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

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
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PMID:Anti-atherosclerotic effects of vitamin E--myth or reality? 1509 Feb 61

We previously reported that vitamin E prevents apoptosis in neurons during cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats (SHRSP). In this paper, we analyzed the effects of antihypertensives as well as vitamin E, which were added to neuron cultures after reoxygenation (20% O2) following hypoxia (1% O2). When added after hypoxia before reoxygenation, vitamin E conferred significant protection to neuronal cells. It was also shown that vitamin E conferred complete protection from neural cell death when added hypoxia and again before reoxygenation. At higher concentrations of vitamin E, strong neuroprotection was observed. Moreover, we verified that pretreatment with either amlodipine, carvedilol or dipyridamole consistently prevented cell death during hypoxia and reoxygenation (H/R). On the other hand, nilvadipine, a dihydropyridine-type calcium entry blocker, had no apparent effect on neuroprotection during H/R. The order of neuroprotective potency was vitamin E > dipyridamole > carvedilol > or = amlodipine > nilvadipine. In parallel experiments, we examined whether these antihypertensive agents were more effective when combined with vitamin E and dipyridamole. The results suggested that in our in vitro model system, antioxidants were the most important agents for the reduction of oxygen-free radical damage in cortical neurons. These findings suggest that amlodipine and carvedilol, with their antioxidant properties and antihypertensive activity, would be useful to inhibit neuronal cell death in the treatment of cerebrovascular stroke and neurodegenerative diseases in hypertensive patients.
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PMID:Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats. 1512 85

Numerous observational studies showed associations of antioxidants (vitamins C and E) and folate intake with a reduced risk of cardiovascular disease, but randomized controlled clinical trials have generally not supported this hypothesis. The objective of this study was to investigate the effects of a daily dosage of 1000 mg vitamin C, 800 mg vitamin E, and 10 mg folate on markers of vascular function in 31 young healthy male adults. Cardiovascular values after a 12-week vitamin (14 subjects) or placebo (17 subjects) intervention were compared to baseline values. Cardiovascular parameters (blood pressure, stroke volume, heart rate, cardiac output, vascular resistance, arterial compliance) were measured continuously after an overnight fast under controlled circumstances with a Finometer device. Our main finding was a significant decrease (p = 0.03) in systolic blood pressure in the experimental group. No statistically significant changes were observed within other cardiovascular variables of the experimental group, but possible beneficial decreases in diastolic blood pressure and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated. In conclusion, beneficial effects of antioxidants and folate were observed probably because the supplementation was used by young healthy subjects under carefully controlled conditions.
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PMID:Cardiovascular effects of oral Supplementation of vitamin C, E and folic acid in young healthy males. 1558 Aug 11

This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African-American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.
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PMID:Clinical trials update from the American Heart Association meeting: ACORN-CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A-HeFT, GEMINI, vitamin E meta-analysis, ESCAPE, CARP, and SCD-HeFT cost-effectiveness study. 1564 44

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.
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PMID:Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. 1564 79

Basic research suggests that oxidative stress may play an important role in many chronic diseases and provides plausible mechanisms by which natural antioxidants such as vitamin E may delay or prevent steps in atherogenesis. Dietary research has shown that those who consume higher amounts of fruits and vegetables have lower rates of heart disease and stroke, raising the possibility that antioxidants are protective. Results from large-scale human observational studies suggest that antioxidant consumption reduces the risk of developing cardiovascular disease (CVD). Both case-control and prospective cohort studies have carefully explored the relationship between vitamin E intake and plasma and tissue vitamin E levels and the risk of CVD. In many, but not all, of these studies vitamin E intake over an extended period was associated with decreased risk of cardiovascular events. Results from studies of blood levels are more limited and less consistent. This presentation summarizes data from the major observational studies. Overall, they support the possibility that vitamin E intake either from food or supplements may reduce risk of CVD; however, these studies have important limitations. For example, uncontrolled confounding can be similar in magnitude to the observed health effects, and antioxidant consumption may be merely a marker for a different cardioprotective factor (such as exercise or diet) that is responsible for these effects. In the search for small to moderate effects, randomized trials may be helpful, although to date, data from large-scale trials have been inconsistent. Several large-scale trials currently under way will help identify the potential benefits of vitamin E in the primary prevention of CVD and other chronic illness. Some are designed to test vitamin E alone as well as in combination with other antioxidant supplements because it is possible that antioxidants may be most effective if taken in particular combinations. Currently, the American Heart Association maintains that there are insufficient efficacy data from completed randomized trials to justify population-wide recommendations for use of vitamin E supplements in disease prevention.
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PMID:Vitamin E and cardiovascular disease: observational studies. 1575 54

The study of oxidative contributions to aging has reached sufficient maturity to support the development of interventional strategies designed to forestall or reverse protein cross-linking, oxidation of DNA and lipids, and mitochondrial senescence associated with chronic pathology and aging. Catalytic antioxidants, including combined superoxide dismutase (SOD) and catalase mimics, extend the lifespan of oxidatively compromised animals such as Mn-SOD knockout mice, and will be entering the clinic for radiation-induced dermatitis. Substituted phenacylthiozolium compounds that slow the formation and break extant protein cross-linkages formed via Maillard reactions, restoring vascular compliance in aged animals, and are showing efficacy in clinical trials. Non-feminizing estrogen analogs (eg, 17- alpha estradiol) block cytotoxicity in a host of oxidative stress models and moderate neuronal loss in MCAO stroke models. Efficacy of the polycyclic phenols is synergistically amplified by glutathione supplementation, suggesting that the two function as a redox couple analogous to vitamin E and ascorbate. Finally, discovery of novel small molecules designed to stabilize mitochondrial function during Ca(2+)-induced oxidative stress, such as that occurring during stroke or myocardial ischemia reperfusion, will be accelerated by a proprietary fluorescence resonance energy transfer assay developed at MitoKor. Maintaining mitochondrial function under these circumstances will improve cellular bioenergetic and oxidative status, and hence moderate secondary necrosis and apoptosis.
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PMID:Oxidative Stress and Aging - Second International Conference. Technologies for assessment and intervention strategies. 2-5 April 2001, Maui, USA. 1599 30

Motorcycle exhaust particles (MEP) are among the major air pollutants, especially in urban area of Taiwan. In our previous study, data showed that MEP induce proinflammatory and proallergic response profiles in BALB/c mice. Effects of MEP on interleukin (IL)-8 production in A549 human airway epithelial cells were further investigated in this study. It was found that MEP enhanced IL-8 protein and mRNA expression in human epithelial cells. Pretreatment with an NF-kappaB inhibitor (1 mM PDTC), extracellular signal-regulated kinase (ERK) inhibitor (50 microM PD98059), JNK inhibitor (25 microM SP600125), p38 inhibitor (2 microM SB203580), and three antioxidants (500 U/ml superoxide dismutase [SOD], 50 microM vitamin E, 10 mMN-acetylcysteine [NAC]) attenuated the MEP-induced increase in IL-8 production. Through further, direct detection of nuclear factor (NF)-kappaB activation in epithelial cells using immunoblotting of nuclear p65 and NF-kappaB reporter assay, data showed that MEP induced nuclear translocation of p65 and enhancement of NF-kappaB luciferase gene expression. MEP also induced activation of ERK, JNK, and p38 signaling pathways and produced an increase of oxidative stress in A549 cells. By using mitogen-activated protein kinase (MAPK) inhibitors and antioxidant, it was demonstrated that ERK inhibitor, JNK inhibitor, and antioxidants but not p38 inhibitor attenuated the MEP-induced increase in NF-kappaB reporter activity. In conclusion, evidence shows that filter-trapped particles emitted from unleaded gasoline-fueled, two-stroke motorcycle engines induce an increase in IL-8 production by activation of NF-kappaB in human airway epithelial cells.
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PMID:Motorcycle exhaust particles induce IL-8 production through NF-kappaB activation in human airway epithelial cells. 1607 65

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and beta-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.
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PMID:Micronutrients: dietary intake v. supplement use. 1631 97

The purpose of this paper is twofold: on the one hand, to confirm the positive results on n-3 PUFA from the overall results Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GlSSI)-Prevenzione trial; on the other, to summarize and describe how the results of an important trial can help generate hypotheses either on mechanisms of action or on differential results in particular subgroups of patients, as well as test the pathophysiological hypotheses that have accompanied in the years the story of the hypothesized mechanisms of action of a drug. GISSI-Prevenzione was conceived as a pragmatic population trial on patients with recent myocardial infarction and it was conducted in the framework of the Italian public health system. In GISSI-Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing the effectiveness of n-3 polyunsaturated fatty acids (PUFA) and vitamin E. Patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA at 1 g daily, but not vitamin E at 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall (-20%), cardiovascular (-30%), and sudden death (-45%). At variance from the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis", GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction.
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PMID:Antiarrhythmic mechanisms of n-3 PUFA and the results of the GISSI-Prevenzione trial. 1645 22


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