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)

A subgroup of children with arterial ischemic stroke in the pre- or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after two months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); six of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in five, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.
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PMID:Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. 1150 98

An emerging body of evidence indicates that beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or 'statins', provide neuroprotection in addition to reducing ischaemic stroke. Statins reduce the incidence of ischaemic stroke by stabilising atherosclerotic plaques in the precerebral vasculature and through antithrombotic actions, and the neuroprotective effects of statins may confer significant clinical benefit. Some of these neuroprotective effects are likely to be cholesterol independent and mediated by the interruption of isoprenoid biosynthesis. Therapy with statins may modulate endothelial function and preserve blood flow to regions exposed to an ischaemic insult. In particular, statin-mediated preservation of endothelial nitric oxide synthase activity in cerebral vasculature, especially in the ischaemic penumbra, may limit neurological deficit. Moreover, putative anti-inflammatory and antioxidant properties of statins may confer additional neuroprotection. Further large clinical trials are necessary to address the role of statin therapy in the primary prevention of stroke, small vessel cerebrovascular disease and vascular dementia.
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PMID:Do statins afford neuroprotection in patients with cerebral ischaemia and stroke? 1152 31

Proper therapy for patients with internal carotid artery stenosis requires a precise pathophysiologic diagnosis that includes characterization and localization of ischemic disease of the brain and knowledge of the arterial disease and the collateral cerebral circulation. Noninvasive techniques such as duplex ultrasound and transcranial Doppler, magnetic resonance angiography, and CT angiography allow precise determination of the stroke subtype and parent arterial pathology. Antiplatelet agents prevent the formation of thrombus on carotid artery atherosclerotic plaque. 3-Hydroxy-3-methyglutaryl coenzyme A reductase inhibitors may help stabilize carotid plaques by altering the plaque morphology and reducing inflammation. Carotid endarterectomy, which is the only procedure proven to be beneficial for patients with asymptomatic disease, should be considered primary intervention. Until ongoing trials for interventional procedures are completed, carotid artery angioplasty and stenting should be considered only in patients with contraindications to carotid endarterectomy. It can be argued that an ideal clinical trial in a high-risk population has not yet been completed. This factor has become even more important with the development of stenting procedures. We have long advocated a trial of only treating patients with hemodynamically significant stenotic lesions (70% to 99%).
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PMID:Asymptomatic Internal Carotid Artery Origin Stenosis. 1152 25

We describe a 36-year-old man with familial protein S deficiency and homozygosity to the methylene tetrahydrofolate reductase (MTHFR) thermolabile variant who had a stroke followed by an episode of idiopathic osteonecrosis that was successfully managed by surgical core decompression. The patient's symptomatic thrombophilia, as well as that of several of his first-degree relatives who also had thrombotic events, raises the possibility that the thrombophilia was a contributing factor to the development of his osteonecrosis.
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PMID:Idiopathic osteonecrosis in an adult with familial protein S deficiency and hyperhomocysteinemia. 1168 42

The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia.
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PMID:Statins and neuroprotection. 1177 90

It is becoming increasingly recognized that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors (statins) on reducing clinically important cardiovascular events (myocardial infarction and stroke) are not only attributable to their hypocholesterolemic effect but also to non-lipid mechanisms of action. The nonlipid factors may include the stabilization of arterial plaques, endothelial normalization, anti-inflammatory effects and inhibition of platelet thrombus formation. The inhibition of platelet thrombus formation has not been adequately studied in man and the results are often contradictory. It is the objective of this review to discuss the effects of statins on platelet aggregation in the context of relatively new and specific techniques for the measurement of platelet function as reported by Ma and coinvestigators in this issue of JAAMP. Ma et al. examined the effect of pravastatin given for 8 to 12 weeks on platelet function and low density lipoprotein-cholesterol (LDL-C) in 21 Chinese patients with primary hypercholesterolemia. Platelet function was evaluated by adenosine diphosphate (ADP)-induced aggregation, thromboxane B2 (TXB2) and the expression of alpha granule membrane protein-140 (GMP-140). GMP-140 is considered one of the most sensitive indicators of the state of platelet function. As expected, pravastatin treatment significantly reduced LDL-C and inhibited ADP-induced platelet aggregation, TXB2 synthesis and the expression of GMP-140--all such parameters can lead to thrombus formation and subsequent cardiovascular events. Using the test methods of Ma et al., additional dose-response studies with several statins and standard antiplatelet drugs are needed to confirm their effects on platelet aggregation, if any. Furthermore, we need to determine whether the antiplatelet effect of the statins, if present, is independent of their hypocholesterolemic action. The additional studies could provide important clues toward the development of new and specific antithrombotic drugs.
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PMID:Statins, platelet aggregation and coronary heart disease. 1185 68

Inflammation-related processes play a key role the current etiologic model of atherosclerosis and its acute complications. Recent evidence suggests that blood-based biomarkers that reflect systemic inflammation may contribute to our ability to predict future risk of cardiovascular disease. Global markers of inflammation, such as C-reactive protein and fibrinogen, have been well studied as potential cardiovascular risk factors. A variety of additional markers that reflect various elements of the complex systems governing inflammation, including proinflammatory and antiinflammatory cytokines, mediators of cellular adhesion, and matrix degradation enzymes, are also worthy of study. Although many previous studies have examined the relation of inflammation to myocardial infarction, emerging evidence suggests that other cardiovascular phenotypes such as ischemic stroke and early-stage atherosclerosis may also be related to inflammation. Further elucidating the role of inflammation in cardiovascular disease may lead to the identification of new targets for preventive or therapeutic interventions. In addition, markers of inflammation may be useful as a means to predict or monitor an individual's response to currently available cardiovascular therapies, such as aspirin or HMG coenzyme A reductase inhibitors, that may act via antiinflammatory mechanisms.
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PMID:Systemic inflammation as a cardiovascular disease risk factor and as a potential target for drug therapy. 1197 14

The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A reductase inhibitor, pravastatin, on exercise electrocardiography (ECG) test performance and cardiovascular mortality and morbidity were compared with those of conventional lipid-lowering drugs in hypercholesterolemic patients with no history of myocardial infarction or stroke. One thousand two hundred and seventeen patients were randomly assigned with mean serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels of 6.98 +/- 0.91mmol/L, 2.08 +/- 1.87mmol/L, 1.38 +/- 0.44mmol/L, and 5.07 +/- 1.14 mmol/L, respectively, and received either pravastatin at a dose of 10-20mg/day (group P) or one of the conventional lipid-lowering drugs such as fibrates, nicotinic acid, and probucol (group C). The numbers of patients available for analysis in groups P and C were 305 and 278 at year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and 103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in serum LDL cholesterol levels was significantly greater (p<0.01) in group P (-24.3%) than in group C (-16.0%). Serum HDL cholesterol levels increased in group P (+11.6%), but decreased in group C (-0.3%) (p<0.01). There were no significant differences in the rate of patients who exhibited ischemic changes to exercise ECG test (ischemic responders) between the 2 groups. Coronary heart diseases (CHD) occurred in 6 patients in group P and 13 in group C; pravastatin significantly reduced CHD risk (reduction rate 0.369; 95% confidence interval 0.140-0.970; p<0.05). No significant differences existed between the treatment groups in terms of the number of strokes (group P, 6; group C, 7) or deaths unrelated to CHD (group P, 3; group C, 2). Although pravastatin did not improve the proportion of ischemic responders on exercise testing, it reduced CHD risk and serum LDL cholesterol levels more significantly than conventional lipid-lowering drugs without adversely affecting the risk of stroke and non-CHD death in hypercholesterolemic patients.
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PMID:Effects of pravastatin on exercise electrocardiography test performance and cardiovascular mortality and morbidity in patients with hypercholesterolemia: Lipid Intervention Study in Kyoto. 1199 65

The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors or statins are potent inhibitors of cholesterol synthesis. Several large clinical trials have demonstrated that these agents reduce serum cholesterol levels and the incidence of cardiovascular diseases. However, overlap and meta-analyses of these clinical trials suggest that the beneficial effects of statins may extend beyond their effects on serum cholesterol levels. Because statins also inhibit the synthesis of isoprenoid intermediates in the cholesterol biosynthetic pathway, they may have pleiotropic effects on the vascular wall. In particular, the ability of statins to decrease the incidence of ischemic stroke highlights some of their non-cholesterol effects since serum cholesterol levels are poorly correlated with the risk for ischemic stroke.
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PMID:Statins and ischemic stroke. 1204 82

Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a seleno-organic compound with glutathione peroxidase-like activity is used in clinical trials against stroke. Human and bovine TrxR catalyzed the reduction of ebselen to ebselen selenol by NADPH with an apparent K(M)-value of 2.5 microM and a kcat of 588 min(-1). The addition of thioredoxin (Trx) stimulated the TrxR-catalyzed reduction of ebselen several-fold. This result was caused by a very fast oxidation of reduced Trx by ebselen with a rate constant in excess of 2 x 10(7) M(-1) s(-1). This rate is orders of magnitude faster than the reaction of dithiol Trx with insulin disulfides. Ebselen competed with disulfide substrates for reduction by Trx and, therefore, acted as an inhibitor of protein disulfide reduction by the Trx system. The inherent H2O2 reductase activity of mammalian TrxR dependent on its active-site selenocysteine residue was stimulated 10-fold by 2 microM ebselen and 25-fold in the additional presence of 5 microM Trx. Furthermore, the apparent K(M)-value of TrxR for H2O2 was lowered 25-fold to about 100 microM. Our results demonstrate that ebselen is a TrxR peroxidase which, in the presence of Trx, acted as a mimic of a peroxiredoxin. The activity with TrxR and oxidation of reduced Trx offer mechanistic explanations for the in vivo effects of ebselen as an antioxidant and anti-inflammatory agent. Our results demonstrate that the mechanism of action of ebselen may be predominantly via the Trx system rather than via glutathione.
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PMID:Ebselen: a substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant. 1207 Mar 43


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