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)

Using strips of human basilar arteries mounted in organ chambers to record isometric tension, we investigated vascular reactivity to thrombin and bradykinin. Both agents produced endothelium-dependent relaxation of basilar artery strips precontracted with phenylephrine but had no effect on resting tension in strips with or without endothelium. The relaxations caused by thrombin were abolished by antithrombin III/heparin, hirudin, and MD805. Thrombin but not bradykinin caused complete tachyphylaxis toward a second exposure. Indomethacin did not inhibit the relaxations induced by thrombin or bradykinin, whereas bromophenacyl bromide and methylene blue did. Aging decreased the relaxation induced by thrombin but did not affect the concentration needed to reach 50% maximal relaxation, nor did it affect the maximal relaxation in response to bradykinin, calcium ionophore A23187, and sodium nitroprusside. Our results suggest that thrombin and bradykinin produce endothelium-dependent relaxations mediated by an endothelium-derived relaxing substance and that the relaxation caused by thrombin is mediated by a proteolytic action on endothelial cells. The decrease in relaxations in response to thrombin with increasing age might be due to a decrease in the number or sensitivity of thrombin receptors on endothelial cells.
Stroke 1990 Jul
PMID:Effect of aging on endothelium-dependent vascular relaxation of isolated human basilar artery to thrombin and bradykinin. 211 73

Ten clinically healthy subjects (5 men and 5 women), 31 +/- 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.
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PMID:Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. 212 46

Using two-dimensional echocardiography, we studied the pathophysiology of intracardiac thrombus regression accompanied by anticoagulant therapy in 82 consecutive patients with acute cardiogenic cerebral embolism. We noted intracardiac thrombus in 15 patients; nine of the 15 were started on anticoagulant therapy with warfarin potassium to maintain the prothrombin time between 2.5 and 3.5 (international normalized ratio). Serial two-dimensional echocardiograms were obtained for these nine patients before and after anticoagulation, with the plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, and D-dimer measured at the same time. In eight of the nine patients the intracardiac thrombi gradually decreased in size while the plasma level of fibrinopeptide A fell to within the normal range and the plasma levels of fibrinopeptide B beta 15-42 and D-dimer remained above the normal ranges. In the other patient the thrombus disappeared, with embolization to the right arm immediately after starting anticoagulant therapy. Mobile or small thrombi regressed earlier than nonmobile or large ones. We conclude that regression of intracardiac thrombi after anticoagulation may be based on the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin activity.
Stroke 1990 Nov
PMID:Regression of intracardiac thrombus after embolic stroke. 223 46

Platelet activation results in the formation of various vasoactive mediators such as thromboxane A2 and serotonin. We investigated the effects of Bay U 3405 [(3R)-3- (4-fluorophenyl-sulfonamido)-1,2,3,4,-tetrahydro-9-carbazolepro panoic acid] on vasocontractions of isolated bovine cerebral arteries induced by U 46.619, a stable thromboxane/prostaglandin-endoperoxide analogue, and authentic thromboxane A2 released from thrombin-stimulated human platelets. Bay U 3405 (0.001-10 mumol/l) potently inhibited the contraction induced by U 46.619 and demonstrated a reduction of the thromboxane-mediated component of platelet-induced contractile response at higher concentrations (0.1-10 mumol).
Stroke 1990 Dec
PMID:Bay U 3405 inhibits cerebral vasospasm induced by authentic thromboxane A2. 226 Jan 41

Blood proteins could play a critical role in the pathogenesis of cerebral vasospasm in subarachnoid hemorrhage (SAH) as agonists and as antagonists of vasoconstriction. The present study was designed primarily to quantify the inhibition produced by antithrombin III of the phasic responses elicited by cumulative doses of KCl, serotonin (5-HT), uridine triphosphate (UTP), and thrombin in isolated canine basilar arteries, and to ascertain whether other proteins might act similarly. Antithrombin III (1 unit/ml and 3 units/ml) given 2 min beforehand inhibited all agonists. The inhibition was not dependent on a functional endothelium nor due to stimulation of the electrogenic sodium pump. Alpha2-macroglobulin (0.1 mg/ml and 0.4 mg/ml) inhibited the contractile responses to high K+, 5-HT and thrombin. Kallikrein (1 and 4 units/ml) did not inhibit UTP but inhibited high K+ and 5-HT through an effect on the endothelium. Kallikrein (1 unit/ml) irreversibly blocked the responses to thrombin. Globulins (3 mg/ml) and fibrinogen (0.3 mg/ml) were not inhibitory. The results demonstrate that anticoagulant proteins are very effective nonspecific inhibitors of the vasoconstriction, whereas the serine protease kallikrein selectively blocks thrombin. The remarkable potency of antithrombin III suggests that it may protect cerebral arteries from exhibiting vasospasm in SAH.
Stroke
PMID:Vasodilator proteins: role in delayed cerebral vasospasm. 242 60

Tissue plasminogen activator (tPA) dissolves intravascular thrombus and restores blood flow after thromboembolic vascular occlusion. The utility of this agent for treatment of stroke in humans may be limited by post-reperfusion hemorrhagic complications. We studied tPA-mediated thrombolysis in an animal model of cerebrovascular occlusion in order to determine what factors, if any, predispose tPA-treated animals to suffer hemorrhage. Small blood clot emboli were injected into the internal carotid arteries of rabbits. Angiograms confirmed occlusion of the middle cerebral artery or internal carotid artery in 100% of subjects. tPA or saline was administered as a 30-minute infusion at various times after embolization. Hemorrhage rates were similar in all groups regardless of treatment. tPA increased the prothrombin time and the thrombin time but not the partial thromboplastin time. There was no correlation between these changes in blood coagulation and the finding of cerebral hemorrhage. We observed a significant association between stroke severity and cerebral hemorrhage. We conclude that tPA treatment successfully causes thrombolysis of cerebral emboli without causing an increase in the incidence of cerebral hemorrhage in rabbits.
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PMID:Tissue plasminogen activator-mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits. 249 32

The mechanism of platelet dysfunctions in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. Platelet aggregation was inversely correlated with blood pressure or heart weight/body weight ratios in various strains of spontaneously hypertensive rats (SHR), indicating genetic defects. Thrombin-induced 47 kDa protein phosphorylation was markedly reduced in platelets of SHRSP compared with that in Wistar-Kyoto (WKY) rat platelets, accompanying reduced aggregation and secretion, but in 20 kDa protein phosphorylation was unchanged. Ca2+ ionophore A23187-induced responses were also significantly decreased in SHRSP, and the degrees of the changes were greater than those by thrombin. However, 12-O-tetradecanoylphorbol 13-acetate-induced responses in SHRSP were similar to those in WKY rats, suggesting that protein kinase C activity and its substrate were normally present in SHRSP platelets. Phosphatidylinositol content in platelets of SHRSP was 20% less than that in WKY rat platelets, but the contents of other phospholipids, including phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphates, were unaltered. Thrombin-induced formation of diacylglycerols and phosphatidic acid did not differ from each other at the low concentrations. In the absence of Ca2+, thrombin-induced responses occurred to a similar degree in both platelets, whereas the enhancements by Ca2+ were much greater in WKY rats than in SHRSP. These results suggested that defective Ca2+ functions in receptor-mediated activation of protein kinase C and postkinase-mediated events appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.
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PMID:Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets. 250 71

Plasma B beta 15-42 and fibrinopeptide A (FPA) concentrations, which are respectively indicators of plasmin and thrombin in vivo activity, were measured in 46 patients with ischemic arterial disease without signs of acute thrombosis. In the group as a whole, an increase in both B beta 15-42 and FPA was found. When the patients were divided in two groups on the basis of their reversible (transitory ischemic attacks and unstable angina) or irreversible (stroke and myocardial infarction) ischemic episodes, the levels of B beta 15-42 were significantly elevated only in the former group when compared to controls (p less than 0.01). In the latter group we found significantly increased levels of FPA with respect to both controls (p less than 0.01) and patients with reversible and transient ischemic episodes (p less than 0.05). Moreover, the B beta 15-42/FPA ratio was significantly lower in patients with irreversible ischemic episodes than in controls (p less than 0.01) and patients with transient ischemic episodes (p less than 0.01), while no difference was found between the latter group and controls, although FPA and B beta 15-42 were significantly higher. These results suggest that in patients with transient and reversible ischemic episodes fibrinolytic activity is able to counterbalance an increased thrombin activity, while this does not appear to occur in patients with irreversible ischemic episodes.
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PMID:Subclinical activation of fibrinolysis in atherosclerotic disease detected by B beta 15-42 assay. 252 2

To study the pathogenesis of platelet activation in ischemic stroke, ionized calcium ([Cai2+]) was measured in aequorin-loaded gel-filtered platelets in the basal and stimulated state. Basal [Cai2+] was increased in stroke patients maximally 36-72 hours after onset. The increase in [Cai2+] after stimulation with thrombin, collagen, and platelet-activating factor were also greater in stroke patients, but the profiles of these [Cai2+] changes were parallel to control. Cross incubation of control platelets with plasma from stroke patients resulted in raised basal [Cai2+] and caused the release of serotonin from platelets. These results indicate that the higher platelet basal [Cai2+] in stroke patients represents a lowered threshold for activation and that this may be due to a plasmatic factor rather than a primary platelet defect.
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PMID:A plasmatic factor may cause platelet activation in acute ischemic stroke. 258 96

Thromboembolic events play a major pathogenetic role in the final occlusion of atherosclerotic vessels. May such a catastrophic event be predicted or an increased risk be indicated by analyzing the hemostatic system in plasma? A hugh literature exists about disturbances of the platelet, coagulation and fibrinolytic systems after atherosclerotic events such as myocardial infarction or stroke. This data, however, has no predictive significance. In contrast, the epidemiological studies in healthy persons have shown fibrinogen to be a potent risk predictor which is independent from other risk factors such as age, cholesterol or cigarette smoking. Results on factor VII:C are still controversial. Ongoing studies have included further factors of the hemostatic system. A second approach to elaborate the predictive power of hemostatic factors is to follow up patients with overt atherosclerotic disease and to correlate baseline hemostatic tests with event recurrences. The ECAT Angina Pectoris Study performed in 19 European clinical centers will present its prospective results by 1990. Some correlations of risk factors at baseline point to the many interrelationships among each other and to the need of careful statistical management of such data. It is reasonable to include fibrinogen in the recently developed coronary risk scores. So far, thrombin clotting time procedures, such as the Clauss method, appear to be appropriate for the purposes of risk prediction.
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PMID:Predictive value of factors of the hemostatic system in screening procedures for coronary artery disease. 263 1


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