Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variable antiplatelet effects have been described for various antianginal drugs, including beta-blockers, verapamil, and nifedipine. To assess and characterize a possible similar effect of nitrates, platelet-rich plasma (PRP) from 22 healthy donors was incubated with scalar concentrations (1.25, 12.5, 125 micrograms/ml) of isosorbide dinitrate (ISDN) and with the vehicle alone for periods of 5 and 10 min. Platelet aggregation was successively induced by ADP (0.4-1.2 microM), adrenaline (0.8-8 microM), collagen (16.7 micrograms/ml), arachidonic acid (AA; 1 mM) and thrombin (0.5-2 U/ml). At the end of aggregation thromboxane (TX) B2 levels in PRP were assessed by RIA. A dose-dependent decrease in both platelet aggregation and TXB2 levels by all the inducers tested was demonstrated with both incubation times. Maximum inhibition of platelet aggregation was observed with ADP and adrenaline (72.0% and 55.6% respectively with 10-min incubation and the highest ISDN concentration. P less than 0.01 and P less than 0.05 respectively). A reduction in TXB2 levels in PRP was also observed, but reached statistical significance (P less than 0.01) only for AA-induced TXB2 generation. For an in vivo study ISDN was infused for periods of 30 min at 4 mg/h in 11 angina patients, and for periods of 20 min at 30 mg/h in an other eight, under ECG and arterial blood pressure monitoring. ADP- and adrenaline-induced aggregation and TXB2 production, and determination of circulating platelet aggregates (CPA) were performed in basal conditions and at 5, 15, 30 and 90 min from infusion start in the first group, at 5, 15, and 80 min in the second group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiplatelet effects of isosorbide dinitrate in man. 666 33

Platelet 14C-serotonin release induced by collagen, and platelet malondialdehyde (M.D.A.) generation induced by thrombin were assessed in twenty patients with stable angina, before and after exercise with a bicycle ergometer. The patients received a single oral 200 mg dose of indobufen or placebo according to a crossover design in double-blind conditions. The M.D.A. concentration increased when exercise was carried out after placebo, whereas indobufen markedly inhibited M.D.A. production and 14C-serotonin release. These results suggest that effort may be an important factor in activation of the platelet prostaglandin pathway and that the use of antithrombotic drugs may be appropriate in patients with angina.
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PMID:Platelet release reaction and prostaglandin pathway activation in angina patients during exercise: effect of indobufen. 683 66

Although platelets have been associated with angina pectoris, myocardial infarction, and sudden death, the platelet's capacity for induction and propagation of cardiac ischemia remains incompletely defined. We therefore evaluated the effects of platelet activation occurring within the coronary circulation and tested the hypothesis that inhibition of platelet function would prevent platelet-induced cardiac ischemia. Human platelets were isolated from blood obtained from normal donors by Sepharose 2B column chromatography, resuspended in Hepes buffer, and added to the perfusate of a Langendorff rabbit heart (platelet counts greater than 10,000/microliters). Without, and with low dose (10 microM) prostaglandin E1 (PGE1), a reversible inhibitor of platelet function, immediate and irreversible global cardiac ischemia, as monitored by NADH fluorescent photography, ensued (N = 4) following platelet activation with thrombin (0.1 to 1 U/ml). Higher concentrations of PGE1 (0.1 to 1 mM, N = 2) or aspirin ingestion (1000 mg taken approximately 12, 4, and 1 hr prior to experiment, N = 2) completely prevented this platelet-induced myocardial ischemia. Aspirin, unlike PGE1, was effective despite its inability to block thrombin-induced platelet aggregation in our in vitro gel-filtered system. We conclude that activation of platelets within the coronary circulation is sufficient for induction of irreversible cardiac ischemia. The efficacy of aspirin, a cyclooxygenase inhibitor, further suggests that the products of arachidonate metabolism (e.g., thromboxanes) have a fundamental role in the genesis of platelet-mediated myocardial ischemia.
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PMID:Platelet-mediated cardiac ischemia. 713 26

Platelet function was studied during pacing-induced angina pectoris in nine patients with coronary heart disease. Blood was sampled via catheters from the coronary sinus and the aorta at rest and during angina. The influence of the sampling procedures on the platelet function was evaluated in blood collected via catheters and via short venflons. The catheter induced pseudopod formation in the platelets. The aggregation response was similar, while platelet retention as measured with Hellem's method for native blood, was slightly lower in blood collected via catheters than via venflons. At rest the maximal rate of primary, ADP-induced aggregation was lower in blood from the coronary sinus than from the aorta, as was the percentage of platelets retained in glass bead columns. The ability of platelets to produce prostaglandin metabolites, estimated from malondialdehyde formation after thrombin stimulation was also moderately, but significantly lower in coronary sinus blood. During pacing-induced angina primary, ADP-induced aggregation and platelet retention values remained significantly lower in blood that had passed the coronary circulation than the aortic blood. There were no differences between aortic or coronary sinus samples collected at rest than during pacing. Unchanged platelet counts indicates that trapping of platelets did not occur. Thus, platelet reactivity was lower in coronary sinus than aortic blood at rest in patients with coronary heart disease, and a moderate pacing-induced angina did not influence this pattern.
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PMID:Pacing induced angina and platelet reactivity. 716 26

A comparative study of activity of the progressively acting antithrombin and their heparin-cofactor activity was undertaken in 27 patients with angina pectoris and 46 with macrofocal myocardial infarction. It was established that the count of thrombin inactivation during 5 minutes (Abiligaard method) shows no disorders in the majority of patients. Only in 3 patients with the primary antithrombin III and 3 (40% of patients with acute myocardial infarction showed a marked decrease of this parameter. Inactivation count of the endogenous thrombin according to the "self-coagulogram" during one hour enabled one to show decrease of activity of antithrombin in of 80% of patients. The heparin-cofactor activity in the serial heparin-thrombin test is markedly disrupted, which was used to compute the indices of activity of antithrombin and of the antithrombin plasma reserve. This disorder did not depend much on the increase of the antiheparin factor of thrombocytes in plasma.
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PMID:[Progressively acting antithrombins and plasma heparin resistance in ischemic heart disease]. 728 82

Eighteen patients with an established angina pectoris aged 46-74 years were investigated. These patients received a low cholesterol, linoleic acid enriched diet during a period of three months. Of these patients seventeen terminated the three months period. The adherence to the diet was assessed by determining the fatty acid pattern in cholesterol and triglycerides. Both were found to increase significantly and to the same extend. When comparing the values between the entry to the study and after three months of dietetic intervention we found a significant improvement in the fibrinogen level, haematocrit, the aggregation of platelets, the PAT I test according to Breddin and in the test according to Wu and Hoak. However, the fibrinolytic activity before occlusion of an arm was disminished. The changes in ADP -, collagen -, adrenalin and thrombin induced platelet aggregation were not uniform. We found a significant lowering of VLDL, LDL, phospholipids and total cholesterol. HDL did not change significantly. It seems that the diet had a favourable effect on several thrombotic and lipoprotein parameters in these patients.
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PMID:Effect of low cholesterol, linoleic acid enriched diet on thrombotic tendency and plasma lipoproteins in patients with angina pectoris. 745 78

The degree of platelet activation and damage in 15 cases with acute myocardial infarction (AMI) receiving thrombolytic therapy and 15 cases with AMI receiving anticoagulant therapy were studied in vivo and in vitro by using specific monoclonal antibodies (SZ-51 & S12) against alpha-granule membrane protein 140 (GMP-140). Clinical indexes and myocardial enzyme changes in the two groups of patients were also observed. The results showed that the number of GMP-140 molecules on platelet surface and the concentration of GMP-140 in plasma were increased before treatment. The number of GMP-140 molecules on platelet surface began to decrease on the 1st day and returned to baseline on the 7th day after treatment. The concentration of GMP-140 in plasma reached a peak on the 1st day, began to fall on the 2nd day and returned to baseline on the 3rd day after treatment. There were no significant differences in the dynamic changes of number of GMP-140 molecules on platelet surface and the concentration of GMP-140 in plasma between groups of thrombolytic therapy and anticoagulant therapy. In vitro experiment showed that the thrombolytic medicine urokinase neither activated platelets nor inhibited platelet activation induced by thrombin. Significantly greater reperfusion rate and earlier appearance of CK and CK-MB peaks were found in the thrombolytic than in the anticoagulant group. LVEF determined by echocardiography, rate of return of ST segments to baseline and alleviation rate of chest pain were significantly greater and complications of AMI (ventricular fibrillation, left ventricular failure and angina) were less in the group receiving thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dynamic observation of alpha-granule membrane protein 140 during the treatment of thrombolytic and anticoagulant therapy in patients with acute myocardial infarction]. 758 6

The number of low density platelets was found to be increased in patients with hypercholesterolemia, as compared with the number in controls. The percentage increase of the low density platelet subpopulation was even more pronounced in patients with hypercholesterolemia when compared with that in patients suffering from myocardial infarction or angina. In vitro studies with control platelets incubated with cholesterol rich liposomes showed also an increase in the subpopulation of low density platelets. After incubation of control platelets with cholesterol rich liposomes, a higher membrane anisotropy and a higher cholesterol to phospholipid (C/P) molar ratio of the plasma membrane were found. Furthermore, cholesterol-enriched platelets were more sensitive upon thrombin stimulation. The results suggest that a shift of platelet subpopulations to a higher number of low density platelets could be caused by either the level of plasma cholesterol or an in-vitro incubation with cholesterol rich liposomes.
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PMID:Increased number of high sensitive platelets in hypercholesterolemia, cardiovascular diseases, and after incubation with cholesterol. 760 60

Ischemic electrocardiographic changes were recorded within 2 hours of admission using a 12-lead electrocardiographic continuous monitor with a 20-second scanning interval and an alarm mode for asymptomatic events. Blood samples were obtained at admission and at the moment of asymptomatic events (group A). In the other patients who did not develop ischemia, a second blood sample was taken 12 hours later (group B). We determined prothrombin time, activated partial thromboplastin time, clotting factor VIII activity, tissue plasminogen activator activity, tissue plasminogen activator inhibitor-1, cross-linked fibrin degradation product, and thrombin-antithrombin III complexes. There was a statistically significant difference between group A and B patients when the basal samples were analyzed for thrombin-antithrombin III (p = 0.046) and d-Dimer (p = 0.005). Prothrombin fragment 1 + 2 were significantly reduced, and d-Dimer was elevated when basal blood samples were compared with the second sample in patients who developed silent events (p = 0.008 and 0.055, respectively). A plasma concentration of thrombin-antithrombin III complex was also significantly decreased when sample 2 was compared with the basal blood sample (p = 0.039). Five recurrent episodes of angina and 2 nonfatal infarctions occurred, and 4 urgent revascularization procedures were performed in group A. In group B, there was only 1 nonfatal infarction (p = 0.01). The results of the present study suggest that a time-dependent thrombotic process is detectable in the blood stream as a cyclic movement. Further studies are needed to determine if some other factors, such as intensive shear stress in the vessel wall, may activate plaque instability during asymptomatic episodes.
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PMID:Time significance of acute thrombotic reactant markers in patients with and without silent myocardial ischemia and overt unstable angina pectoris. 761 Nov 44

Recombinant hirudin is currently being developed as a potential prophylactic and therapeutic antithrombotic drug in various clinical indications such as angina and deep venous thrombosis. In this report, we have discussed the production of specific polyclonal antibodies to recombinant hirudin (rH) and the development of two ELISA methods to measure rH concentrations in biological fluids: a sandwich and a competitive ELISA method. Intra- and inter-assay variations in the two methods are extremely low (3-7%). The competitive ELISA method is rapid, simple and highly reproducible. Saturation binding curves, selection of appropriate incubation times, recovery of different hirudin variants and reactivity in the presence of thrombin are discussed. The methods can be easily adapted to monitor hirudin concentrations in the clinical laboratory for diagnostic purposes as well as for performing pharmacokinetic studies.
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PMID:Development and validation of two enzyme-linked immunosorbent assay (ELISA) methods for recombinant hirudin. 766 Jan 41


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