Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis involves structural change to the intima and media of medium- and large-sized arteries. Although an atherosclerotic plaque may remain clinically silent, it is prone to disruption, leading to local platelet activation and aggregation. Therefore, the major complication of atherosclerosis is thrombosis, with local occlusion or distal embolism - a generalized disease process known as atherothrombosis. The three main clinical manifestations of atherothrombosis are coronary heart disease (myocardial infarction and angina), peripheral arterial disease and cerebral ischaemia. Atherothrombosis is a leading cause of mortality, and stroke is the leading cause of disability in adults, the second most important cause of dementia and the third most common cause of death in Western countries. Ischaemic stroke accounts for 80% of strokes and atherothrombosis accounts for approximately 20% of all strokes. Criteria for atherothrombotic stroke are evidence of a 50% (or greater) stenosis of a cervical artery and exclusion of other potential causes. The incidence of cerebrovascular events is 2,900 per million inhabitants per year, consisting of 500 transient ischaemic attacks and 2,400 strokes, of which 75% are first-ever stroke. The prevalence of stroke in the same population is 12,000, of which 800 patients (7%) per year have recurrences. The risk of ipsilateral stroke is 5% per year and the risk of a cardiac event is higher at 7%. Besides optimal management of risk factors for atherothrombosis and carotid surgery, antiplatelet therapy is the cornerstone of vascular prevention. In secondary prevention, antiplatelet agents are effective in reducing the risk of further ischaemic events in patients with atherothrombosis. Clopidogrel, a newly licensed ADP receptor antagonist, is the only antiplatelet agent to have demonstrated its superiority versus aspirin for the reduction of major ischaemic events (myocardial infarction, ischaemic stroke, vascular death) in patients whose initial manifestation of atherothrombosis was one of the three main clinical manifestations of the disease (recent ischaemic stroke, myocardial infarction, established peripheral arterial disease).
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PMID:Atherothrombosis: a major health burden. 1131 15

A brief episode of ischemia renders the brain resistant against subsequent, longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. After global cerebral ischemia, ischemic tolerance may protect up to 90% of hippocampal CA1 neurons. In focal ischemia, this phenomenon reduces infarct volume by 20-60%. However, the basic molecular mechanisms of ischemic tolerance are largely unknown. During the induction phase, N-methyl-d-aspartate (NMDA) and adenosine receptors and, possibly, oxygen free radicals and conservation of energy metabolism are required. Protein kinases, transcription factors, and immediate early genes appear to transduce the signal into a tolerant response. Ischemic tolerance can be observed in different phases. The early phase lasts for several hours after the preconditioning stimulus and adenosine receptors and ATP-dependent potassium channels play a role similar to that in cardiac ischemic tolerance. The delayed protection, retained for a maximum of 2-4 days, currently is best explained by genetic remodeling with expression or repression of multiple genes. Several candidates have been identified to date, among them heat-shock proteins, cytokines, and antioxidant enzymes. Several studies have shown that angina pectoris before myocardial infarction represents a clinical correlate of experimental preconditioning protocols. Accordingly, evidence for a possible protective effect of transient ischemic attacks (TIAs) occurring before stroke are accumulating.
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PMID:[Ischemia tolerance; model for research, hope for clinical practice?]. 1132 Aug 60

Cerebral oxygenation (rSO(2)) in the region of sagittal sinus and main hemodynamic parameters were measured in 112 patients with ischemic heart disease and class II-III angina. Four groups of patients were distinguished according to degree of rSO(2) lowering. Hemodynamics and oxygen transport function of the blood were proportionally related to degree of rSO(2) lowering. Normal rSO(2) (>70%) and degree lower (70-61%) was associated with predicted (desirable) cerebral blood flow. Lower rSO(2) values (60-50%) were accompanied with increased oxygen utilization (by 20-25%). Critical rSO(2) lowering (below 50%) was associated with>/=75% rise of oxygen utilization what was indicative of decreased brain blood flow and cerebral ischemia.
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PMID:[The study of cerebral oxygenation and central hemodynamics in patients with ischemic heart disease at rest and during physical effort.]. 1547 72

Elevated serum uric acid (UA) is frequently encountered in individuals with hypertension, but whether the relationship between UA and cardiovascular events is circumstantial or causal remains to be answered. We examined the association between serum UA and left ventricular mass index (LVMI) and investigated prospectively whether the combination of UA and LVMI can predict the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 619 subjects (mean age, 61 years; 52% female) free of prior CVD were included in this study. A significant association between UA and LVMI was also confirmed in multiple regression analysis (male: F=4.29, P<0.04; female: F=4.24, P<0.05). During follow-up (mean, 34 months), 28 subjects (14 female) developed CVD including myocardial infarction, angina pectoris, congestive heart failure, cerebral infarction, and transient cerebral ischemia. Sex-specific median values were used to separate the higher group from the lower group of UA and LVMI. Kaplan-Meier curves showed a significantly poorer survival rate in the group with higher UA and LVMI (LVMI, male: >126.9, female: >112.0 g/m2; UA, male: >374.7, female: >303.3 micromol/L; log-rank chi2=13.18; P<0.01). Multivariate Cox regression analysis showed that the combination of higher UA and LVMI was an independent predictor for CVD events (hazard ratio, 2.38; P<0.03). Our findings demonstrate that UA is independently associated with LVMI and suggest that the combination of hyperuricemia combined with left ventricular hypertrophy is an independent and powerful predictor for CVD. The association between UA and CVD events may be introduced in part because of a direct association of UA with LVMI.
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PMID:Uric acid, left ventricular mass index, and risk of cardiovascular disease in essential hypertension. 1638 May 20

Acute hypertensive emergencies occur in 5 to 35 % of the patients in perioperative care. This is associated with an increase in perioperative complications: the rate of bleedings, myocardial infarctions, cerebral ischemia and overall mortality is increased 4-fold. Before an operation, it is of utmost importance to recognize predictors for hypertensive emergencies and to achieve an adequate blood pressure control. There has so far been no agreement on a blood pressure threshold at which blood pressure needs to be reduced. Antihypertensive therapy is a bedside decision of the responsible physician. It aims at a rapid decrease of hypertensive peaks without risking a reduced organ perfusion. The optimal drug for the treating hypertensive emergencies should have a rapid and safe action. Antihypertensives of first choice are esmolol, metoprolol, urapidil or clonidin. The oral therapy with nifedipine or nitrendipine has the risk of abrupt hypotensive episodes and should therefore only be administered after exclusion of an acute coronary syndrome or cardiac failure Because of its toxicity sodium nitroprusside is an antihypertensive drug of second choice. Nitrates or diuretics are supplementary drugs for patients with angina pectoris, cardiac failure or renal insufficiency. Newer substances (fenoldopam, nicardipine, clevidipine) have promising kinetic properties but are not as yet been approved for antihypertensive treatment in Germany.
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PMID:[Treatment of peri- and postoperative hypertensive emergencies]. 1931 72

Migraine, especially migraine with aura (MA), is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication, and cardiovascular mortality. The mechanisms which link migraine to ischemic vascular disease remain uncertain and are likely to be complex. Cortical spreading depression, the presumed substrate of aura, may directly predispose to brain lesions and that would explain why MA is consistently demonstrated as a risk factor for cerebral ischemia, while for migraine without aura (MO), the evidence is less consistent. Additionally, individuals with migraine have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD), including hypertension, diabetes, and hyperlipidemia. The increased prevalence of CVD risk factors is also higher for MA than for MO. Since the evidence linking migraine and CVD is getting robust, neurologists should be aware of this association. Individuals with MO seem to be at little increased risk of CVD. MA is associated with an increased risk of ischemic stroke and likely also for other ischemic CVD events. Accordingly, heightened vigilance is recommended for modifiable cardiovascular risk factors in migraineurs, especially with MA. Ultimately, it will be important to determine whether MA is a modifiable risk factor for CVD and if preventive medications for migraine or antiplatelet therapy might reduce the risk of CVD in patients with MA.
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PMID:Migraine and cardiovascular disease: possible mechanisms of interaction. 1947 Sep 70

Calcium channel blockers (CCBs), which alter the intracellular calcium concentration by modifying calcium flux across cell membranes and affect various intracellular signaling processes, have been long and widely used to treat essential hypertension and certain types of cardiac diseases such as angina pectoris. Among five subtypes of calcium channels, only specific agents for L-type calcium channels have been used as therapeutics. Animal experiments have indicated that topical application of CCBs, especially verapamil, caused significant intraocular pressure (IOP) reductions, while ocular hypotensive effects in humans were not substantial. Although the results obtained for nifedipine and nimodipine were not always consistent, CCBs generally dilate isolated ocular vessels and increase ocular blood flow in experimental animals, normal humans, and patients with open-angle glaucoma (OAG). Several single-centered, hospital-based, prospective studies have suggested that nimodipine, brovincamine, and nilvadipine had beneficial effects on visual function not only in normal humans but also in patients with OAG, while the results of population-based and case-controlled studies were not always consistent with those obtained in hospital-based studies. In vitro studies showed that CCBs exerted neuroprotective effects on neurons undergoing apoptosis and necrosis. Although the neuroprotective effects of CCBs have been well documented in experimental cerebral ischemia models, no controlled studies have shown the clinical efficacy of CCBs in stroke or cerebral ischemia. Neuroprotective effects also were documented in retinal ganglion cells and photoreceptors in experimental animals. Some ophthalmic beta-adrenoceptor antagonists, especially betaxolol, interact with L-type calcium channels and show calcium channel-blocking activity, which may be partly responsible for the neuroprotective effects of these drugs reported in experimental animals. Based on the reported findings of CCBs and that the results of clinical studies in acute cerebral ischemia may not be directly applicable to a chronic neurodegenerative ocular disorder, such as OAG, CCBs deserve future study to investigate strategies that are additive or synergetic to ocular hypotensive therapy for OAG, especially in patients with lower IOP.
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PMID:Use of calcium channel blockers for glaucoma. 2093 4

Dyslipidemia is a common finding in patients with thyroid disease, explained by the adverse effects of thyroid hormones in almost all steps of lipid metabolism. Not only overt but also subclinical hypo- and hyperthyroidism, through different mechanisms, are associated with lipid alterations, mainly concerning total and LDL cholesterol and less often HDL cholesterol, triglycerides, lipoprotein (a), apolipoprotein A1, and apolipoprotein B. In addition to quantitative, qualitative alterations of lipids have been also reported, including atherogenic and oxidized LDL and HDL particles. In thyroid disease, dyslipidemia coexists with various metabolic abnormalities and induce insulin resistance and oxidative stress via a vice-vicious cycle. The above associations in combination with the thyroid hormone induced hemodynamic alterations, might explain the increased risk of coronary artery disease, cerebral ischemia risk, and angina pectoris in older, and possibly ischemic stroke in younger patients with overt or subclinical hyperthyroidism.
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PMID:Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. 2178 82

Rho-associated coiled-coil forming protein kinases (ROCKs), the downstream target proteins of RhoA, are ubiquitously expressed serine-threonine protein kinases. ROCKs have diverse cellular functions, e.g. smooth muscle contraction, actin cytoskeleton organization, cell adhesion, and gene expression. Accumulating evidence has revealed that ROCKs are substantially involved in cardiovascular disorders such as angina, cerebral ischemia, myocardial ischemia, and cardiac hypertrophy. So far, the significant relationship of ROCKs with endothelial function has been reported. ROCKs inhibition by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase, resulting in the reduction of vascular inflammation and atherosclerosis. Meanwhile, it has been also demonstrated that endogenous nitric oxide could inhibit RhoA/ROCK signaling pathway. Taken together, there might be critical crosstalk of ROCKs with endothelial function. In addition, we further focus on leukocyte ROCK activity as a surrogate marker in patients with atherosclerosis-related diseases. Indeed, leukocyte ROCK activity has been shown to be increased in atherosclerotic patients, indicating the possible usage of leukocyte ROCK activity as a surrogate marker similar to endothelial function evaluated by flow-mediated dilation. Here, we review concerning ROCK signaling pathway, especially focusing on the crosstalk of ROCKs with endothelial function.
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PMID:Striking crosstalk of ROCK signaling with endothelial function. 2260 93

Cardiovascular diseases constitute the largest of death in developed countries, being atherosclerosis the major contributor. Atherosclerosis is a process of chronic inflammation, characterized by the accumulation of lipids, cells, and fibrous elements in medium and large arteries. There is a continuum in atherosclerotic cardiovascular pathology that extends from the initial endothelial damage to diseases such as angina, myocardial infarction, and stroke. The extent of inflammation, proteolysis, calcification, and neovascularization influences the development of advanced lesions (atheroma plaques) on the arteries. Plaque rupture and the ensuing thrombosis cause the acute complications of atherosclerosis, i.e., myocardial infarction and cerebral ischemia. Thus, identification of early biomarkers of plaque unstability and susceptibility to rupture is of capital importance in preventing acute events. In recent years proteomics has been successfully applied to study proteins involved in these pathological processes. Thus, proteomic studies have been carried out focusing on different elements such as vascular tissues (arteries), artery layers, cells looking at proteomes and secretomes, plasma/serum, exosomes, lipoproteins, and metabolites. This chapter will provide an overview of latest advances in proteomic studies of atherosclerosis and related vascular diseases.
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PMID:Vascular proteomics. 2358 80


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