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

Moderate hyperhomocysteinaemia is associated with atherosclerosis, thrombosis and also with stroke and dementia. Elevated homocysteine concentrations are related to deficiency of folate and also vitamin-B12, as these two vitamins are essential co-factors in the remethylation of homocysteine to methionine. A causal role of homocysteine in the pathogenesis of vascular disease has been discussed over years. Immune activation appears to be involved strongly in atherogenesis as well as in other diseases found to be associated with moderate hyperhomocysteinaemia. To study a possible influence of immune stimulation on homocysteine metabolism, in vitro experiments were performed using peripheral blood mononuclear cells upon stimulation with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen. In stimulated cells a dose-dependent increase of homocysteine concentrations was found. When cells were kept in medium supplemented with methionine, homocysteine concentrations increased further, while supplementation with folate had only a slight effect. We conclude that in supernatants of stimulated peripheral blood mononuclear cells homocysteine is accumulating. T cell activation could be involved in the development of moderate hyperhomocysteinaemia.
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PMID:Homocysteine accumulates in supernatants of stimulated human peripheral blood mononuclear cells. 1297 54

Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases.
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PMID:Glutathione metabolism and its implications for health. 1498 35

Plasma total homocysteine (tHcy) concentrations are associated with atherogenesis in adults and increased risk of stroke in infants and children. After a series of experiments to compare the methionine (Met) requirement and cysteine (Cys)-sparing capacity in piglets that were parenterally or enterally fed, we examined the effects of route of feeding and dietary Cys on plasma tHcy concentrations. Piglets (n = 60; 6-8 d old) were fed elemental diets, intragastrically (n = 28) or intravenously (n = 32), with 0.55 g. kg(-1). d(-1) dietary Cys (n = 28) or without dietary Cys (n = 32). Dietary Met ranged from deficient to excess. Increasing Met intake increased (P < 0.01) plasma tHcy in all treatment groups. Plasma tHcy concentrations were higher (P < 0.05) in the enterally fed piglets that did not receive dietary Cys than in all other groups, which did not differ from each other. Therefore, both route of feeding and dietary supply of Met and Cys significantly affected the concentrations of plasma tHcy. These dramatic and rapid alterations in plasma tHcy warrant further studies of sulfur amino acid metabolism in neonatal animals.
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PMID:The balance of dietary sulfur amino acids and the route of feeding affect plasma homocysteine concentrations in neonatal piglets. 1498 55

We conducted a case-control study to evaluate the relationship between ischemic stroke in young adults (<45 years of age) and plasma homocysteine (Hcy), plasma folate and vitamin B(12), after a methionine load. We studied 42 patients with a history of ischemic stroke and 29 controls with a negative clinical history of cardio- or cerebrovascular diseases, venous thrombosis and renal disease. A fasting blood sample was drawn from each participant; the second and third samples were collected, respectively, 120 and 240 min after the methionine load. Whilst there was no difference between controls and patients in basal total homocysteine (tHcy), we found a statistically significant difference in both the 120- and 240-min samples. We compared the basal and 240-min tHcy in patients and controls. We obtained a median value of 17.8 and 11.6 micromol/l in patients and controls, respectively. The difference between these two values was highly significant. The methionine loading test (MLT) reveals Hcy metabolism abnormalities that were not revealed by the basal sample. MLT may help identify and treat this new risk factor, which seems to be both atherogenic and prothrombotic, and is hypothesized to operate through various mechanisms.
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PMID:Young stroke and basal plasma and post-methionine load homocysteine and cysteine levels 1 year after the acute event: do plasma folates make the difference? 1506 29

In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues. The family members that are released into blood from periphery, especially gut, circulate the brain and they can cross the blood brain barrier. On the other hand, some of the members of this family that present in the brain, can cross from brain to blood and reach the peripheral targets. VIP, secretin, GLP(1), and PACAP 27 are transported into the brain by transmembrane diffusion, a non-saturable mechanism. However, uptake of PACAP 38 into the brain is saturable mechanism. While there is no report for the passage of GIP, GLP(2), and PHM, there is only one report that shows, glucagon and GHRH can cross the BBB. The passage of VIP/PACAP/secretin family members opens up new horizon for understanding of CNS effects of peripherally administrated peptides. There is much hope that those peptides may prove to be useful in the treatment of serious neurological diseases such as Alzheimer's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS related neuropathy, diabetic neuropathy, autism, stroke and nerve injury. Their benefits in various pathophysiologic conditions undoubtly motivate the development of a novel drug design for future therapeutics.
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PMID:Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. 1513 84

Molecular biology has recently contributed significantly to the recognition of selenium (Se)2 and Se-dependent enzymes as modulators of brain function. Increased oxidative stress has been proposed as a pathomechanism in neurodegenerative diseases including, among others, Parkinson's disease, stroke, and epilepsy. Glutathione peroxidases (GPx), thioredoxin reductases, and one methionine-sulfoxide-reductase are selenium-dependent enzymes involved in antioxidant defense and intracellular redox regulation and modulation. Selenium depletion in animals is associated with decreased activities of Se-dependent enzymes and leads to enhanced cell loss in models of neurodegenerative disease. Genetic inactivation of cellular GPx increases the sensitivity towards neurotoxins and brain ischemia. Conversely, increased GPx activity as a result of increased Se supply or overexpression ameliorates the outcome in the same models of disease. Genetic inactivation of selenoprotein P leads to a marked reduction of brain Se content, which has not been achieved by dietary Se depletion, and to a movement disorder and spontaneous seizures. Here we review the role of Se for the brain under physiological as well as pathophysiological conditions and highlight recent findings which open new vistas on an old essential trace element.
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PMID:Selenium and brain function: a poorly recognized liaison. 1521 Mar 2

Mitochondria serve as checkpoints and amplifiers on cell death pathways. In the central nervous system, mitochondrial involvement seems essential for normal expression of cell death phenotypes, and interference with these pathways thus seems a reasonable approach to neuroprotection. We have been involved in examining the potential involvement of the mitochondrial permeability transition (mPT) as one of several possible mechanisms by which mitochondria may be drawn into these death cascades. This possibility, though still controversial, is supported by evidence that factors that may stimulate mPT induction are associated with some forms of cell death (e.g., in stroke) and are modulated by diseases of the central nervous system (e.g., Huntington's). Evidence of neuroprotection seen with compounds such as N -Met-Val cyclosporine also support this possibility.
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PMID:The mitochondrial permeability transition as a target for neuroprotection. 1537 63

Homocysteine (Hcy) is a by-product of methionine metabolism. An imbalance of Hcy in the body may lead to hyperhomocysteinemia, a condition with elevated Hcy concentration in blood that may be one of the risk factors responsible for the development of several vascular diseases (thromboembolism, atherosclerosis, stroke, vascular diseases and dementia). Radix Salvia miltiorrhiza (Danshen), a well-known Chinese medicinal herb that can activate and improve blood microcirculation, is noticeable for its beneficial effect in treating cardiovascular diseases. The present study is to demonstrate the protective effect of Danshen extract against the homocysteine-induced adverse effect on human umbilical vein endothelial cell (HUVEC). Homocysteine (5 mM) not only decreased the cell viability but also caused the disruption of capillary-like structure formation in vitro. The protective effect of Danshen aqueous extract and its active compounds on endothelial cell function were demonstrated through an in vitro tube formation assay, which mimics the new blood vessel formation. To identify the active components in the aqueous extract of Danshen, the content was characterized by instrumental analysis using high performance liquid chromatography with diode array detector (DAD) and electrospray tandem mass spectrometry (ESI-MS/MS). Interestingly, Danshen extract and its pure compounds showed different effectiveness in protecting HUVEC against Hcy-induced injury according to the following descending order: Danshen aqueous extract, 3-(3,4-dihydroxy-phenyl)-2-hydroxy-propionic acid (Danshensu), protocatechuic acid, catechin and protocatechualdehyde. We believed that such findings might provide evidence in understanding the beneficial effects of Danshen on the cardiovascular system.
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PMID:Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. 1548 95

Homocystinuria is a congenital metabolic disorder, and has been known as life-threatening risk factor of vascular disease including ischemic stroke. We report a case of cerebral infarction due to homocystinuria. The patient was a 21-year-old woman exhibiting left hemiparesis and a previous history of ectopia lentis. Magnetic resonance imaging showed multiple fresh infarctions in the right frontal and temporal lobes, basal ganglia, corona radiata, and internal capsule. The right common carotid angiogram demonstrated complete occlusion at the origin of the right internal carotid artery. Further investigation clarified increased level of serum methionine and homocysteine and urinary homocystin due to cystathionine beta-synthase deficiency. Homocystinuria was diagnosed as the cause of cerebral infarction. The patient was treated by low methionine diet and administration of folic acid, cobalamin, and aspirin. It should be recognized that some patients with homocystinuria are missed in the neonatal screening for congenital metabolic disorders. Recent studies indicated that the homocysteinemia is one of risk factors of ischemic stroke in the general population as well as in the patients of homocystinuria. We recommend metabolic screening for homocystinuria, when treating a juvenile patient with ischemic stroke of unknown etiology.
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PMID:[A case of young adult presenting with cerebral infarction caused by homocystinuria]. 1555 67

Mitochondrial DNA 5178 C/A (mt5178 C/A), namely NADH dehydrogenase subunit 2 237 Leu/Met, polymorphism is as reported in literature associated with longevity and susceptibility to ischemic heart disease or cerebrovascular disorders in the Japanese population. Previous reports suggested that mt5178A genotype exerts antiatherogenic effects. The aim of this study was to investigate whether mt5178 C/A polymorphism is associated with hematological parameters, such as thrombogenic risk factors for myocardial infarction and stroke, in 321 healthy Japanese men. No significant differences were observed between mt5178 C/A genotypes, but in subjects with body mass index (BMI) of < or = 23, this polymorphism influenced the effects of habitual smoking on hematological parameters. Red blood cell (RBC) counts were significantly lower and mean corpuscular hemoglobin (MCH) levels were significantly higher in smokers with mt5178A than nonsmokers with mt5178A. Platelet counts were significantly higher in smokers with mt5178C than nonsmokers with mt5178C. Cigarette consumption was strongly associated with RBC counts, mean corpuscular volume levels, and MCH levels for men with mt5178A, and was associated with platelet counts for those with mt5178C. Moreover, BMI was significantly positively associated with RBC counts and platelet counts only in men with mt5178A, age was significantly negatively associated with RBC counts only in men with mt5178C. These data suggest that mt5178 C/A polymorphism may influence the effects of cigarette smoking on hematological parameters in healthy BMI < or = 23 Japanese men.
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PMID:Interaction between longevity-associated mitochondrial DNA 5178 C/A polymorphism and cigarette smoking on hematological parameters in Japanese men. 1568 Apr 95


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