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)

We report a 67-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), successfully treated with eicosapentaenoic acid ethyl ester (EPA-E) for about eight months. He showed bilateral auditory disturbance and slowly progressive gait ataxia at age 50 during treatment of diabetes mellitus (DM) with subcutaneous injection of insulin since age 29. At age 58 he manifested an acute hemiparesis of right extremities for one week with no abnormal findings on neuroradiological examinations. A permanent pacemaker was implanted at age 61 to treat frequent syncopal attacks due to complete atrioventricular block. On admission to our hospital, neurological examinations revealed dementia, auditory disturbance, severe cerebellar ataxia and mild atrophy of proximal muscles with systemic hyporeflexia. Based on a point mutation in position 3243 of mitochondrial DNA, he was diagnosed as having MELAS with severe DM, auditory disturbance and cardiac conduction block. After initiation of treatment with EPA-E at a dose of 2,700 mg/day he showed temporarily an improvement in auditory disturbance, blood glucose control and cerebellar ataxia. In objective evaluations for cerebellar ataxia, we could find significant decreases in times for 20 m walking and heel-knee patting in the ninth month, and in time for tracing of a whirl from the third to the ninth month, compared with those before treatment of EPA-E (p < 0.0001). Because EPA-E is taken into mitochondrial membranes and activates electron transmission enzyme complexes, it might be a candidate for therapy of mitochondrial encephalomyopathy, including MELAS.
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PMID:[A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), showing temporary improvement during the treatment with eicosapentaenoic acid ethyl ester]. 1199 86

The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model of malignant hypertension which lead to secondary alterations of the extracellular matrix. Our aim was to determine ACE-inhibitor related changes of proteases involved in the reconstruction of the extracellular matrix in the brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated with either an antihypertensive dose of ramipril or placebo for 6 months. Brain tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP-9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p < 0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25% in the basal ganglia (p < 0.0001 each). No differences were observed in the amount of TIMP-1 or TIMP-2. These findings provide new insights into the biochemical mechanisms underlying extracellular matrix proliferation and its modulation by ACE inhibitors. Therapeutic alterations that influence the proteolytic systems might prove important in the prevention of extracellular matrix accumulation and secondary microvascular vessel wall changes.
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PMID:ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats. 1572 Dec 22

The aim of the study was to determine serum levels of selected matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs) in the acute phase of different stroke types subdivided according to the Oxfordshire Community Stroke Project (OCSP) classification and the possibility of discriminating stroke types according to their levels. The study included 126 patients with acute stroke within the first 24 h of symptom onset, and 124 healthy volunteers. The stroke group had lower MMP-2 concentrations and MMP-2/TIMP-2 ratios (p<0.001) but higher TIMP-2 (p<0.001) than controls. The level of MMP-9 and the MMP-9/TIMP-1 ratio were higher in patients with total anterior circulation infarct (TACI) than in patients with other stroke subtypes according to OCSP classification (p=0.0019, p=0.0065, respectively) or in controls (p<0.0001, p=0.0024, respectively). A negative correlation of MMP-2 levels with MMP-9 and MMP-9/TIMP-1 ratio was recorded in all stroke subtypes except for TACI. Receiver operating characteristic analysis showed similar discriminating power for MMP-9 levels and Barthel index in the differential diagnosis of TACI. High MMP-9/TIMP-1 ratio (odds ratio 3.263) was associated with TACI. Our results demonstrate that the MMP-9/TIMP-1 ratio may provide information to help in assessing stroke patients in the future as a baseline biomarker of infarct extent.
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PMID:Matrix metalloproteinases and their inhibitors in different acute stroke subtypes. 1659 37

Due to the large population and high levels of motorized-vehicle exhaust emissions, motorcycle emissions make an important contribution to total emissions in Taiwan, ROC. Aiming to reduce the air pollution generated by these motorcycles, the Taiwan Environmental Protection Administration (TEPA) has maintained an enforced inspection and maintenance (I/M) program for in-use motorcycles since 1996. This report explores the effects of engine type, engine size, engine age, and manufacturers of in-use motorcycles on CO/HC emissions in I/M testing data during the period of 1996-2002 in the Central Air Quality Basin of Taiwan. Additionally, geographical characteristics and failure rates of motorcycles are analyzed. The results indicate that the age, size, and type of engine, and the manufacturers of motorcycles all play a significant role in determining I/M emission test results. The findings also show that two-stroke motorcycles emitted approximately ten times greater HC than those of four-stroke motorcycles. CO/HC test emissions increase with a decrease in engine size, HC test emissions contributed by Yamaha and other manufacturers being the highest. Although CO/HC test emissions generally increase with the age of the motorcycle, older motorcycles do not contribute significantly to total emissions due to the small number of older motorcycles. It was observed that CO/HC test emissions depend on driving patterns, geographical location, and inspection rates of motorcycles. The failure rate due to CO is nearly four times greater than that of HC, and the older and smaller-engine-size motorcycles obtain greater failure rates. These statistical findings can also provide the EPA of Taiwan or other Asian countries with useful information for formulating better environmental strategies to manage motorcycles effectively.
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PMID:Test emission characteristics of motorcycles in Central Taiwan. 1664 44

MMP-9 plays an important role in the pathogenesis of AIS and predicts haemorrhagic transformation of the ischaemic focus. The aim of our study was to analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1) levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastatin) affects the MMP-9/TIMP-1 ratio value. Fifty patients with AIS were randomly divided into two groups: Group I (N = 25) treated with 40 mg/day with simvastatin within 24 hours after the onset of stroke and Group II (N = 25) non-treated with statin. To evaluate MMP-9 and TIMP-1 serum levels, the ELISA method was used. The serum MMP-9 level was significantly elevated on the 7th day of stroke in both groups (from 668 to 862 ng/ml and 670 to 855 ng/ml, respectively, in Group I and II). The serum TIMP-1 level was also elevated on the 7th day of stroke in both groups but the results were not significant. The MMP-9/TIMP-1 ratio was elevated on the 7th day of stroke in both groups, but the result was significant only in the Group II (P < 0.01). These findings indicate that simvastatin given during 24 hours after the onset of stroke could have an influence on the MMP-9/TIMP-1 ratio during AIS.
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PMID:Simvastatin could prevent increase of the serum MMP-9/TIMP-1 ratio in acute ischaemic stroke. 1718 95

The treatment of hyperlipidemia is aimed at preventing cardiovascular disease (CVD) and coronary heart disease (CHD). As the incidence of CHD in Japan is about one-third lower and that of stroke is two-fold higher compared to Western countries, and the doses of lipid-lowering drugs used in foreign randomized controlled clinical trials (RCTs) are much higher than in general use in Japan, it remains unclear whether the results of RCTs conducted in Western countries could be extrapolated to Japanese patients. Recently, two major large-scale, prospective, RCTs in Japanese hypercholesterolmic patients, the Management of Elevated Cholesterol in the Primary Prevention of Adult Japanese (MEGA) study and the Japan EPA Lipid Intervention Study (JELIS), have been reported. Japanese epidemiological studies and Japanese clinical studies are reviewed. The evidence suggests that hypercholesterolemia, hypertriglyceridemia, and low HDL-cholesterol are strongly associated with increased CHD risk. Lipid-lowering medication shows beneficial effects even in low-risk populations; however, the data did not support that lower cholesterol is better. The safety and efficacy of hyperlipidemia treatment in Japanese patients are discussed.
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PMID:Treatment of hyperlipidemia from Japanese evidence. 1719 91

The blood-brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Oxidative stress is a major underlying cause of neurodegenerative and neuroinflammatory disorders and BBB injury associated with them. Using human BMVEC grown on porous membranes covered with basement membrane (BM) matrix (BBB models), we demonstrated that reactive oxygen species (ROS) augmented permeability and monocyte migration across BBB. ROS activated matrix metalloproteinases (MMP-1, -2, and -9) and decreased tissue inhibitors of MMPs (TIMP-1 and -2) in a protein tyrosine kinase (PTK)-dependent manner. Increase in MMPs and PTK activities paralleled degradation of BM protein and enhanced tyrosine phosphorylation of tight junction (TJ) protein. These effects and enhanced permeability/monocyte migration were prevented by inhibitors of MMPs, PTKs, or antioxidant suggesting that oxidative stress caused BBB injury via degradation of BM protein by activated MMPs and by PTK-mediated TJ protein phosphorylation. These findings point to new therapeutic interventions ameliorating BBB dysfunction in neurological disorders such as stroke or neuroinflammation.
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PMID:Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. 1725 Jun 80

Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20 : 5n-3) and DHA (22 : 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case-control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0.90 (95 % CI 0.73, 1.11) per meal per week). The risk in women differed significantly (P = 0.03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1.24 (95 % CI 1.01, 1.51) per meal per week). The corresponding risk in men for Hg was 0.99 (95 % CI 0.93, 1.06), and for the sum of proportions of EPA and DHA 1.08 (95 % CI 0.92, 1.28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.
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PMID:Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in northern Sweden. 1753 90

A major goal of the second International Workshop on "Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders" was the identification of important future research areas that would lead to accelerated and systematic progress in the field. Major themes identified for future research include the following: (1) Rigorous research protocols for fatty acid (FA) studies should be established to overcome errors introduced by small differences in chain length and degree of unsaturation. (2) Using cellular integration models consisting of endothelial cells, astrocytes, and neurons, investigation of functional lipidomics, cell-specific signaling by lipids, and nutritional considerations should be undertaken. (3) Educational programs should be undertaken for women of childbearing age on the health benefits of omega3 long chain (LC) polyunsaturated fatty acids (PUFA) from fish consumption vs risks of mercury in fish. (4) Studies of the "flip-flop" model of passive diffusion should be extended to include other quantitative measures, such as the sizes of different fatty acid pools. (5) Investigations to establish physiologic roles and concentrations of omega3 LC-PUFA in various compartments of the brain should be undertaken. (6) Further studies should be carried out to illuminate the role and behavior of tight junctions in the microvascular endothelium of the blood-brain barrier and astrocytes, with emphasis on developing new LC-PUFA and lipid-based carriers of biomolecules across this barrier. (7) Roles and localization of very low density lipoproteins, low density lipoprotein (LDL), and the LDL receptor in the brain and their interactions with omega3 LC-PUFA, cholesterol, apolipoprotein E1-4, and their derivatives in Alzheimer's disease (AD) should be assessed. (8) Investigation of intraneuronal synthesis of DHA and its effects on signal transduction, apoptosis, and neurite growth stimulation should be undertaken. (9) Nutrition-based behavioral affects of EPA and DHA, particularly with respect to the omega6:omega3 FA ratio, gene regulation, neurodevelopment, and conversion to bioactive molecules by cyclooxygenases (COX) and lipoxygenase, should be explored. (10) Further assessment of brain lipid metabolism and neurodevelopment should be performed in DHA-deficient rodent models, including the use of imaging techniques. (11) Potential toxic effects of COX overexpression and the possible consequences of DHA over-supplementation in various neurological and neurodevelopmental disorders should be characterized. (12) The relationship between LC-PUFA, stroke, and AD should be clarified, and neurogenetic metabolic diseases that could benefit from supplementation with omega3 LC-PUFA such as DHA should be identified.
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PMID:Brain uptake and utilization of fatty acids, lipids & lipoproteins: recommendations for future research. 1790 59

Blood-brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Activation of matrix metalloproteinases (MMPs) and alteration of basement membrane (BM) associated with BBB injury was documented in stroke patients. While chronic alcoholism is a risk factor for developing stroke, underlying mechanisms are not well understood. We hypothesized that ethanol (EtOH)-induced protein tyrosine kinase (PTK) signaling resulted a loss of BBB integrity via MMPs activation and degradation of BM component, collagen IV. Treatment of BMVEC with EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity. Enhanced PTK activity after EtOH exposure correlated with increased phosphorylated proteins of selective receptor and nonreceptor PTKs. Up-regulation of MMPs activities and protein contents paralleled a decrease in collagen IV content, and inhibitors of EtOH metabolism, MMP-2 and -9, or PTK reversed all these effects. Using human BMVEC assembled into BBB models, we found that EtOH/AA diminished barrier tightness, augmented permeability, and monocyte migration across the BBB via activation of PTKs and MMPs. These findings suggest that alcohol associated BBB injury could be mediated by MMPs via BM protein degradation and could serve as a comorbidity factor for neurological disorders like stroke or neuroinflammation. Furthermore, our preliminary experiments indicated that human astrocytes secreted high levels of MMP-1 and -9 following exposure to EtOH, suggesting the role of BM protein degradation and BBB compromise as a result of glial activation by ethanol. These results provide better understanding of multifaceted effects of alcohol on the brain and could help develop new therapeutic interventions.
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PMID:Activation of protein tyrosine kinases and matrix metalloproteinases causes blood-brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse. 1794 53


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