Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study reports the correlation of the thrombin generation test and the plasma clot impedance test with clinical evidence of hypercoagulability. Thrombin generation is increased and the rate of change of plasma from a liquid to a gel (clot impedance) is increased in situations where the risk of thrombosis is increased. These situations include increasing clinical signs and/or symptoms of thromboembolism, positive lung scans, postoperative total hip replacement, patients over 40 years old, low serum antithrombin III, thrombocytosis, transient cerebral ischemia, and positive isotope venogram for thrombosis. The two tests failed to indicate a significant effect of antiplatelet drugs on the hypercoagulable state. This study shows that the thrombin generation and plasma clot impedance tests are practical, rapid and useful tests for the detection and monitoring of the hypercoagulable state.
 ...
PMID:Evaluation of the in vitro detection of the hypercoagulable state using the thrombin generation test and plasma clot impedance test. 50 79

Sneddon's syndrome is a rare condition comprising widespread livedo retucularis and multiple episodes of transient cerebral ischemia. Treatment to date has been empirical. The hemostatic/thrombotic status of 4 patients with Sneddon's syndrome was studied by a unique technique, hemostatometry, which measures primary hemostasis (shear-induced platelet plug formation), the overall coagulation, and thrombolysis (dislodgment of the hemostatic plugs) from nonanticoagulated blood. In all 4 patients, platelet reactivity, which shows itself in the initial phase of the hemostatic reaction, was enhanced. The overall hemostasis, in which the generation of thrombin by activated platelets plays the decisive role, was enhanced in 3 patients. Three of the 4 patients had hypercoagulation, and in 3, spontaneous thrombolysis was inhibited. Treatment was commenced with aspirin and nifedipine, and patients were monitored both clinically and by serial hemostatometry over two years. One patient had one further transient ischemic episode; the other 3 remained asymptomatic. Thus, the observed clinical improvement correlated with improvement of the hemostatic profile.
 ...
PMID:Hemostatic abnormalities in Sneddon's syndrome. 155 20

Acute myocardial infarction is most commonly initiated by fissuring of an atheromatous plaque. Through such fissures the blood is exposed to thrombogenic constituents of the intima, causing thrombotic obstruction of the coronary artery. Why plaque fissuring occurs is not known. Our investigation is to establish which types of plaque undergo fissuring by relating their mechanical with their cellular and biochemical properties; and to quantify the distribution of fissures. Results so far indicate that fissures occur predominantly in plaques with lipid pools in one segment of intima, and that the commonest single site of fissuring is that of maximal stress concentration as predicted by computer modelling. The results also suggest that arterial spasm at the immediate site of fissuring is not involved, as more than half the fissures occur at sites where there is no residual medial smooth muscle. Obstructive coronary thrombosis is initiated in most cases by plaque fissure with local haemorrhage which induces intravascular platelet aggregation. Recent observations with novel techniques have provided evidence that platelet aggregation in vivo is initiated by ADP and potentiated by thromboxane A2 and thrombin, with actual contribution of exposed collagen still undetermined. These observations provide an explanation for the limited effectiveness of any simple platelet-inhibiting drug, including Aspirin, by itself whenever arterial, eg. coronary or cerebral thrombosis is initiated by haemorrhages into atheromatous plaques. On the other hand, Aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Coronary thrombosis: pathogenesis and prevention. 210 21

We investigated hemostatic function in patients with cerebral ischemia by evaluating platelet activation, fibrin generation, and fibrinolysis. Plasma beta-thromboglobulin, an index of platelet activation, was significantly increased both acutely (14.9 +/- 9.2 ng/mL; n = 85) and approximately 2 months later (17.3 +/- 10.1 ng/mL; n = 57). Thrombin activity was measured using assays for fibrinopeptide A and fibrin D-dimer. Increased fibrinopeptide A was found in 9 (11.5%) of 78 patients acutely and 6 (10.7%) of 56 at follow-up; fibrin D-dimer levels were significantly increased acutely (166 +/- 188 ng/mL; n = 66) but not at follow-up. Fibrinolytic activity was measured using assays for fibrinopeptide B-beta 1-42 and plasminogen activator inhibitor 1. Fibrinopeptide B-beta 1-42 was significantly reduced acutely (6.3 +/- 2.2 pmol/mL; n = 35) and at follow-up (4.8 +/- 1.5 pmol/mL; n = 21). Plasminogen activator inhibitor 1 was normal acutely (20.1 +/- 12.0 ng/mL; n = 73) but increased at follow-up (27.8 +/- 20.1 ng/mL; n = 45). These results demonstrate that patients with cerebral ischemia have abnormal hemostatic function that is not explained by the acute phase reaction, and that components of the prethrombotic state are present in some of these patients.
 ...
PMID:Altered coagulation in cerebral ischemia. Platelet, thrombin, and plasmin activity. 214 26

TA-3090 (8-chloro diltiazem) has been shown in three experimental circumstances to have cerebrovascular protective properties. In vitro investigation of its pharmacology was undertaken to determine the foundation of this effect. Based on contractile responses of rabbit arteries to high potassium and norepinephrine, TA-3090 has some selectivity for cerebral and renal artery potential-sensitive and cerebral receptor-operated calcium-dependent mechanisms. It has no effect on arterial contraction to sympathetic nerve stimulation. It prevents the increase in uptake of 45Ca2+ in response to K+ (80 mM) in rabbit thoracic aorta and antagonizes the contractile effect of the putative cerebrovascular spasmogen alpha-thrombin on the femoral artery. All these effects take place in concentrations below those that significantly depress the action of the rabbit atrium. TA-3090 has little or no effect on other factors known to regulate cerebral blood flow (e.g., stretch-induced contraction and flow-induced contraction and dilation). This spectrum of pharmacologic activity suggests that TA-3090 would selectively block Ca2+ entry into cerebrovascular smooth muscle through potential-sensitive and receptor-operated Ca2+ channels that would be expected to increase in subarachnoid hemorrhage and cerebral ischemia. The action would occur using doses that have little effect on other factors that contribute to the control of cerebral blood flow.
 ...
PMID:Pharmacology of TA-3090 (8-chloro diltiazem) related to its cerebrovascular protective properties. 259 53

Nimodipine is a new calcium antagonist that has been advocated as a specific treatment for the cerebral vasospasm accompanying subarachnoid hemorrhage in humans because of reports that it selectively inhibits the constriction of cerebral arteries in vitro. Because calcium antagonists may have specific blocking actions, whereas the origin of vasospasm is likely to be multiplex, the effect of nimodipine on the contractions of isolated canine basilar arteries that are produced by serotonin, prostaglandin F2 alpha, thrombin, and whole blood was studied. The results demonstrate that nimodipine significantly inhibits the contractile responses induced by these diverse agonists whether it is given before or after the agonist. The findings suggest that, in canine cerebral arteries, a common calcium influx channel is involved in the responses elicited by a variety of receptor mechanisms and afford a rationale for the use of nimodipine in the treatment of the cerebral ischemia that often follows cerebral hemorrhage.
 ...
PMID:Effect of the calcium antagonist nimodipine on contractile responses of isolated canine basilar arteries induced by serotonin, prostaglandin F2 alpha, thrombin, and whole blood. 695 Nov 13

The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Antithrombotic agents in cerebral ischemia. 786 71

Platelet-dependent thrombosis and subsequent embolization are major causes of cerebral ischaemia. Beside aspirin which irreversibly blocks platelet cyclo-oxygenase, several other substances interfere in different platelet metabolic pathways and block platelet adhesion and aggregation. We found in an experimental model using non-human primates that a specific peptide inhibitor blocking GP IIb/IIIa platelet receptor which binds fibrinogen completely, prevents the retention of embolized platelet aggregates in the cerebral circulation. As thrombin may play a key role for platelet activation in vivo leech-derived hirudin, a direct thrombin inhibitor as well as activated protein C which limits thrombin production and also prevents platelet dependent thrombus formation very effective. We demonstrated in the same non-human primate model of platelet embolization that the amount of retention of platelet emboli in the vascular bed depends on the nature of the vasculature. For example, platelet emboli were cleared very quickly from brain microcirculation, whereas platelet embolization into the lower limb via the femoral artery caused a significantly longer retention of the embolized material. Such specific mechanisms may be caused by different levels of local vasodilators as PGI2 or EDRF.
 ...
PMID:Platelet thromboembolism. 801 31

To elucidate the role of thrombin in brain damage during focal cerebral ischemia, we investigated the effects of a selective thrombin inhibitor, argatroban, on microthrombi formation, regional cerebral blood flow (rCBF), infarct areas and neurological deficits using a rat thrombotic distal middle cerebral artery (dMCA) occlusion model. The rat dMCA was occluded by a platelet-rich thrombus formed after photochemical reaction between rose bengal and green light. One day after dMCA occlusion, the number of microthrombi were counted. In the separate animals, rCBF was measured by using the iodoantipyrine method 1 day after dMCA occlusion. Three days after dMCA occlusion, behavioral tests were performed and the size of the cerebral infarction was determined. In the present study, argatroban was administered i.p. by continuous infusion after dMCA occlusion. Argatroban (0.3 mg/h/rat) significantly (P < .05) decreased the number of microthrombi 1 day after dMCA occlusion. Argatroban (0.1 and 0.3 mg/h/rat) significantly (P < .01) reversed a decrease in rCBF 1 day after dMCA occlusion. Argatroban (0.3 mg/h/rat) also significantly (P < .01) reduced the size of the cerebral infarction. Administration of argatroban (0.1 and 0.3 mg/h/rat) resulted in a significant improvement in neurological deficits 3 days after dMCA occlusion (P < .01 and P < .05, respectively). Argatroban decreased the size of the cerebral infarction and improved neurological deficits in the rat thrombotic dMCA occlusion model. These effects were thought to be due to the improvement of rCBF and to the reduction in secondary thrombus formation after dMCA occlusion.
 ...
PMID:Effects of a thrombin inhibitor, argatroban, on ischemic brain damage in the rat distal middle cerebral artery occlusion model. 876 31

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-alpha, IL-1-alpha and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-alpha, IL-1-alpha) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.
 ...
PMID:Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain. 889 62


1 2 3 4 5 6 7 Next >>