, which included a sham group and three treatment groups. Ischemia was induced by transient suture insertion into the middle cerebral artery for 90 min, and mice were either treated with saline, HLP or LMWH. Infarct volume, neurologic deficits and apoptotic factors were measured following 1-14 days of ischemia. We demonstrated that HLP intravenous injection alleviated brain infarct volume and improved neurologic outcomes (p<0.05). HLP decreased levels of protease-activated receptor-1 (PAR-1), caspase-3, malondialdehyde (MDA) and Bcl-2-associated X protein (Bax), increased the activities of catalase and B cell lymphoma-2 (Bcl-2), and improved the ratio of Bcl-2/Bax compared with the control (p<0.05). This study indicates that HLP and LMWH reduced infarct volume and improved neurobehavioral outcomes induced by transient middle cerebral artery occlusion (tMCAO). In addition, HLP had a beneficial effect on the regulation of the thrombin receptor and key apoptosis regulators in the mouse brain. These results suggest that HLP may be a potential alternative therapy for arterial occlusion-induced cerebral ischemia.
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PMID:Effect of hirulog-like peptide on middle cerebral artery occlusion-induced brain injury in mice. 2506 24