Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent publicity surrounding disappointing results of clinical trials of homocysteine lowering has led to the claim that 'homocysteine is dead'. However, there is strong evidence that elevated plasma total homocysteine is an important independent risk factor, and the highly plausible biological rationale is the following: total homocysteine increases coagulation, impairs endothelial function, increases oxidative stress and low density lipoprotein oxidation, and treatment with vitamins reverses these effects and halts progression of carotid plaque. Some studies have shown clinical benefit of vitamin therapy in coronary angioplasty and peripheral vascular disease. It has recently become apparent that vitamin B12 absorption is impaired in the elderly, and that metabolic B12 deficiency is much commoner than would be appreciated by statistical definitions of 'normal' serum B12; higher doses of B12 and perhaps other therapies such as betaine and thiols may be needed to achieve adequate reductions of total homocysteine. It remains likely that effective lowering of total homocysteine will reduce stroke and other vascular events.
Int J Stroke 2006 Nov
PMID:Homocysteine and stroke prevention: have the trials settled the issue? 1870 27

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.
 ...
PMID:Public health significance of elevated homocysteine. 1870 86

The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.
 ...
PMID:Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. 1930 62

Brain injury from ischemic stroke can be devastating, but full brain restoration is feasible. Time until treatment is critical; rapid rate of injury progression, logistical and personnel constraints on neurological and cardiovascular assessment, limitations of recombinant tissue plasminogen activator (rtPA) for thrombolysis, anticoagulation and antiplatelet interventions, and neuroprotection all affect outcome. Promising acute neuroprotectant measures include albumin, magnesium, and hypothermia. Long-term hyperbaric oxygen therapy (HBOT) is safe and holds great promise. Eicosanoid and cytokine down-regulation by omega-3 nutrients docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may help quench stroke inflammation. C-reactive protein (CRP), an inflammatory biomarker and stroke-recurrence predictor, responds favorably to krill oil (a phospholipid-DHA/EPA-astaxanthin complex). High homocysteine (Hcy) is a proven predictor of stroke recurrence and responds to folic acid and vitamin B12. Vitamin E may lower recurrence for individuals experiencing high oxidative stress. Citicoline shows promise for acute neuroprotection. Glycerophosphocholine (GPC) is neuroprotective and supports neuroplasticity via nerve growth factor (NGF) receptors. Stem cells have shown promise for neuronal restoration in randomized trials. Endogenous brain stem cells can migrate to an ischemic injury zone; exogenous stem cells once transplanted can migrate (home) to the stroke lesion and provide trophic support for cortical neuroplasticity. The hematopoietic growth factors erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) have shown promise in preliminary trials, with manageable adverse effects. Physical and mental exercises, including constraint-induced movement therapy (CIMT) and interactive learning aids, further support brain restoration following ischemic stroke. Brain plasticity underpins the function-driven brain restoration that can occur following stroke.
 ...
PMID:Integrated brain restoration after ischemic stroke--medical management, risk factors, nutrients, and other interventions for managing inflammation and enhancing brain plasticity. 1936 91

Blood levels of total homocysteine (tHcy), cysteine (Cys), total and reduced glutathione (tGSH and rGSH), folic acid (FA), and vitamin B12 (B12) change during ischemic stroke as accompaniment of the tissue damage. The relationship between these changes remains scantly investigated. We evaluated the variation of these molecules in the 48 h after acute large artery atherothrombotic stroke (LAAS) and searched for the presence of matched variation of them. The study involved 50 subjects affected by acute LAAS and 49 healthy controls. Plasma levels of tHcy and Cys were significantly higher and serum levels of FA and B12 and plasma levels of rGSH were significantly lower in the patients than in the control group. Acute LAAS was associated with increased Hcy-decreased tGSH and decreased FA/tGSH. Pathways involved in cellular stress and in tissue repair are activated during acute LAAS.
 ...
PMID:Blood levels of homocysteine, cysteine, glutathione, folic acid, and vitamin B12 in the acute phase of atherothrombotic stroke. 1948 86

In the present review concerning stroke, we evaluate the roles of B vitamins, homocysteine and antioxidant vitamins. Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. Several studies have reported important benefits on reducing the risk of stroke and improving the post-stroke-associated functional declines in patients who ate foods rich in micronutrients, including B vitamins and antioxidant vitamins E and C. Folic acid, vitamin B6 and vitamin B12 are all cofactors in homocysteine metabolism. Growing interest has been paid to hyperhomocysteinaemia as a risk factor for CVD. Hyperhomocysteinaemia has been linked to inadequate intake of vitamins, particularly to B-group vitamins and therefore may be amenable to nutritional intervention. Hence, poor dietary intake of folate, vitamin B6 and vitamin B12 are associated with increased risk of stroke. Elevated consumption of fruits and vegetables appears to protect against stroke. Antioxidant nutrients have important roles in cell function and have been implicated in processes associated with ageing, including vascular, inflammatory and neurological damage. Plasma vitamin E and C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. After reviewing the observational and intervention studies, there is an incomplete understanding of mechanisms and some conflicting findings; therefore the available evidence is insufficient to recommend the routine use of B vitamins, vitamin E and vitamin C for the prevention of stroke. A better understanding of mechanisms, along with well-designed controlled clinical trials will allow further progress in this area.
 ...
PMID:Stroke: roles of B vitamins, homocysteine and antioxidants. 1955 18

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function.
 ...
PMID:Hyperhomocysteinemia in uremia--a red flag in a disrupted circuit. 1970 80

In Europe, neuropsychiatric diseases currently make up approximately a third of the total burden of disease. In 2004, 27% of the overall population was affected by at least one of the most frequent neuropsychiatric diseases such as Alzheimer's dementia, Parkinson's disease, stroke or depression. The annual costs of care exceed those of cancer, cardiovascular conditions and diabetes. In order to delay the onset or course of neurodegenerative diseases, the available potential should be utilized. As well as improving quality of life of patients and relatives, this may reduce the great financial burden caused by neurodegenerative disorders. However, the availability of established drugs or therapeutic agents is very limited. This paper reviews the state of current knowledge as to how homocysteine metabolism is relevant for neurodegenerative and other neuropsychiatric diseases, with particular emphasis on the evidence for prophylactic and therapeutic strategies. In the European countries, many people do not take the recommended daily minimum amount of folate and vitamin B12. Deficiency of these vitamins and secondary changes in the concentrations of associated metabolites, such as methylmalonic acid and homocysteine, may contribute to the onset and progression of neuropsychiatric diseases. This paper reviews the evidence regarding whether substitution of folate and vitamin B12 is beneficial, for example, in cerebrovascular disease, dementia and depression.
 ...
PMID:Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations. 1976 53

Hyperhomocysteinemia is generally acknowledged as a treatable risk factor for atherotrombotic diseases, but a causal relationship between both is not yet definitively established. Hyperhomocysteinemia originates from a deviation in the methionine-homocysteine metabolism including disturbances of enzymes, vitamin deficiencies and different other factors. Observational studies, genetic polymorphism studies and several meta-analyses implicate already a causal relation between homocysteine and cerebrovascular diseases. It is useful to determine homocysteine levels for stroke who present no clue for vascular disease and thrombosis, who have an ischemic stroke at a young age and who have a family history of premature atherosclerosis. Because of the low cost and safety of the therapy, the American Heart and Stroke Association advises to treat patients with a stroke and hyperhomocysteinemia daily with 0,4 mg folic acid, 2,4 microg vitamin B12 and 1,7 mg vitamin B6. A significant benefit in secondary prevention is not yet proven. The results of larger follow-up trials have to be published.
 ...
PMID:Ischemic stroke and hyperhomocysteinemia: truth or myth? 1990 11

High blood pressure (BP) and elevated homocysteine are reported as independent risk factors for CVD and stroke in particular. The main genetic determinant of homocysteine concentrations is homozygosity (TT genotype) for the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, typically found in approximately 10% of Western populations. The B-vitamins folate, vitamin B12 and vitamin B6 are the main nutritional determinants of homocysteine, with riboflavin more recently identified as a potent modulator specifically in individuals with the TT genotype. Although observational studies have reported associations between homocysteine and BP, B-vitamin intervention studies have shown little or no BP response despite decreases in homocysteine. Such studies, however, have not considered the MTHFR C677T polymorphism, which has been shown to be associated with BP. It has been shown for the first time that riboflavin is an important determinant of BP specifically in individuals with the TT genotype. Research generally suggests that 24 h ambulatory BP monitoring provides a more accurate measure of BP than casual measurements and its use in future studies may also provide important insights into the relationship between the MTHFR polymorphism and BP. Further research is also required to investigate the association between specific B-vitamins and BP in individuals with different MTHFR genotypes in order to confirm whether any genetic predisposition to hypertension is correctable by B-vitamin intervention. The present review will investigate the evidence linking the MTHFR C677T polymorphism to BP and the potential modulating role of B-vitamins.
 ...
PMID:Postgraduate Symposium: The MTHFR C677T polymorphism, B-vitamins and blood pressure. 1995 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>