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

The effects of python neuropeptide gamma (NPgamma) on hemodynamic parameters have been investigated in the anesthetized ball python (Python regius). Bolus intra-arterial injections of synthetic python NPgamma (1-300 pmol kg-1) produced a dose-dependent decrease in systemic arterial blood pressure (Psys) concomitant with increases in systemic vascular conductance (Gsys), total cardiac output and stroke volume, but only minor effects on heart rate. The peptide had no significant effect on pulmonary arterial blood pressure (Ppul) and caused only a small increase in pulmonary conductance (Gpul) at the highest dose. In the systemic circulation, the potency of the NK1 receptor-selective agonist [Sar9,Met(0(2))11] substance P was >100-fold greater than the NK2 receptor-selective agonist [betaAla8] neurokinin A-(4-10)-peptide suggesting that the python cardiovascular system is associated with a receptor that resembles the mammalian NK1 receptor more closely than the NK2 receptor. Administration of the inhibitor of nitric oxide synthesis, L-nitro-arginine-methylester (L-NAME; 150 mg kg-1), resulted in a significant (P<0.05) increase in Psys as well as a decrease in Gsys, but no effect on Ppul and Gpul. Conversely, the nitric oxide donor, sodium nitroprusside (SNP; 60 microg kg-1) produced a significant (P<0.05) decrease in Psys along with an increase in Gsys and pulmonary blood flow. However, neither L-NAME nor indomethacin (10 mg kg-1) reduced the cardiovascular responses to NPgamma. Thus, nitric oxide is involved in regulation of basal vascular tone in the python, but neither nitric oxide nor prostaglandins mediate the vasodilatory action of NPgamma.
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PMID:Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius. 1572 83

1. Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke and renal failure. The incidence of hypertension is 25-30% in the adult Caucasian population and complications due to hypertension are even greater in African Americans. 2. The renin-angiotensin system plays an important role in the regulation of blood pressure and previous studies have suggested that angiotensinogen (AGT) gene locus is linked with human essential hypertension. Earlier studies suggested that a single nucleotide polymorphism (SNP) that converts methionine to threonine at amino acid 235 is associated with hypertension in the Caucasian population. However, this SNP is not associated with hypertension in African American and Chinese populations. 3. We have found an A/G polymorphism at -217 of the human AGT gene promoter and have shown that the frequency of allele A at -217 is significantly increased in the genomic DNA of African American hypertensive patients. 4. We have also shown that: (i) reporter constructs containing the AGT gene promoter with nucleoside A at -217 have increased promoter activity on transient transfection; and (ii) the CCAAT box enhancer binding protein (C/EBP) family of transcription factors and glucocorticoid receptor (GR) bind preferentially to this region of the promoter when nucleoside A is present at -217. In addition, variant -217A is always present with variants -532T, -793A and -1074T in the human AGT gene promoter. 5. These data suggest that the AGT haplotype containing -217A, -532T, -793A and -1074T may be involved in increased transcription of this gene and may play a role in human hypertension.
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PMID:A haplotype of the angiotensinogen gene is associated with hypertension in african americans. 1585 65

Moderate hyperhomocysteinaemia is established as an independent risk factor for atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly caused by the deficiency of B-vitamins folate and vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic diseases, in which also elevated immune activation markers such as neopterin or sTNFR-II are found. In order to simulate immune activation in vitro, human peripheral blood mononuclear cells (PBMC) were stimulated with mitogens. Stimulation significantly increased homocysteine production in comparison with unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine formation was due to cell proliferation, proliferating T lymphocytes, and also the myelomonocytic cell line U-937 produced homocysteine. Treatment with the anti-inflammatory drug aspirin dose-dependently inhibited homocysteine production and also neopterin formation in human PBMC. Treatment with salicylic acid showed similar effects as aspirin; FACS analysis showed that both compounds inhibited cell proliferation by arresting cells in the G0/G1-phase. In U-937, both compounds also slightly induced apoptosis at 5 mm. Proliferation-induced homocysteine formation and in parallel also monocyte activation can be suppressed effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo aspirin may downregulate not only inflammation but also formation of homocysteine.
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PMID:Aspirin downregulates homocysteine formation in stimulated human peripheral blood mononuclear cells. 1610 22

Metabolic conversion of homocysteine (Hcy) to a chemically reactive metabolite, Hcy-thiolactone, catalyzed by methionyl-tRNA synthetase is the first step in a pathway that is suggested to contribute to Hcy toxicity in humans. The accumulation of Hcy-thiolactone is detrimental because of its intrinsic ability to modify proteins by forming N-Hcy-protein adducts, in which a carboxyl group of Hcy is N-linked to the epsilon-amino group of a protein lysine residue. N-linked Hcy occurs in each protein examined and constitutes a significant pool of Hcy in the blood. N-Hcy proteins are likely to be recognized as neo-self antigens and induce an autoimmune response. Indeed, we found that autoantibodies specific for an Nepsilon-Hcy-Lys epitope on N-Hcy-proteins occur in humans. Serum levels of anti-N-Hcy-protein autoantibodies are directly correlated with plasma tHcy, but not with plasma cysteine or methionine levels. In a group of male patients with stroke, levels of anti-N-Hcy-protein autoantibodies and tHcy were significantly higher than in a group of healthy subjects. In a group of male patients with angiographically documented coronary artery disease, seropositivity for anti-N-Hcy-protein autoantibodies occurred five-fold more frequently than in controls and was an independent predictor of coronary artery disease. These findings show that the formation of N-Hcy-proteins has important physiological consequences and support a hypothesis that N-Hcy-protein is a neo-self antigen that contributes to immune activation, an important modulator of atherogenesis.
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PMID:Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease. 1619 90

Homocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.
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PMID:Homocysteine and thrombosis: from basic science to clinical evidence. 1636 30

Stroke-prone spontaneously hypertensive (SHRSP) rats are considered a suitable model for studying the effects of dietary and other environmental factors on human essential hypertension and haemorrhagic stroke. To investigate the suitability of a control diet for this strain of rats, we studied the effects of supplementing casein and soya protein isolate (SPI) with two sulphur amino acids (methionine and cystine) on the growth and lifespan of SHRSP rats. The source of dietary protein and the type of supplemental sulphur amino acid had significant (P < 0.05) effects on food intake and weight gain measured after 31 d of the feeding study, while only the type of supplemental sulphur amino acid had significant effects on mean survival times and the survival rates. On average, the casein groups had higher food intake and weight gain compared with the SPI groups. The methionine-supplemented groups had lower food intake but higher weight gain than the cystine-supplemented groups. Similarly, the methionine-supplemented groups had higher mean survival times and survival rates compared with the cystine-supplemented groups. The data would suggest that a control diet based on cystine-supplemented casein (as recommended for normal healthy rats by the American Institute of Nutrition), may not meet the sulphur amino acid requirements for SHRSP rats, and that the methionine-supplemented casein would be an appropriate control diet for this animal model.
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PMID:Effects of supplemental cystine or methionine on growth and lifespan of stroke-prone spontaneously hypertensive rats. 1651 28

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.
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PMID:Metabolic and genetic risk factors for migraine in children. 1668 13

Homocysteine is a thiol aminoacid synthesized during the metabolism of methionine. Increased plasma levels of homocysteine can be the result of mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine-beta synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR). Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or vitamin B12 (methylcobalamin), can induce hyperhomocysteinemia. Over the last decade, following in vitro and in vivo observations of a homocysteine-associated vascular pathology, convincing epidemiological evidence has been gathered on the relation between moderate elevation of plasma homocysteine and vascular disease, including cerebral ischemia. However, causality has yet to be established. The association between homocysteine and ischemic stroke might be a spurious epidemiological finding because of confounding or it might reflect reverse causality. If this is the case, elevated levels of plasma homocysteine should be interpreted as an epiphenomenon secondary to the vascular disease itself. Thus, whether lowering homocysteine concentration prevents cerebral ischemia remains to be determined. The only method to answer the question of the causal relation between homocysteine and ischemic stroke is by intervention trials in which patients at high vascular risk, such as those who have had a recent cerebral ischemic event are randomly allocated to placebo or homocysteine-lowering multivitamin therapy, and followed prospectively. Some of these randomized controlled trials are currently ongoing. Their results should hopefully resolve the issue in the next future.
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PMID:Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. 1730 30

Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke.
J Stroke Cerebrovasc Dis
PMID:Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients. 1790 48

Methylenetetrahydrofolate reductase (MTHFR) is a vital enzyme catalyzing the nicotinamide adenine dinucleotide phosphate (NADPH) linked reduction of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which serves as cofactor in methylation of homocysteine to methionine. Three clinically important mutations of the MTHFR gene namely C677T, A1298C, and T1317C are reported to be associated with various pathological conditions. The present study deals with the screening of C677T mutation among two endogamous groups viz. Ahirs and Jats of Haryana (India). The mutation is reported to be significantly associated with thrombosis, hypertension, stroke and myocardial infraction, neural tube defects (NTDs), and recurrent pregnancy loss. The T allele among Jats is found to be more frequent (0.06) than Ahirs (0.03). Moreover, the Jats population shows a significant deviation from Hardy-Weinberg equilibrium with respect to C677T mutation. This could probably be due to some selection pressure operating in the population.
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PMID:MTHFR C677T polymorphisms among the Ahirs and Jats of Haryana (India). 1795 61


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