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

Hyperhomocysteinemia, caused by a lack of cystathionine beta synthase (CBS), leads to elevated plasma concentrations of homocysteine. This is a common risk factor for atherosclerosis, stroke, and possibly neurodegenerative diseases. However, the mechanisms that link hyperhomocysteinemia due to CBS deficiency to these diseases are still unknown. Early biochemical studies describe developmental and adult patterns of transsulfuration and CBS expression in a variety of species. However, there is incomplete knowledge about the regional and cellular expression pattern of CBS, notably in the brain. To complete the previous data, we used in situ hybridization and Northern blotting to characterize the spatial and temporal patterns of Cbs gene expression during mouse development. In the early stages of development, the Cbs gene was expressed only in the liver and in the skeletal, cardiac, and nervous systems. The expression declined in the nervous system in the late embryonic stages, whereas it increased in the brain after birth, peaking during cerebellar development. In the adult brain, expression was strongest in the Purkinje cell layer and in the hippocampus. Immunohistochemical analyses showed that the CBS protein was localized in most areas of the brain but predominantly in the cell bodies and neuronal processes of Purkinje cells and Ammon's horn neurons.
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PMID:Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain. 1258 64

Atherosclerosis is an important medical problem of the 21st century, but traditional risk factors could only account for 50% of the problem. Hyperhomocysteinemia is emerging as an independent atherosclerosis risk factor, associated with folate deficiency, renal failure, and relative deficiency of MTHFR (C677T polymorphism) or other enzymes depending on gender, age, and smoking status. Hyperhomocysteinemia has been reported to occur in 11-22% of western people, in 3-5% of normal asymptomatic Chinese subjects aged 18-70 years in Hong Kong, Macau, Sydney, and San Francisco, 23-36% of Chinese in Hong Kong with premature coronary artery disease, and 29% of a nonselective series of coronary subjects in Hong Kong. Evidence is accumulating that documents its associations with atherosclerosis disease in both case-control observations and prospective cohort studies, in vitro experiments, and in vivo experimental models in both animals and human subjects, as well as the successful improvement by homocysteine-lowering of endothelial function as surrogate atherosclerosis endpoints in asymptomatic human and coronary patients (secondary prevention). A number of large scale homocysteine-lowering trials are currently underway for stroke and heart attacks prevention. Collectively these trials will include more than 65,000 patients at high-risk for cardiovascular and stroke events, and should provide a reliable evidence-base for prevention.
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PMID:Homocysteine, endothelial dysfunction, and coronary artery disease: emerging strategy for secondary prevention. 1263 May 44

Moderate hyperhomocysteinemia is associated with several diseases, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, and spina bifida. However, the mechanisms for their pathogenesis are unknown but could involve the interaction of homocysteine or its metabolites with molecular targets such as neurotransmitter receptors, channels, or transporters. We discovered that L-homocysteine sulfinic acid (L-HCSA), L-homocysteic acid, L-cysteine sulfinic acid, and L-cysteic acid are potent and effective agonists at several rat metabotropic glutamate receptors (mGluRs). These acidic homocysteine derivatives 1) stimulated phosphoinositide hydrolysis in the cells stably expressing the mGluR1, mGluR5, or mGluR8 (plus Galpha(qi9)) and 2) inhibited the forskolin-induced cAMP accumulation in the cells stably expressing mGluR2, mGluR4, or mGluR6, with different potencies and efficacies depending on receptor subtypes. Of the four compounds, L-HCSA is the most potent agonist at mGluR1, mGluR2, mGluR4, mGluR5, mGluR6, and mGluR8. The effects of the four agonists were selective for mGluRs because activity was not discovered when L-HCSA and several other homocysteine derivatives were screened against a large panel of cloned neurotransmitter receptors, channels, and transporters. These findings imply that mGluRs are candidate G-protein-coupled receptors for mediating the intracellular signaling events induced by acidic homocysteine derivatives. The relevance of these findings for the role of mGluRs in the pathogenesis of homocysteine-mediated phenomena is discussed.
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PMID:L-homocysteine sulfinic acid and other acidic homocysteine derivatives are potent and selective metabotropic glutamate receptor agonists. 1264 61

Vascular dementia (VaD) is the second-most-common cause of dementia in the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and hyperhomocysteinemia.
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PMID:Vascular dementia: distinguishing characteristics, treatment, and prevention. 1280 86

The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocysteine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascular disease.
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PMID:Study on the relationship between plasma homocysteine and acute cerebral vascular disease. 1284 Sep 27

The etiological role of hyperhomocysteinemia in the origin of neural-tube defects was proved, therefore a mandatory flour folic acid fortification program was introduced in the USA since January 1, 1998. In Hungary one kind of breads was fortified with folic acid, vitamin B12 and vitamin B6. The Hungarian randomised controlled trials of periconceptional folic acid containing micronutrient-combination supplementation also indicated a reduction in the occurrence of congenital cardiovascular malformations, urinary tract's defects and congenital limb deficiencies and these findings were confirmed by US teams. Recent studies showed a positive association between cardiovascular diseases and hyperhomocysteinemia as well, thus it is considered as an independent etiological factor in the pathogenesis of ischemic heart diseases, stroke, deep vein thrombosis, in addition of vascular diseases in the placenta during pregnancy. Other studies showed that hyperhomocysteinemia is more prevalent in demented patients and in persons with impaired cognitive performance. Some association was also found between hyperhomocysteinemia and cancers (e.g. colon). There is strong evidence that four vitamins B, such as vitamin B11 (folate-folic acid), vitamin B12, B2 and B6 can reduce the level of serum homocysteine and subsequently neural-tube defects. In addition the results of intervention studies indicated a protective effect of folic acid and other vitamins B for some other congenital abnormalities, cardiovascular diseases, senile dementia and cancers. The flour fortification with these water-soluble vitamins B is appropriate for an effective public health program for the primary prevention of these hyperhomocysteinemia-related disorders. There is no real risk for side effects on the basis of available US, Canadian and Hungarian experiences. In conclusion an urgent task is to introduce a mandatory flour fortification program in Hungary.
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PMID:[Public health control of hyperhomocysteinemia and its consequences]. 1462 40

Measurement of total homocysteine (tHcy) in healthy and diseased children has documented the utility of this marker in pediatric research and diagnostics. This article focuses on novel data obtained in infants, children and adolescents, with emphasis on cobalamin status in infants. In children, determinants of plasma tHcy are similar to those established in adults, and include age, gender, nutrition, B-vitamin status, and some drugs interfering with B-vitamin function. In infants (age < 1 year), tHcy is moderately elevated and related to serum cobalamin, whereas in older children and throughout childhood, plasma tHcy is low (about 60% of adult levels), and folate status becomes a strong tHcy determinant. As in adults, hyperhomocysteinemia in childhood is a risk factor for stroke, and folate-responsive hyperhomocysteinemia has been detected in children with renal failure. tHcy seems to be a sensitive indicator of folate deficiency in children on a poor diet, in HIV-infected children, and in children treated with anti-folate drugs. In children at increased risk of cobalamin deficiency, which includes children born to vegetarian mothers or children in developing countries on a poor diet, tHcy and methylmalonic acid are responsive indicators of a deficiency state. In newborns and infants born to mothers with an adequate nutrition, there are consistent observations of low cobalamin, elevated tHcy and methylmalonic acid, and reduction of both metabolites by cobalamin supplementation. These data have raised the question whether cobalamin deficiency may be widespread and undetected in babies born to non-vegetarian women on a Westernized diet.
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PMID:Hyperhomocysteinemia and B-vitamin deficiencies in infants and children. 1465 20

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (ischemic disease, such as stroke and myocardial infarction, and arterial and venous thrombotic events) in the general population. We can assume that the association is causal, based on the example of homocystinuria, and on the evidence put forward by several basic science and epidemiological studies; however, the results of large intervention trials, which will grant further support to this hypothesis, are not yet available. In addition, the mechanisms underlying this relationship, and also explaining the several toxic effects of homocysteine, related or not to cardiovascular disease, are unclear. Oxidation is one of the most favored postulated mechanisms; others are nitrosylation, acylation, and hypomethylation. Regarding the relative importance of these mechanisms, each of these hold pros and cons, and these are weighed in order to propose a balance of evidence.
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PMID:Homocysteine and oxidative stress. 1466 Nov

Hyperhomocysteinemia is an emerging risk factor for cardiovascular disease and stroke. The mechanisms underlying the pathophysiology of hyperhomocysteinemia are not completely defined, but endothelial dysfunction resulting from impaired bioavailability of nitric oxide is a consistent finding in experimental models. One potential mechanism for decreased nitric oxide bioavailability is inhibition of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA have been found in association with hyperhomocysteinemia and endothelial dysfunction in both animals and humans. Additional studies are required to determine the mechanisms by which ADMA accumulates in hyperhomocysteinemia and to define the importance of ADMA in the endothelial dysfunction of hyperhomocysteinemia in vivo.
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PMID:Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA. 1466 4

Very little is known about any interaction between patent foramen ovale (PFO) and various hypercoagulable disorders that have been associated with cryptogenic stroke. Percutaneous PFO closure for secondary prevention of paradoxical thromboembolization is receiving increasing attention. Hypercoagulability may affect the potential risks and expected benefits of percutaneous PFO closure. Consecutive patients undergoing percutaneous PFO closure at a single center were screened for the presence of antiphospholipid antibodies, elevated lipoprotein(a), hyperhomocysteinemia, and dysfibrinogenemia. Sixteen of 34 patients (47%) with complete arterial hypercoagulability screening had laboratory evidence of arterial hypercoagulability. Thirteen of these patients (38%) had antiphospholipid antibodies. Antiphospholipid antibodies appear to be common in patients referred for percutaneous PFO closure for secondary prevention of systemic thromboembolic events. Thorough testing based on established recommendations is warranted. Further studies are needed regarding the interaction between PFO and various hypercoagulable disorders that have been associated with cryptogenic stroke.
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PMID:Antiphospholipid antibodies are common in patients referred for percutaneous patent foramen ovale closure. 1469 71


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