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

Atherosclerosis is a chronic disease which involves the build up of cholesterol and fatty deposits within the arterial wall. This results in the narrowing of the vessel lumen, which eventually restricts blood flow to vital organs such as the heart and lungs. These events may culminate in a heart attack or stroke, the commonest causes of death in the U.K. population. In this paper we study the early stages of atherosclerosis which include the build up of cholesterol within subendothelial cells to form what is known as a fatty streak, the earliest identifiable evidence of atherosclerosis. The deposition of cholesterol is believed to be a consequence of oxidation of circulating cholesterol-rich lipoproteins, in particular low density lipoproteins (LDLs). Via a mathematical model we investigate this process of oxidation within the context of an in vitro framework. We first recreate existing experimental results and then extend the model to investigate phenomenon not studied by current experimental protocols. We find that the model displays hysteresis which reveals some interesting insights into possible in vivo events. Mathematical analysis of this behaviour predicts that vitamin E supplementation is not as beneficial as high density lipoproteins (HDLs) and vitamin C. Furthermore, the scavenging of oxidants by HDL can provide an important first line of defence against LDL oxidation.
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PMID:Lipoprotein oxidation and its significance for atherosclerosis: a mathematical approach. 1186 38

During cerebral ischemia-reperfusion, the enhanced production of oxygen-derived free radicals contributes to neuronal death. The antioxidants alpha-lipoic acid and vitamin E have shown synergistic effects against lipid peroxidation by oxidant radicals in several pathological conditions. A thromboembolic stroke model in rats was used to analyze the effects of this mixture under two oral treatments: intensive and prophylactic. Neurological functions, glial reactivity and neuronal remodeling were assessed after experimental infarction. Neurological recovery was only found in the prophylactic group, and both antioxidant schemes produced down-regulation of astrocytic and microglial reactivity, as well as higher neuronal remodeling in the penumbra area, as compared with controls. The beneficial effects of this antioxidant mixture suggest that it may be valuable for the treatment of cerebral ischemia in humans.
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PMID:Beneficial effects of alpha-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodeling in the penumbra of the ischemic rat brain. 1187 66

This review discusses research methodology in the relation between diet and disease. Medical research can be divided into two types: complex research (the detailed study of disease mechanisms using such methods as biochemistry and molecular genetics) and simple research (the investigation of the factors that cause or prevent disease using methods such as epidemiology, intervention trials, and analagous studies on animals). Although complex research has received the bulk of resources, the large majority of our information of practical value has come from simple research. This general principle is illustrated in the area of diet and disease by examples from various areas: selenium, carotenoids, and cancer; vitamin E, omega-3 fatty acids, and coronary heart disease; dietary fat and obesity; dietary sodium and hypertension; and alcohol and stroke. Discussion then turns to aspects of the design of cohort (prospective) studies. Because of problems of sample size and relative lack of diversity, previous studies often failed to give clear-cut results. Suggestions are made concerning the design of cohort studies, notably the use of much larger numbers of subjects and with greater diversity in their diets. The problem of confounding also is discussed. Lifestyle factors often cluster together but cohort studies may not have fully unraveled this.
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PMID:Nutrition and disease: challenges of research design. 1193 52

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
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PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

Many neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimer's disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the AD-associated amyloid beta protein (Abeta) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chain-breaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including alpha-tocopherol (vitamin E) and 17beta-estradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine- and tryptophan-containing structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.
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PMID:Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. 1203 40

Caffeine is the most widely consumed behaviourally active substance in the western world. Neuroprotective effects of caffeine in low doses, chronically administered, have been shown in different experimental models. If caffeine intake could protect against neurodegeneration in Alzheimer's disease (AD), then higher levels of caffeine consumption in normal subjects as compared with AD patients should be detectable in the presumably long period before diagnosis when insidious pathogenic changes are taking place. A case-control study was used: cases were 54 patients with probable AD fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke and the AD and Related Disorders Association criteria, in a Dementia Clinics setting. Controls were 54 accompanying persons, cognitively normal, matched for age (+/-3 years) and sex. Patients with AD had an average daily caffeine intake of 73.9 +/- 97.9 mg during the 20 years that preceded diagnosis of AD, whereas the controls had an average daily caffeine intake of 198.7 +/- 135.7 mg during the corresponding 20 years of their lifetimes (P < 0.001, Wilcoxon signed ranks test). Using a logistic regression model, caffeine exposure during this period was found to be significantly inversely associated with AD (odds ratio=0.40, 95% confidence interval=0.25-0.67), whereas hypertension, diabetes, stroke, head trauma, smoking habits, alcohol consumption, non-steroid anti-inflammatory drugs, vitamin E, gastric disorders, heart disease, education and family history of dementia were not statistically significantly associated with AD. Caffeine intake was associated with a significantly lower risk for AD, independently of other possible confounding variables. These results, if confirmed with future prospective studies, may have a major impact on the prevention of AD.
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PMID:Does caffeine intake protect from Alzheimer's disease? 1209 22

Stroke is one of the major causes of morbidity and mortality in recent. Oxygen free radicals produced during cerebral infarction increases the damage to neurons. Superoxide dismutase (SOD) is the endogenous antioxidant enzyme that can effectively scavenge superoxide radicals. Catechin is a hydrophilic antioxidant usually existed in tea, fruits and vegetables. In the cultured rat brain astrocytes (RBA), the activity of SOD (both Cu, Zn-SOD and Mn-SOD subtypes) was markedly increased by incubation with catechin at low concentration (0.1 microM) for 2 days (short-term) and 7 days (long-term). This stimulatory effect of catechin was not related to the incubating concentration. Similar changes were also observed in the gene expression of SOD in RBA. The increase in quantity of SOD-messenger RNA was remarkable and seemed to be more obvious than the other antioxidants such as vitamin E. This result shows that catechin is an effective antioxidant to increase the activity of SOD in RBA which would be beneficial to neurons subjected to oxygen free radical damage.
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PMID:Effect of catechin on the activity and gene expression of superoxide dismutase in cultured rat brain astrocytes. 1214 26

Side-stream cigarette smoke (SSCS), a major component of secondhand smoke, induces reactive oxygen species, which promote oxidative damage in tissues and organs. Inflammatory cytokines play an important role in the pathogenesis of atherosclerosis and heart failure. The present 4-month study examined the effect of various chronic SSCS exposure levels on splenic inflammatory cytokine secretion, heart contractile function, and pathology at 60- and 120-min per day, 5 days per week, for a total of 16 weeks. Tissue vitamin E level and lipid peroxide production also were tested to estimate the oxidative stress. The study found that the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta, significantly increased in 120-min SSCS-exposed mice. Decreased stroke volume and increased peripheral arterial resistance were observed in mice exposed to 120-min SSCS per day. Heart pathology was only found in 120-min SSCS-exposed mice. Cardiac and hepatic antioxidant vitamin E levels were decreased as a result of oxidative stress. Hepatic lipid peroxides were increased upon 60-min SSCS exposure. The data also demonstrated that the cardiac alpha-tocopherol level has a strong correlation with stroke volume; splenic IL-1beta has a strong negative correlation with stroke volume; splenic TNF-alpha has a very strong negative correlation with stroke volume. In conclusion, SSCS exposure induced systemic inflammatory responses. SSCS exposure also accentuated systemic lipid peroxidation with depletion of cardiac and hepatic antioxidant vitamin E level. Finally, SSCS exposure at 120 min per day decreased stroke volume and increased vascular resistance. Systemic IL-1beta and TNF-alpha production are responsible for heart contractile dysfunction. Free radicals may be responsible for the progression to heart contractile dysfunction induced, in part, by SSCS. Oxidized lipoprotein could contribute to the vascular functional changes. Exploring the mechanism of vascular dysfunction in mice is warranted. A more precise quantification of the smoking exposure dose in mice needs to be determined as well.
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PMID:Side-stream cigarette smoke induces dose-response in systemic inflammatory cytokine production and oxidative stress. 1232 64

The Heart Outcomes Prevention Evaluation (HOPE) study, an international randomized trial, was designed to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril and vitamin E in patients at high risk for cardiovascular events. The study did not detect any cardiovascular benefit or harm using vitamin E. Results for the vitamin E arm are not discussed here. Of 9541 patients, 3577 with diabetes received either ramipril (10 mg) or placebo. Among these patients, ramipril use was associated with a significant 25% reduction in risk for the composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death after a median follow-up period of 4.5 years. This benefit was independent of any blood pressure-lowering effect. The Microalbuminuria, Cardiovascular, and Renal Outcomes in HOPE (MICRO-HOPE) substudy in this patient population showed that ramipril treatment was associated with a decreased risk of development of overt nephropathy. Use of a composite measure of microvascular complications also suggested a protective effect of ramipril treatment. An interesting finding in the HOPE study is that ramipril treatment was associated with a significant 34% reduction in new diagnoses of diabetes. The possibility that ACE inhibitor treatment with ramipril may prevent new diabetes in non-diabetic patients at high risk of the disease is to be examined prospectively in the Diabetes Reduction Assessment with ramipril and rosiglitazone (DREAM) trial.
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PMID:Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO-HOPE. 1232 91

Aggressive treatment of atherosclerotic risk factors can substantially reduce stroke risk in patients with a history of stroke or transient ischemic attack. Data from several recent large clinical trials provide convincing evidence of benefit for a number of specific therapies directed at this population. The authors recommend treatment with ramipril alone or perindopril plus indapamide regardless of blood pressure, provided there is no contraindication. For patients already taking a different angiotensin- converting enzyme (ACE) inhibitor, the authors do not routinely switch agents. The authors recommend use of simvastatin 40 mg per day in patients with a total cholesterol level of 135 mg/dL or greater, provided no contraindication exists. The authors also recommend consideration of gemfibrozil in patients with isolated low high- density lipoprotein levels. In patients with diabetes mellitus, tight glycemic control has not been shown to reduce macrovascular complications such as stroke, but does reduce microvascular complications. However, diabetics should receive especially aggressive treatment of other vascular risk factors. There is no role for post-menopausal hormone replacement therapy in prevention of stroke. Weight loss for overweight patients, regular exercise, and a diet rich in fruits, vegetables, cereals, and fish, as well as low in fat and cholesterol, should be a standard recommendation for this group of patients. Treatment with folic acid, B(6), and B(12) for patients with elevated homocysteine appears rational, though this is unproven. However, there is no benefit to vitamin E, vitamin C, or beta-carotene supplementation. Smokers should stop. For every 43 smokers who quit, one stroke is prevented. Moderate consumption of alcohol (one to two drinks a day) may be beneficial, but heavy alcohol use (more than five drinks a day) increases stroke risk.
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PMID:Atherosclerotic Risk Factors in Patients with Ischemic Cerebrovascular Disease. 1235 71


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