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

Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+]i in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+]i. HC, methionine and cysteine did not produce any changes in [Ca2+]i. Lowering [Mg2+]o to 0.3 mM resulted in elevation of [Ca2+]i and loss of [Mg2+]i. Depletion of [Mg2+]i, induced by HC, was potentiated by low Mg2+. Preincubation of these cells with vitamin B6, vitamin B12, folic acid, alone, did not alter [Ca2+]i or [Mg2+]i. Likewise, concomitant addition of vitamin B6, vitamin B12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+]i induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+]i. Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+]i induced by low [Mg2+]i, but it did suppress the rise in [Ca2+]i. Interestingly, in the presence of low [Mg2+]o, the vitamin combination did not retard depletion of [Mg2+]i. The present findings are compatible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+]i depletion and occlusive cerebral vascular diseases induced by homocysteinemia.
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PMID:Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]i, atherogenesis and stroke. 1055 43

Homocysteine is a sulphur-containing amino acid formed during metabolism by one of two pathways by remethylation and transsulfuration. Altered homocysteine metabolism may be implicated as a factor in atherosclerosis, cerebrovascular disease or peripheral vascular disease. It is postulated that homocysteine may damage endothelial cells or acts as a direct causal factor in the thromboembolic process. Several studies have reported that there are a number of factors that may influence levels of homocysteine in humans. Serum homocysteine levels may be associated with low levels of folate, vitamin B6 and vitamin B12. These studies showed that serum homocysteine levels were higher in men and older adults, and some showed that there was a direct relationship between homocysteine and cigarette smoking, diabetes, obesity, and hypertension. Subjects who consume larger amounts of coffee were also noted to have higher serum homocysteine levels. Several cross-sectional, case-control, and cohort studies have linked homocysteinaemia with cardiovascular disease morbidity and mortality. In the Framingham Heart Study, the cohort study in Tromso, Norway, and the Atherosclerosis Risk in Communities (ARIC) Study, homocysteine levels were found to be higher in adults with asymptomatic or symptomatic coronary artery disease. In the British Regional Heart Study, homocysteine levels were found to be significantly higher in patients with stroke. Thus, there are suggestions that vitamin therapy and alteration of lifestyle habits such as cigarette smoking may lower homocysteine levels. There may be less coronary heart disease morbidity and mortality with lower homocysteine levels.
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PMID:Homocysteine and atherosclerotic disease: the epidemiologic evidence. 1056 72

The positive correlation existing between hyperhomocyst(e)inemia [HH(e)] and vascular disease has firmly been established through data derived from numerous epidemiological and experimental observations. Clinical data corroborate that homocysteine (Hcy) is an independent risk factor for coronary, cerebral and peripheral arterial occlusive disease or peripheral venous thrombosis. Hcy is a sulfhydryl-containing amino acid that is formed by the demethylation of methionine. It is normally catalyzed to cystathionine by cystathionine beta-synthase a pyridoxal phosphate-dependent enzyme. Hcy is also remethylated to methionine by 5-methyltetrahydrofolate-Hcy methyltransferase (methionine synthase), a vitamin B12 dependent enzyme and by betaine-Hcy methyltransferase. Nutritional status such as vitamin B12, or vitamin B6, or folate deficiencies and genetic defects such as cystathionine beta-synthase or methylene-tetrahydrofolate reductase may contribute to increasing plasma homocysteine levels. The pathogenesis of Hcy-induced vascular damage may be multifactorial, including direct Hcy damage to the endothelium, stimulation of proliferation of smooth muscle cells, enhanced low-density lipoprotein peroxidation, increase of platelet aggregation, and effects on the coagulation system. Besides adverse effects on the endothelium and vessel wall, Hcy exert a toxic action on neuronal cells trough the stimulation of N-methyl-D-aspartate (NMDA) receptors. Under these conditions, neuronal damage derives from excessive calcium influx and reactive oxygen generation. This mechanism may contribute to the cognitive changes and markedly increased risk of cerebrovascular disease in children and young adults with homocystunuria. Moreover, during stroke, in hiperhomocysteinemic patients, disruption of the blood-brain barrier results in exposure of the brain to near plasma levels of Hcy. The brain is exposed to 15-50 microM H(e). Thus, the neurotoxicity of Hcy acting through the overstimulation of NMDA receptors could contribute to neuronal damage in homocystinuria and HH(e). Since HH(e) is associated with certain neurodegeneratives diseases, in the present review, the molecular mechanisms involved in neurotoxicity due to Hcy are discussed.
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PMID:[Hyperhomocysteinemia: atherothrombosis and neurotoxicity]. 1079 37

The aim of this study was to investigate a possible association among the thermolabile polymorphism, nucleotide 677 cytosine to thymidine point mutation (677 C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene, hyperhomocysteinemia, serum folate, vitamins B12 and B6, and stroke in children. Allele and genotype frequencies for the 677 C-->T polymorphism in 21 children with stroke and 28 healthy children of the same age were studied. No differences in allelic frequency were detected between the two populations. However, the prevalence of homozygous 677 C-->T was doubled in the stroke population (28.6%) compared to the healthy group (14.3%). Total plasma homocysteine (tHcy) levels were significantly increased in children aged 2 months to 15 years with stroke compared to reference values. No association was observed between the homozygous genotype (T/T) and hyperhomocysteinemia, nor between the T/T genotype and low folate levels (below the 95th percentile) in this group of patients. Vitamin concentrations in patients were not significantly different from reference values. Significant negative correlations were found between tHcy and folate and between tHcy and cobalamin, but not between tHcy and B6 concentrations. In summary, a higher prevalence of hyperhomocysteinemia and the 677 C-->T polymorphism were observed in children with stroke, but were not always associated. The systematic study of both abnormalities in children with stroke is recommended, so that hyperhomocysteinemia of any genetic origin can be corrected with vitamin supplementation. Moreover, the 677 C-->T genotype is a strong factor for predisposition to hyperhomocysteinemia and recurrent risk of stroke that might also be prevented with folate supplementation.
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PMID:Children with stroke: polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status. 1083 Jan 95

Observational studies support the role of modifying lifestyle-related risk factors such as diet, physical activity and alcohol use in stroke prevention. For example, increased Na intake is associated with hypertension, and reduction in salt consumption may significantly lower blood pressure and may reduce stroke mortality. Moderately elevated homocysteine levels may be associated with stroke and are associated with deficiency of dietary intake of folate, vitamin B6 and vitamin B12. Consumption of a diet rich in fruits, vegetables, folate, K, Ca, Mg, dietary fibre, fish and milk may protect against stroke. Regular physical activity may also protect against stroke through its role in controlling various risk factors such as hypertension, diabetes mellitus and obesity. The role of fat intake as a risk factor for stroke remains uncertain, whereas the association between stroke and cholesterol has more convincingly been demonstrated by the recent intervention trials using statins. There is also evidence that a low serum albumin may be causally linked to stroke risk and outcome and that a significant number of stroke patients are undernourished on admission and their nutritional status deteriorates further whilst in hospital. Undernutrition is associated with increasing morbidity and mortality and nutritional supplements may have some beneficial effect on some outcome measures.
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PMID:Nutritional factors in stroke. 1096 Nov 55

Elevated plasma levels of homocyst(e)ine [H(e)] are surprisingly common and strongly associated with endothelial dysfunction and a marked increase in vascular risk. Treatment with a combination of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12) reduces plasma H(e) levels in most cases, restores endothelial function, and regresses carotid plaque, but there is no evidence that such treatment will reduce clinical events. The Vitamin Intervention for Stroke Prevention (VISP) study is a double-masked, randomized, multicenter clinical trial designed to determine if, in addition to best medical/surgical management, high-dose folic acid, vitamin B6, and vitamin B12 supplements will reduce recurrent stroke compared to lower doses of these vitamins. Patients at least 35 years old with a nondisabling ischemic stroke within 120 days, and screening plasma H(e) > the 25th percentile of benchmark population data are eligible. Secondary endpoints are myocardial infarction or fatal coronary heart disease. This paper describes the design and rationale of the study.
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PMID:Vitamin Intervention for Stroke Prevention (VISP) trial: rationale and design. 1117 41

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the C677T and the A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Blood tHcy was significantly higher in men from the CHD high risk town of Dewsbury (12.7 micromol/l) than in the low CHD risk town of Maidstone (11.5 micromol/l) P<0.001, but not in women (10.7 vs. 10.5 micromol/l), with women in both towns, thus, showing significantly lower tHcy than men. There was no difference between towns in folate or vitamin B12 levels but the conventional inverse relationship with tHcy was seen. Smoking men and women from both towns had significantly higher tHcy and lower folate levels than non-smoking individuals (P<0.001). The frequency of the 677T allele in Dewsbury was 0.35 (95% CI; 0.32-0.39) compared with 0.29 (95% CI; 0.26-0.32) in Maidstone (P<0.01). Similar frequency difference of borderline statistical significance was seen both for men (P=0.054) and women (P=0.048) in both the towns, suggesting a true regional frequency difference. The effect of the 677T on tHcy was highly significant in the group as a whole with the most profound effect seen in men (12.0 micromol/l for CC vs. 14.1 micromol/l for TT, P<0.001). By contrast, there was no significant effect of the A1298C polymorphism on tHcy, folate or vitamin B12 levels, with no evidence for an interaction with the C677T genotype. The regional differences in tHcy levels were still present after the adjustment for folate and vitamin B12 levels, smoking and the effect of the C677T polymorphism. This suggests that there may be other unidentified factors, either environmental or genetic, affecting tHcy levels, and thus potentially having an impact on the risk of developing hyperhomocysteinaemia and CHD. These observations may have a bearing on regional differences in tHcy levels and the variation in CHD risk between regions in the UK.
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PMID:The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. 1125 67

The aim of this study is to evaluate whether any relationship between stroke and vitamin B12, folic acid concentration. We examined 50 patients with stroke (male: 26 and female: 24) aged between (mean +/- SD, year) 59 +/- 14 and 16 control subjects (male: 6 and female: 10) aged between (mean +/- SD, year) 53 +/- 11. Patients were classified into two groups as infarct and hemorrhagic by using Computerised Brain Tomography and Cranial Nuclear Magnetic Resonance Imaging techniques. The percentage of patients with infract was 47.5% in female and 52.5% in male while it was 40% in female and 60% in male with hemorrhagic. The vitamin B12 levels of patients with infarct, hemorrhagic and control group were found as mean +/- SEM, 355 +/- 47 pg/ml, 313 +/- 58 pg/ml, 1569 +/- 258 pg/ml and folic acid levels 13.4 +/- 2.6 ng/ml, 7.7 +/- 1.0 ng/ml, 14.8 +/- 4.0 ng/ml, respectively. The significant difference was found between subgroups of patients with stroke and control group in both folic acid and B12 vitamin levels (p < 0.001 and p < 0.0001, respectively). But, there was no significant difference between vitamin B12 and folic acid levels of patients with hemorrhagic and infarct. In order to well understand the effects of these vitamin in patients with stroke, more detailed follow up studies with long period are needed.
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PMID:Determination of serum B12 vitamin and folic acid levels in patient with stroke. 1136 91

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

Recent studies have shown that hyperhomocysteinaemia is a common, independent and easily modifiable risk factor for atherosclerotic and thromboembolic diseases such as cerebrovascular disease, coronary artery disease and venous thrombosis. The vascular risk rises continuously across the spectrum of elevated plasma homocysteine concentrations. It is at least as important as cholesterol, lipoprotein abnormalities and hypertension and should be part of risk assessment, especially those at high risk. Moderately elevated plasma homocysteine concentration is readily correctable by folic acid, betaine, or vitamin B12 supplementation. It seems logical to assume that a reduction in homocysteine concentration will reduce the risk of ischaemic stroke, but there are as yet no published data to prove this. This review will discuss the aetiology and possible treatment of hyperhomocysteinaemia causing ischaemic stroke.
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PMID:Aetiology and treatment of hyperhomocysteinaemia causing ischaemic stroke. 1140 12


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