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)

Genetic risk factors play an important role in the aetiology of vascular diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an increased risk of myocardial infarction. We investigated 136 patients with minor stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0.32 for the 4G/4G genotype in patients compared with 0.42 in 115 age-matched healthy controls. The 4G/4G genotype was significantly less frequent among 61 patients symptomatic before the age of 60 years (prevalence 0.20) than in 75 patients symptomatic after 60 years of age (prevalence 0.42; odds ratio). Our results indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even be protective in young patients.
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PMID:The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls. 1097 10

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.
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PMID:Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids. 1109 67

Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p<0.001). tPA concentrations were not different among groups (p=0.89). PAI-I levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications.
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PMID:Plasma levels of coagulation and fibrinolysis markers in acute ischemic stroke patients with lone atrial fibrillation. 1121 63

This paper aimed to investigate the effect of lumbrokinase on the anticoagulation and fibrinolysis in treating cerebral infarction. Lumbrokinase was used in patients with cerebral infarction. Patients were randomly divided into treatment group (n = 31) and control group (n = 20). Single blind method was used in this investigation. The Chinese stroke score was used to evaluate the results of treatment before and after administration of lumbrokinase. Kaolin partial thromboplastin time (KPTT), prothrombin time (PT), fibrinogen content, vWF content were analyzed, and tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI) activity, D-dimer level were assayed. In both groups, the stroke score decreased after administration, but in the treatment group, it was more obvious. In the treatment group, KPTT was prolonged, t-PA activity and D-dimer level increased, while the content of fibrinogen decreased significantly. There were no significant changes of PT and PAI activity in both groups. It is concluded that lumbrokinase is beneficial to the treatment of cerebral infarction. The effect of lumbrokinase is related to the inhibition of intrinsic coagulation pathway and the activation of fibrinolysis via an increase of t-PA activity.
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PMID:Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. 1132 42

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
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PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.
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PMID:Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project. 1146 15

Information is lacking regarding dynamic platelet accumulation at the site of the occluded middle cerebral artery (MCA) and the relationship between platelet aggregation in downstream cerebral microvessels and loss of perfusion and vascular integrity of these microvessels. In the present study, we employed a model of embolic MCA occlusion in the rat to simultaneously measure temporal and spatial profiles of platelet accumulation at the site of the embolus occluding the MCA and within downstream cerebral microvessels. We also measured the integrity of microvessels and matrix metalloproteinase (MMP) activity in ischemic brain. Rats (n=36) were subjected to embolic MCA occlusion. Immunohistochemistry was used to detect microvascular integrity, plasminogen activator inhibitor 1 (PAI-1) and the deposition of fibrin. SDS-PAGE zymography was used to measure MMP2 and MMP9 activities. Accumulation of platelets and increases in PAI-1 immunoreactivity at the site of the embolus occluding the MCA were detected 1 h (n=7) and 4 h (n=7) after ischemia, respectively, and numbers of GPIIb/IIIa immunoreactive downstream cerebral microvessels increased significantly (209+/-59; n=7; P<0.05) 4 h after ischemia, suggesting dynamic platelet aggregation. A significant (n=7; P<0.01) diffuse loss of type IV collagen immunoreactivity in microvessels was temporally associated with platelet GPIIb/IIIa immunoreactivity within the vessels. Triple immunostaining revealed that microvessels containing platelet aggregates exhibited loss of type IV collagen immunoreactivity and both intra- and extra-vascular fibrin deposition, suggesting that intravascular platelet aggregation is associated with decreases in the integrity of the microvascular basal lamina and blood-brain barrier leakage. A significant increase (P<0.05) in MMP9 was detected at 4 h (n=3) and 24 h (n=3) after ischemia but levels of MMP2 were not significantly changed in ischemic brain. Our data suggest that dynamic platelet aggregation in ischemic brain may contribute to time-dependent resistance to fibrinolysis. In addition, platelet deposition and increased MMP9 coincided with degradation of type IV collagen and loss of vascular integrity. These data suggest an important role for post-occlusive distal platelet deposition in the pathophysiology of stroke.
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PMID:Dynamic platelet accumulation at the site of the occluded middle cerebral artery and in downstream microvessels is associated with loss of microvascular integrity after embolic middle cerebral artery occlusion. 1153 35

To investigate the role of active plasminogen activator inhibitor 1 (PAI-1) in the evolution of a microthrombus generated in the arteriolar microcirculation, the monoclonal antibody, 33H1F7, which transforms active PAI-1 to a tissue type plasminogen activator (t-PA) substrate, was evaluated in an arteriolar thrombosis model in the rat mesentery. Arterioles (200-300 um) were stimulated electrically to create an endothelial lesion; ADP was then perfused for 2 min to induce the formation of a platelet-rich thrombus which lysed spontaneously in 140 +/- 24 s. Two successive ADP superfusions produced comparable thrombi which lysed in comparable times. Different doses of 33H1F7 were infused to rats for 30 min and the dose which inactivates rapidly and totally active rat PAI-1 (300 microg/kg/min) was selected to be tested on the thrombosis model. Infusion of 33H I F7 beginning 10 min before the ADP application significantly reduced the lysis time in comparison to the control (123 +/- 30 s versus 169 +/- 33 s, P < 0.05, paired Student's t-test) and the cumulative thrombus area during the lysis period was decreased by 56 +/- 7%. These results demonstrate that inactivation of PAI-1 is able to accelerate lysis of a platelet-rich clot in a mesenteric arteriole of the rat. Thus active PAI-1 most likely participates to the resistance to thrombolysis in the arteriolar microcirculation and its inactivation may shorten ischemic periods after microvascular obstruction such as e.g. during cerebral stroke.
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PMID:Inactivation of plasminogen activator inhibitor-1 accelerates thrombolysis of a platelet-rich thrombus in rat mesenteric arterioles. 1177 23

Although the incidence of strokes is not maximal during sleeping hours, several lines of evidence make it probable that sleep in combination with breathing disorders like snoring and obstructive apneas are risk factors for ischemic strokes: the natural history of snoring and obstructive sleep apnea shows a higher incidence of strokes than in undisturbed sleep, the prevalence of snoring and sleep apneas in stroke patients is by far higher than in non-stroke patients; odds-ratios of stroke are higher in snorers and apneic patients than in normals, although the correction for confounders seems never perfect. The analysis of potential pathomechanisms linking sleep disordered breathing to strokes is another approach to the main topic: snoring and sleep apnea induce hypertension and arrhythmia, the carotid intima-media-thickness is increased, carotid atheromas are more common among apneics than among normals, the flow in the A. cerebri media is as well altered as the reaction to angiotensine II, noradrensine, isoproterenol and bradykinin. Homocysteine is increased, plasminogen activator inhibitor type 1 is inhibited and platelets are activated leading to an increased risk of thrombosis. There are no studies showing the effectiveness of treatment with nasal continuous positive airway pressure (nCPAP) on the rehabilitation of apneic stroke patients, but the outcome of non-apneic stroke patients is better than that of apneic stroke patients.
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PMID:Sleep and stroke. 1192 38

Elevated levels of tissue-type plasminogen activator antigen (tPA), fibrinogen, and fibrin D-dimer predict coronary artery disease (CAD) events and stroke. These factors, possibly in association with insulin resistance, may be important in families in which CAD has become clinically apparent at a premature age. From 125 patients with angiographically confirmed, premature CAD, 175 healthy male relatives (age </=65 years) were identified. One hundred seventy-five healthy volunteers of similar age and without any family history of CAD were recruited. There were no differences between relatives and controls in terms of conventional CAD risk factors, cigarette smoking, alcohol consumption, or cardiorespiratory fitness. Estimated insulin resistance and plasminogen activator inhibitor 1 levels were not increased in relatives. Fibrin D-dimer, tPA, and fibrinogen levels were elevated in relatives compared with controls, 55 (52 to 58) ng/mL versus 49 (45 to 53) ng/mL, P<0.01, for D-dimer; 8.0 (7.5 to 8.6) ng/mL versus 5.6 (5.2 to 6.1) ng/mL, P<0.001, for tPA; and 3.0 (2.9 to 3.1) g/L versus 2.8 (2.7 to 2.9) g/L, P<0.05, for fibrinogen. These differences remained after adjustment for correlates, including fibrinogen, age for D-dimer, and features of the insulin resistance syndrome for tPA. tPA and D-dimer levels are elevated in the healthy, male, first-degree relatives of patients with premature CAD. This association is independent of potential confounding factors.
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PMID:Tissue plasminogen activator, fibrin D-dimer, and insulin resistance in the relatives of patients with premature coronary artery disease. 1195 Jul 14


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