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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneously hypertensive rat (stroke-prone) (SHRSP) has an interestingly low serum cholesterol level due to a reduced biosynthesis of cholesterol in the liver (Iritani, N., Fukuda, E., Nara, Y., and Yamori, Y. (1977) Atherosclerosis 28, 217-222). In this study, we examined the mechanism underlying the reduction of hepatic cholesterol biosynthesis in the rat. Our initial findings in SHRSP, as compared with normotensive Wistar Kyoto rat (WKY), showed that 1) the incorporation of [14C]acetate into cholesterol in the liver slices was markedly less, 2) 3-hydroxyl-3-methylglutaryl (HMG) CoA reductase activity was not reduced, and 3) the incorporation of [3H]mevalonic acid into both cholesterol and squalene was significantly less. The above initial findings suggested that the reduction in the hepatic cholesterol biosynthesis took place in one or more enzymatic processes starting with mevalonic acid and continuing to squalene. When the incorporation of [3H]mevalonic acid into phosphomevalonate derivatives was studied using an ion exchange column, only the radioactivity incorporated into isopentenyl-pyrophosphate (isopentenyl-PP) was less in SHRSP. Furthermore, the specific activity of diphosphomevalonate (mevalonate-PP) decarboxylase in the liver-soluble fractions was reduced 50% in SHRSP as compared with WKY. Kinetic studies using liver crude extracts indicated a lower Vmax value in SHRSP (SHRSP, 0.47; WKY, 2.05 nmol/min/mg), and an unchanged Km value (SHRSP, 18.2; WKY, 19.6 microM). The activity of mevalonate-PP decarboxylase was also found to be reduced in other tissues, including the brain, testis, small intestine, and cultured vascular smooth muscle cells. From the above observations, we concluded that the lower activity of mevalonate-PP decarboxylase was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP.
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PMID:Liver mevalonate 5-pyrophosphate decarboxylase is responsible for reduced serum cholesterol in stroke-prone spontaneously hypertensive rat. 155 16

A 24-year-old male had a deficiency of the complex I (NADH coenzyme-Q-reductase) of the mitochondrial respiratory chain, which clinically presented as a mitochondrial encephalomyopathy, with lactic acidosis and stroke-like episodes (MELAS syndrome). The encephalopathic episodes were preceded by migraine and were characterized by focal deficit signs, motor partial seizures and hypodense areas in the CT scan. An echocardiographic diagnosis of hypertrophic cardiomyopathy without intracavitary thrombi was made. It is suggested that hypertrophic cardiomyopathy is caused by the mitochondrial abnormalities that have been reported in the myocardium, and that migraine and cerebral infarctions are associated with abnormalities in the mitochondria from the endothelium and smooth muscle fibres of the cerebral small arteries and arterioles.
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PMID:[Complex I (NADH coenzyme-Q-reductase) deficiency, MELAS syndrome and hypertrophic cardiomyopathy]. 190 55

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10(CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase-coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than in blood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.
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PMID:Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10. 725 68

NADPH-dependent methemoglobin reductase, first detected in erythrocytes sixty years ago, has subsequently been purified and characterized as a methylene blue reductase and a flavin reductase. The reductase plays no role in methemoglobin reduction under normal conditions, but its activity serves as the basis for the treatment of methemoglobinemia with methylene blue or flavin. On-going studies demonstrate that this cytosolic protein is also present in liver and that its primary structure distinguishes it from other known proteins. The bovine erythrocyte reductase tightly binds hemes, porphyrins, and fatty acids with resulting loss of activity. Pyrroloquinoline quinone serves as a high-affinity substrate of the reductase, suggesting that this naturally-occurring compound may be a physiological substrate. The ability of the reductase to catalyze the intracellular reduction of administered riboflavin to dihydroriboflavin suggested that this system might be exploited to protect tissues from oxidative damage. This hypothesis was supported by our finding that dihydroriboflavin reacts rapidly with Fe(IV)O and Fe(V)O oxidation states of hemeproteins, states that have been implicated in tissue damage associated with ischemia and reperfusion. Preliminary studies demonstrate that, as predicted, administration of low concentrations of riboflavin protects isolated rabbit heart from reoxygenation injury, rat lung from injury resulting from systemic activation of complement, and rat brain from damage caused by four hours of ischemia. Data from these animal studies suggest that flavin therapy holds promise in protecting tissue from the oxidative injuries of myocardial infarction, acute lung injury, stroke, and a number of other clinical conditions.
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PMID:Evidence that NADPH-dependent methemoglobin reductase and administered riboflavin protect tissues from oxidative injury. 841 88

Advances in stroke therapy have followed diverse paths over the past 2 years. Recent clinical trials have investigated the use of thrombolytic agents, anticoagulants, antiplatelet drugs and neuroprotective agents in acute stroke patients. The positive results of the National Institutes of Neurologic Disease and Stroke tissue plasminogen activator trial have increased interest in the field of acute stroke therapy and initiated significant changes in the management of stroke patients in the medical system. A new antiplatelet drug and a number of trials involving HMG Co-A reductase inhibitors are important advances in the secondary prevention of stroke.
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PMID:Recent advances in stroke therapy. 948 18

Although associations of cholesterol and coronary heart disease (CHD) are well accepted, the association between cholesterol and stroke has been a subject of some confusion. Epidemiologic evidence suggests no association between plasma concentrations of cholesterol and stroke, and earlier clinical trials were also negative. Two early meta-analyses of clinical trials designed to evaluate the effects of cholesterol lowering on CHD concluded that cholesterol lowering had no effect. More recently newer, more potent and better tolerated agents (HMG-CoA reductase inhibitors, reductase inhibitors) have become available and have been tested for their efficacy in reducing cholesterol and CHD in both primary prevention and secondary prevention trials. Meta-analyses of these trials, in contrast to the earlier trials, reveal a powerful statistically significant effect to reduce stroke as well as CHD in secondary prevention (30%); the direction of the effect is the same in trials of primary prevention or trials that randomized patients with and without CHD (mixed primary and secondary prevention trials) where the risk reductions for stroke, although not reaching statistical significance are 11 and 30%, respectively. An important difference in the newer analysis is the availability of several trials of secondary prevention in which low density lipoprotein cholesterol was lowered 25-30% and in which CHD event reduction was similarly reduced by 30%. Mechanisms for stroke reduction likely involve retardation of plaque progression in the intracranial and extracranial carotid arteries, plaque stabilization, and, in addition, stroke may be reduced partly as a consequence of CHD reduction.
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PMID:HMG-CoA reductase inhibitor therapy and stroke risk reduction: an analysis of clinical trials data. 967 67

Hyperlipidemia is recognized as one of the major risk factors for the development of coronary artery disease and progression of atherosclerotic lesions. Dietary therapy together with hypolipidemic drugs are central to the management of hyperlipidemia, which aims to prevent atherosclerotic plaque progression, induce regression, and so decrease the risk of acute coronary events in patients with pre-existing coronary or peripheral vascular disease. In patients at high risk of coronary artery disease but without evidence of atherosclerosis, treatment is designed to prevent the premature development of coronary artery disease, whereas in those with hypertriglyceridemia, treatment aims to prevent the development of hepatomegaly, splenomegaly, and pancreatitis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent lipid-lowering agents currently available, and their use in the treatment of hyperlipidemia provides the focus for this review. Particular emphasis is given to cerivastatin, a new HMG-CoA reductase inhibitor that combines potent cholesterol-lowering properties with significant triglyceride-reducing effects. Recently completed primary and secondary intervention trials have shown that the significant reductions in low-density lipoprotein (LDL) cholesterol achieved with statins result in significant reductions in morbidity and mortality associated with coronary artery disease as well as reductions in the incidence of stroke and total mortality. Such benefits occur early in the course of statin therapy and have led to suggestions that these drugs may possess antiatherogenic effects over and above their capacity to lower atherogenic lipids and lipoproteins. Experimental studies have also shown statin-induced improvements in endothelial function, decreased platelet thrombus formation, improvements in fibrinolytic activity, and reductions in the frequency of transient myocardial ischemia.
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PMID:Current and future treatment of hyperlipidemia: the role of statins. 973 40

High levels of homocysteine are associated with atherosclerosis. A thermolabile form of the enzyme methylene tetrahydrofolate reductase (MTHFR) has been proposed as a major cause of a genetic predisposition to hyperhomocysteinaemia and a point mutation at nucleotide 677 of the MTHFR gene causing a thermolabile MTHFR has been described. We looked for this mutation in 271 patients with CT proven cerebrovascular accidents and 173 control subjects. No significant difference in the frequency of the mutant genotype was found between patients with strokes and the control group. Separate analysis of those under 65 and subdividing stroke patients by anatomical location also revealed no significant difference. We conclude, therefore, that in this population the mutation evaluated is not a major contributor to the aetiology of cerebrovascular disease.
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PMID:Methylene tetrahydrofolate reductase C677T genotype and stroke. 995 81

The balance of evidence from observational studies suggests that elevated levels of homocysteine are associated with increased risk of carotid artery disease and stroke. There is, however, a paucity of prospective studies. There are also concerns regarding confounding caused by factors associated with hyperhomocysteinaemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of methylene-tetrahydrofolate reductase, a common genetic polymorphism which results in hyperhomocysteinaemia, has not been consistently linked with stroke or other vascular diseases. Additional prospective studies are required, with sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and hypertension. Ultimately, the case for a causal role for elevated levels of homocysteine in vascular disease, including stroke, will depend on data from randomised controlled trials of homocysteine-lowering interventions. Given the high prevalence of hyperhomocysteinaemia in apparently well-nourished populations and the tendency for homocysteine concentrations to increase with age, modest effects of homocysteine on stroke risk will have profound implications for public health.
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PMID:Homocysteine and risk of stroke. 1050 Dec 75

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors--"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti-ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.
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PMID:The evolving role of statins in the management of atherosclerosis. 1063 52


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