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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired homocysteine metabolism might be a risk factor for vascular disease. Peroral methionine loading and post-load determination of methionine and homocysteine in plasma has frequently been used for identifying subjects with genetically impaired homocysteine metabolism. However, a methionine-rich diet induces a more efficient homocysteine catabolism in the rat, which suggests that humans on diets with differing methionine content might respond differently to the methionine loading test. To study this we performed methionine loading in six healthy subjects before and after 2 wk of excessive daily methionine intake (300% of normal). On each occasion plasma homocysteine and methionine were measured at several intervals post-load. However, neither the methionine clearance nor the post-load homocysteine concentrations were affected by excess methionine. We conclude that variations in the daily methionine intake will not influence the methionine loading test.
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PMID:The effect of excess daily methionine intake on plasma homocysteine after a methionine loading test in humans. 226 99

Homocystinuria is an inborn error of methionine metabolism, of which cause is mainly deficiency of cystathionine synthetase. The major clinical manifestations of homocystinuria are mental retardation, seizures, ectopia lentis, skeletal deformities and occlusive vascular disease. A case of homocystinuria accompanied with deep cerebral venous thrombosis was reported. A 29-year-old woman was admitted to our hospital with unconsciousness and tetraparesis on December 7, 1984. She was diagnosed as homocystinuria due to cystathionine synthetase deficiency at 13-year-old. Amino acid analysis of serum revealed homocystinaemia (1.37 mg/dl, normal 0), hypermethioninaemia (1.27 mg/dl, normal 0.2-0.48) and low cystathionine content. CT scan revealed intraventricular hemorrhage and diffuse low density in basal ganglia and white matter. Cerebral angiograms showed that deep cerebral veins and superior sagittal sinus can not be recognized clearly in any phase, and Sylvian veins are opacified markedly. It is suggested that intraventricular hemorrhage, and low density area in basal ganglia and white matter is due to hemorrhagic infarction by venous thrombosis of internal cerebral vein. The major clinical manifestations of homocystinuria result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Homocystinuria accompanied with cerebral deep venous thrombosis--a case report]. 236 35

Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.
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PMID:Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. 240 53

Thrombogenesis and accelerated atherogenesis occur in the homocystinurias, both those due to recessively inherited cystathionine beta-synthase deficiency and to disorders of remethylation of homocysteine to methionine. The evidence strongly implicates high levels of plasma homocysteine as the mediator. Homocysteine damages cultured human venous and arterial endothelial cells and enhances detachment from their substrate, changes not found with comparable concentrations of other amino acids tested. Homocysteine is oxidized in vitro to homocystine in an oxygen-dependent reaction producing hydrogen peroxide. Since the effects of homocysteine in cell cultures can be prevented by catalase, hydrogen-peroxide-induced injury may be the mechanism responsible. Five different laboratories have documented an association between mild homocysteinaemia and premature vascular disease. The majority of affected patients are heterozygotes for cystathionine beta-synthase deficiency whose endothelial cells may have an enhanced susceptibility to injury by homocysteine. Mild homocysteinaemia also occurs in chronic renal failure in which vascular disease is prominent. Mechanisms linking mild homocysteinaemia and possible vascular effects are not yet understood, but could involve prostaglandins and oxidized low-density lipoprotein, and possibly also free radicals.
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PMID:Mechanisms of thrombogenesis and accelerated atherogenesis in homocysteinaemia. 268 Aug 9

In three different studies we tested the hypothesis that early-onset vascular disease is associated with impaired homocysteine metabolism which could contribute to the development of arteriosclerosis and thrombosis. In patients with occlusive vascular disease before the age of 60, a post-methionine load increase of plasma homocysteine exceeding the highest value for comparable healthy control subjects was found in 1 of 21 with myocardial infarction (5%), 14 of 37 with aorto-iliac disease (38%), and 17 of 53 with cerebrovascular disease (32%). This might indicate heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency. Concentrations of serum vitamin B12 and red cell folate had an important modulating effect on plasma homocysteine concentrations in the fasting state.
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PMID:Plasma homocysteine and methionine tolerance in early-onset vascular disease. 268 Aug 11

Sulfur amino acids have been implicated in the pathogenesis of thromboembolic vascular disease, and observations of patients with several inborn errors of metabolism have led to the 'homocysteine theory of arteriosclerosis'. Homocysteine is an intermediate in the transsulfuration pathway and it enters into several other reactions, some of which involve transfer of methyl groups. An abnormally high concentration of homocysteine in the blood causes homocystinuria. Deficiency of cystathionine beta-synthase is the most frequent cause of homocystinuria. Patients with this disorder are at risk for early vascular occlusions. Treatment with vitamin B6 of patients who are biochemically responsive to this vitamin reduces the risk of thromboembolism. Clinical or pathologic evidence of early vascular disease has also been provided in patients with homocysteinemia due to deficient (re)methylation of homocysteine to methionine. This may be caused by a deficiency of 5,10-methylenetetrahydrofolate reductase or by a deficient synthesis of cobalamins.
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PMID:Inborn errors of metabolism causing homocysteinemia and related vascular involvement. 268 Aug 12

Reduction of circulating homocysteine levels by folic acid suggests an additional approach to the prophylaxis of certain forms of vascular disease related to atherogenic amino acids.
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PMID:Homocysteine, folic acid, and the prevention of vascular disease. 268 69

Severe homocystinemia is frequently associated with vascular disease while the pathological consequences of moderate or slightly elevated plasma homocysteine are unknown. Cobalamin and folate deficiencies may result in an elevation of plasma homocysteine. A sensitive and reproducible assay for total plasma homocysteine has been developed. The essential steps in the assay include (i) conversion of homocysteine disulfides to free homocysteine with borohydride reduction; (ii) conjugation of homocysteine with monobromobimane; (iii) separation of homocysteine-bimane from other plasma thiol-bimane adducts by reverse-phase high-performance liquid chromatography; and (iv) detection and quantitation of homocysteine-bimane by fluorometry. The method has a sensitivity of 4.4 pmol of homocysteine and is highly reproducible (intra- and interassay coefficients of variation = 4.97 and 4.53%, respectively). The mean concentration of total plasma homocysteine in nonfasting adult males (n = 12) and females (n = 12) was 15.8 (range, 7.0-23.7) and 16.5 nmol/ml (range, 8.6-20.7), respectively. Markedly elevated levels of homocysteine were found in patients with cobalamin and folate deficiency. Total plasma homocysteine represents approximately 4% of borohydride-generated thiol reactivity in the plasma of normal individuals.
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PMID:Determination of plasma homocysteine by high-performance liquid chromatography with fluorescence detection. 272 75

Catabolism of methionine is supposed to proceed via two known pathways: transsulphuration and transamination. In 10 premenopausal women and 13 young men we measured methionine, the transsulphuration metabolite homocysteine, and the transamination metabolites 4-methylthio-2-oxo-butryate and methanethiol mixed disulphides in the fasting state as well as after oral administration of 0.1 g L-methionine kg-1 body weight. Both in the fasting state and after methionine loading the concentrations of homocysteine in serum were significantly lower in premenopausal women than in young men. Since there is evidence that even a moderate homocysteinaemia may be a risk factor in the development of vascular disease, the low homocysteine levels could be an additional factor contributing to the lower incidence of vascular disease in premenopausal women. After oral methionine these women showed significantly higher concentrations both in serum and urine of the transamination metabolites than the group of men. This higher methionine transamination in premenopausal women may contribute to keeping the homocysteine levels low and may therefore have an impact on the protection of these women against vascular disease.
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PMID:Differences between premenopausal women and young men in the transamination pathway of methionine catabolism, and the protection against vascular disease. 314 89

Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12-deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease.
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PMID:Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency. 334 5


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