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

As the average age in many countries steadily rises, heart infarction, stroke, and cancer become the most common causes of death in the 21st century. The causes of these disorders are many and varied and include genetic predisposition and environmental influences, but they all share a common feature in that limitation of oxygen availability participates in the development of these pathological conditions. However, cells and organisms are able to trigger an adaptive response to hypoxic conditions that is aimed to help them to cope with these threatening conditions. This review provides a description of several systems able to sense oxygen concentration and of the responses they initiate both in the acute and also in long-term hypoxia adaptation. The role of hypoxia in three pathological conditions, myocardial and cerebral ischemia as well as tumorigenesis, is briefly discussed.
 ...
PMID:Physiological and pathological responses to hypoxia. 1516 23

Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is a potent cholesterol-lowering drug that reduces the risk of myocardial infarction and stoke. In this study, we examined its neuroprotective effects against hippocampal CA1 neuronal damage following transient cerebral ischemia in gerbils. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries for 5 min. Pitavastatin, at a dose of 3, 10 or 30 mg/kg, was administered orally twice a day for 5 consecutive days and transient cerebral ischemia was induced in mice 1 h after the last treatment with pitavastatin. Histopathological observations showed that neuronal damage to the hippocampal CA1 neurons, which was observed 5 days after ischemia in animals, was prevented by pitavastatin treatment. Immunohistochemical staining for copper/zinc superoxide dismutase (SOD) and manganese SOD decreased in the hippocampal CA1 sector of gerbils 2 days after ischemia when histological neuronal destruction was not yet found, but was clearly observed in pitavastatin-treated animals. These results indicate that pitavastatin can protect dose-dependently against ischemia-induced neuronal damage and that the mechanism of the neuroprotection may be related to the preservation of SODs, especially copper/zinc-SOD. This in part explains how pitavastatin therapy, which targets free radicals, has beneficial effects against disorders including ischemic stroke.
 ...
PMID:Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, reduces hippocampal damage after transient cerebral ischemia in gerbils. 1533 28

Carotid endarterectomy is one of the most common vascular and neurosurgical operations. Controversies regarding its indications and safety have required several decades before general resolution, while its methodology is still debated. The first operations are described with particular emphasis on the epic successful procedure in 1954 by Eastcott and Rob. Early procedures were on patients with frank strokes with poor results. The development of carotid endarterectomy was slow because neurologists were unsure of its effectiveness and safety as the mortality and stroke results recorded by untrained surgeons were unacceptable. It was not until some 35 years after its introduction that randomised controlled trials, both in North America and Europe, defined its indications and demonstrated its benefits for both symptomatic and asymptomatic carotid stenosis. Clamping of the carotid vessels, required during endarterectomy, may result in various degrees of cerebral ischaemia. Methods to determine which patients need shunting are compared. The author has employed local neck block anesthesia since 1972, which is the only method that provides constant neurological assessment for selective shunting during carotid cross clamping. Evidence is presented showing that local anaesthesia also reduces complications of general anaesthesia, especially myocardial infarction. The technique of neck block, conventional endarterectomy and two varieties of eversion endarterectomy for carotid disease are described. Each of these techniques of endarterectomy is advantageous in certain circumstances, suggesting that vascular surgeons should ideally be proficient in each. Likewise, the management of early stroke after operation, stenotic or occluded external carotid the presence of retinal Hollenhorst plaques, and the totally occluded internal carotid, is presented. Finally, observations on some famous figures who suffered from cerebrovascular complications secondary to carotid disease and what effect it may have had on world history is discussed.
 ...
PMID:The evolution of extracranial carotid artery surgery as seen by one surgeon over the past 40 years. 1557 Jul 74

Normal tissue function depends on adequate supply of oxygen through blood vessels. Reduced oxygen supply (hypoxia) induces a variety of specific adaptation mechanisms in mammals that occur at the cellular, local and systemic level. These mechanisms are in part governed by the activation of the hypoxia-inducible transcription factors HIF-1 and HIF-2. Prolyl and asparaginyl hydroxylases as recently characterized oxygen sensors allow the regulation of HIFs that in turn modulate expression of hypoxically regulated genes such as VEGF. VEGF plays a key role in the formation of a functional and integrated vascular network required during physiological processes such as embryogenesis or female reproductive cycle as well as during a variety of pathological processes such tumor growth, wound healing, retinopathy and ischemic diseases (myocardial infarction, cerebral ischemia). However, other angiogenic factors, such as angiopoietins, PDGF, ephrins and erythropoietin are additionally needed to enable the formation of a functional vascular network. Many of these factors are activated during hypoxia although no HIF binding sites have yet been identified in the regulatory sequences of theses genes. Hypoxia-induced gene products that result in new vessel growth may be part of a self-regulated physiological protection mechanism preventing cell injury, especially under conditions of chronically reduced blood blow (chronic ischemia).
 ...
PMID:Angiogenesis--a self-adapting principle in hypoxia. 1561 78

Discovery that the hormone erythropoietin (EPO) and its receptor play a significant biological role in tissues outside of the hematopoietic system has fueled significant interest in EPO as a novel cytoprotective agent in both neuronal and vascular systems. Erythropoietin is now considered to have applicability in a variety of disorders that include cerebral ischemia, myocardial infarction, and chronic congestive heart failure. Erythropoietin modulates a broad array of cellular processes that include progenitor stem cell development, cellular integrity, and angiogenesis. As a result, cellular protection by EPO is robust and EPO inhibits the apoptotic mechanisms of injury, including the preservation of cellular membrane asymmetry to prevent inflammation. As the investigation into clinical applications for EPO that maximize efficacy and minimize toxicity progresses, a deeper appreciation for the novel roles that EPO plays in the brain and heart and throughout the entire body should be acquired.
 ...
PMID:New avenues of exploration for erythropoietin. 1584 Aug 58

Adrenomedullin (AM) has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of delayed AM gene transfer in cerebral ischemia. Three days after a 1-hr occlusion of the middle cerebral artery (MCAO), rats were injected intravenously with adenovirus harboring human AM cDNA. The experiment was terminated 7 days after MCAO. AM gene transfer significantly reduced cerebral infarct size compared with that of rats before virus injection and compared with that of rats injected with control virus. The expression of recombinant human AM was identified in ischemic brain by immunostaining. Morphological analyses showed that AM gene transfer enhanced the survival and migration of astrocytes into the ischemic core. Cerebral ischemia markedly increased astrocyte apoptosis, and AM gene delivery significantly reduced apoptosis to near normal levels as seen in sham control rats. Similarly, in primary cultured astrocytes, AM stimulated cell migration and inhibited hypoxia/reoxygenation-induced apoptosis. The effects of AM on both migration and apoptosis were abolished by calcitonin gene-related peptide [CGRP(8-37)], an AM receptor antagonist. Enhanced cell survival after AM gene transfer was accompanied by markedly increased cerebral nitric oxide and Bcl-2 levels, as well as Akt and GSK-3beta phosphorylation, but reduced NADPH oxidase activity and superoxide production. Inactivation of GSK-3beta by phosphorylation led to reduced GSK-3beta activity and caspase- 3 activation. These results indicate that exogenous AM provides neuroprotection against cerebral ischemia injury by enhancing astrocyte survival and migration and inhibiting apoptosis through suppression of oxidative stress-mediated signaling events.
 ...
PMID:Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival. 1568

Lung transplantation is currently the most effective means of improving survival and quality of life in patients with end-stage cystic fibrosis. In reviewing our 6-year experience we sought to evaluate complications and survival after sequential bilateral lung transplantation. Between October 1996 and October 2002, 114 patients with cystic fibrosis were referred to us from 15 Italian regional centers and 2 support centers for cystic fibrosis as possible candidates for lung transplantation. Of these 114 patients, 99 were included in the waiting list and 15 were refused. The mean time spent on the waiting list was 6.8+/-5.2 months (range 1 day-21 months) for those patients receiving lung transplantation, and 5.4+/-4.5 months (range 10 days-18 months) for those 35 patients who died while on the waiting list. A total 55 patients (6 children and 49 adults), mean age 25.6+/-6.6 years (range 9-52 years), 29 males, underwent bilateral sequential lung transplantation. One patient had a second transplantation 14 months after the first. The most frequent medical non-infective complications after transplantation were chronic renal failure (n=27 patients), diabetes (n=31), osteoporosis (n=17), arterial hypertension (n=14), seizures (n=4), transient cerebral ischaemia (n=1), and transient bilateral blindness (n=1). Bacterial lower airways respiratory infections with the organisms that colonized patients' airways before lung transplantation developed in 42 patients; cytomegalovirus (CMV) infection in 41; and opportunistic infections of the lung with Pneumocystis carinii in 3 patients. Cultures of sputum or bronchoalveolar lavage fluid grew Aspergillus fumigatus in nine patients; aspergillosis of right bronchial anastomosis developed in one patient and a lung infection in another. Another patient had a pulmonary infection secondary to Aspergillus niger. An average of 1.3 episodes of acute rejection developed per patient in the first 6 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome was 95% at 1 year, 82.5% at 2 years, 70% at 3 years, and 65% at 4, 5 and 6 years. Actuarial survival rates were 80% at 1 month, 79% at 1 year, 74% at 2 years, 70% at 3 years and 58% at 4, 5 and 6 years. Ten patients (17.8%) died in the early postoperative period (1-30 days) for the following reasons: primary graft failure (n=4), multiorgan failure (n=3), Burkholderia cepacia sepsis (n=1), myocardial infarction (n=1), and pulmonary embolism (n=1). Mortality was accounted for by 9 patients (16%) who died from 9 to 43 months after lung transplantation, for the following reasons: P. carinii infection (n=2), bronchiolitis obliterans syndrome (n=4), A. fumigatus pulmonary infection (n=1), unknown cause (n=1) and suicide (n=1). In conclusion, the leading causes of morbidity after lung transplantation for cystic fibrosis are pulmonary bacterial infection and opportunistic infections. Bronchiolitis obliterans develops in more than half of lung transplant recipients who survive for more than 3 years and is an important cause of death in the late post transplantation period.
 ...
PMID:Lung transplantation for cystic fibrosis: 6-year follow-up. 1591 93

Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and BB) and B- (AA) genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The frequency of soft plaques increased in B+ in comparison to B- patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2 polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid plaque rupture and cerebral ischaemia.
 ...
PMID:1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. 1599 11

Case-control studies and a few prospective studies have indicated that chronic infections may add to the risk of stroke and that acute infections may act as trigger factors for stroke. Such chronic infections include periodontal disease, infection with Chlamydia pneumoniae or Helicobacter pylori, and chronic bronchitis. A causal role of these infectious diseases has not been proved, given conflicting study results, possible residual confounding in observational studies, and the lack of evidence from interventional trials. Therefore, special treatment regimens for stroke prevention based on serologic or genomic evidence of infection are not indicated outside of randomized studies at present. However, the preliminary available evidence suggests that in patients with previous cerebral ischemia, clinically diagnosed chronic infections should be taken seriously and should receive the treatment that is indicated according to current guidelines. This may include appropriate treatment of moderate or severe periodontitis and of chronic bronchitis. Inflammatory parameters (eg, C-reactive protein, leukocyte count, fibrinogen) are independently associated with the risk of first or recurrent stroke. The question of whether these indexes are causally related to stroke or merely represent risk markers is not sufficiently clarified. Their use in monitoring individual risk in daily clinical practice is limited at present by the lack of clearly defined therapeutic strategies to modify these parameters, although statins and other drugs can influence inflammatory markers. Observational studies have shown that influenza vaccination is significantly and independently associated with a reduced risk of stroke and myocardial infarction. Although interventional studies in stroke are lacking, it is recommendable that in accordance with current guidelines patients with previous vascular disease, including stroke, patients with high risk of stroke, and all subjects above age 60, receive an influenza vaccination annually.
 ...
PMID:Role of anti-infective strategies in the prevention of stroke. 1600 50

rHuEPO (recombinant human erythropoietin) is a haemopoietic growth factor and a primary regulator of erythropoiesis that is used for the treatment of chronic anaemia associated with RA (rheumatoid arthritis). Erythropoietin also appears to modulate a broad array of cellular processes, including progenitor stem-cell development, cellular integrity, angiogenesis and oxidative damage. These diverse activities suggest the exciting possibility of multiple roles for rHuEPO therapy in a variety of disorders other than RA, including cerebral ischaemia, myocardial infarction, chronic congestive heart failure and cancer. Thus it appears that rHuEPO may be a pleiotropic agent, capable of influencing tissue remodelling independently of its established erythropoietic role. Whereas these effects may be largely beneficial, dose-related side effects could have implications for the safe therapeutic use of rHuEPO and its illegal use as a performance-enhancing agent in endurance sports.
 ...
PMID:Novel tissue remodelling roles for human recombinant erythropoietin. 1624 63


<< Previous 1 2 3 4 5 6 7 8 9 10