Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic nonvalvular atrial fibrillation is associated with an overall risk of thromboembolic complications of 4.5% per year. Advancing age, prior stroke or transient cerebral ischaemia, diabetes, hypertension, and impaired function of the left ventricle are known risk factors. Placebo-controlled trials have demonstrated that oral anticoagulant therapy with warfarin is effective for primary and secondary prevention of ischaemic stroke, reducing the risk by 68%. The effect of aspirin is still controversial, reducing the risk by 18-44%. Recent clinical trials have investigated the effect of warfarin given at a very low intensity alone or combined with aspirin. The results from the SPAF III study demonstrated that a combination of mini-intensity warfarin plus aspirin was insufficient for stroke prevention in atrial fibrillation. More trials have now confirmed that oral anticoagulation at INR-values below 2.0 is not effective for prevention of thromboembolic events in these patients. It is currently recommended that patients at a high risk of stroke are treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65 years without other risk factors can be given aspirin 325 mg day-1.
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PMID:Oral anticoagulation in nonvalvular atrial fibrillation. 1035

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
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PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

BACKGROUND: We investigated the association of cigarette smoking with high-grade carotid artery stenosis in patients with ischemic stroke and transient ischemic attacks. METHODS: Prospectively collected data from 404 patients with focal brain ischemia were used for a cross-sectional study estimating the association between cigarette smoking and high-grade carotid artery stenosis (diagnosed by Doppler-ultrasound and defined as a luminal narrowing of > or = 70%). Cerebral ischemia patients with normal sonographic findings served as a comparison group. Multivariate logistic regression models were used for statistical tests to determine the association between smoking and high-grade carotid stenosis. Age, gender, hypertension, diabetes mellitus, hypercholesterolemia and co-existing heart disease (myocardial infarction, angina, heart failure) were considered potential confounders. RESULTS: High-grade carotid stenoses were found in 25% (n = 101) of the patients; 39% (n = 156) were classified as smokers. Smoking (odds ratio 3.6, 95% confidence interval [CI] 2.2 to 5.8), hypercholesterolemia (odds ratio 1.8; CI 1.1 to 2.8) and preexisting heart disease (odds ratio 1.7; CI 1.1 to 2.7) were significantly associated with carotid stenosis > or = 70%. The impact of smoking augmented with increasing degree of stenosis (odds ratio for stenoses > or = 80%: 4.3, CI 2.3 to 7.7), whereas the association with hypercholesterolemia, and co-existing heart disease decreased in strength for stenoses greater than 80%. Hypertension and diabetes mellitus were not found to be significantly with high-grade carotid artery stenoses. CONCLUSION: Smoking is an independent determinant of severe carotid artery stenosis in patients with focal cerebral ischemia.
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PMID:[In Process Citation] 1059 30

The Alzheimer type of dementia and stroke are known to increase at comparable rates with age. Recent advances suggest that vascular risk factors linked to cerebrovascular disease and stroke in the elderly significantly increase the risk of developing Alzheimer's disease (AD). These include atherosclerosis, atrial fibrillation, coronary artery disease, hypertension, and diabetes mellitus. Moreover, review of various autopsy series shows that 60-90% of AD cases exhibit variable cerebrovascular pathology. Although some vascular lesions such as cerebral amyloid angiopathy, endothelial degeneration, and periventricular white matter lesions are evident in most cases of AD, a third will exhibit cerebral infarction. Despite the interpretation of pathological evidence, longitudinal clinical studies suggest that the co-existence of stroke and AD occurs more than by chance alone. Strokes known to occur in patients with Alzheimer syndrome and most frequently in the oldest old substantially worsen cognitive decline and outcome, implicating some interaction between the disorders. Nevertheless, the nature of a true relationship between the two disorders seems little explored. What predisposes to strokes in underlying cognitive decline or AD? Is it possible that cerebral ischemia is a causal factor for AD? I examined several vascular factors and the vascular pathophysiology implicated in stroke and AD, and propose that cerebral ischemia or oligemia may promote Alzheimer type of changes in the aging brain. Irrespective of the ultimate pathogenetic mechanism, these approaches implicate that management of peripheral vascular disease is important in the treatment or prevention of Alzheimer's disease or mixed dementia.
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PMID:The role of cerebral ischemia in Alzheimer's disease. 1086 17

Diabetes is associated with increased neural damage after transient cerebral ischemia. Recently, leukocytes, which are thought to play a central role in ischemia-reperfusion injury, have been suggested to be involved in exacerbated damage after transient ischemia in diabetic animals. The present study was designed to clarify whether the anticipated worse outcome after transient cerebral ischemia in diabetic animals was due to augmented leukocyte-mediated neural injury. Using rats with streptozotocin-induced diabetes of 4-wk duration, we investigated leukocyte-endothelial cell interactions during reperfusion after a transient 60-min period of retinal ischemia. Unexpectedly, postischemic diabetic retina showed no active leukocyte-endothelial cell interactions during reperfusion. The maximal numbers of rolling and accumulating leukocytes in diabetic retina were reduced by 73.6 and 41.2%, respectively, compared with those in nondiabetic rats. In addition, neither preischemic insulin treatment of diabetic rats nor preischemic glucose infusion of nondiabetic rats significantly influenced leukocyte-endothelial cell interactions during reperfusion. The present study demonstrated that high blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. Furthermore, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.
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PMID:Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia. 1095 57

GPI 6150 (1,11b-dihydro-[2H]benzopyrano[4,3,2-de]isoquinolin-3-one) is a novel inhibitor of poly(ADP-ribose) polymerase (PARP). It has demonstrated efficacy in rodent models of focal cerebral ischemia, traumatic brain injury, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine damage to dopaminergic neurons, regional myocardial ischemia, streptozotocin-induced diabetes, septic shock, and arthritis. Here we report the structure of GPI 6150, its enzymatic characteristics, and biochemical property in cytoprotection. As a competitive PARP inhibitor (K(i) = 60 nM), GPI 6150 protected the P388D1 cells against hydrogen peroxide cytotoxicity, by preventing PARP activation and the depletion of NAD(+), the substrate for PARP. To address the concerns of potential side effects of PARP inhibition, we tested GPI 6150 and found it had no effect on the repair and expression of a plasmid DNA damaged by N-methyl-N'-nitro-N-nitrosoguanidine. Neither did it affect dehydrogenases with NAD co-enzyme. GPI 6150 was much less potent to inhibit mono-ADP-ribosyltransferase. There was no selectivity for GPI 6150 between PARP isozymes. These attributes render GPI 6150 a useful tool to probe the functions of PARP.
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PMID:GPI 6150 prevents H(2)O(2) cytotoxicity by inhibiting poly(ADP-ribose) polymerase. 1109 54

Diabetic hyperglycemia increases brain damage after cerebral ischemia in animals and humans, although the underlying mechanisms remain unclear. Gender-linked differences in ischemic tolerance have been described but have not been studied in the context of diabetes. In the current study, we used a model of unilateral common carotid artery ligation, combined with systemic hypoxia, to study the effects of diabetes and gender on hypoxic-ischemic (HI) brain damage in the genetic model of Type II diabetes, the db/db, mouse. Male and female, control and db/db, mice were subjected to right common carotid artery ligation followed by varying periods of hypoxia (8% oxygen/92% nitrogen) to assess mortality, infarct volume, and tissue damage by light microscopic techniques. End-ischemic regional cerebral blood flow (CBF) was determined using [14C] iodoantipyrine autoradiography. Glycolytic and high energy phosphate compounds were measured in blood and brain by enzymatic and fluorometric techniques. Gender and diabetes had significant effects on mortality from HI and extent of brain damage in the survivors. Female mice were more resistant than their male counterparts, such that the severity (mortality and infarction size) in the male diabetics > female diabetics - male controls > female controls. Endischemic CBF and depletion of cerebral high energy reserves were comparable among all groups. Surprisingly, female diabetic mice were more hyperglycemic and demonstrated a greater prolonged lactacidosis than the males; however, they were more resistant to damage. The results suggest a unique pathophysiology of hypoxia-ischemia in the female diabetic brain.
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PMID:Experimental stroke in the female diabetic, db/db, mouse. 1114 68

Initially it was considered that moxonidine, like clonidine, acted at central (2)-adrenoceptors to reduce blood pressure. With the characterisation of imidazoline binding sites distinct from (2)-adrenoceptors, the consensus became that moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release and this may contribute to its ability to lower blood pressure. The predominant site of action of moxonidine may also depend on route of administration, with imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors predominant after systemic administration. The controversy over the mechanism and site of action with moxonidine is ongoing. In animal models, moxonidine lowers blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has beneficial effects in animal models of diabetes and kidney disease. Moxonidine increases sodium and water excretion in rats, but not humans. Animal studies indicate that moxonidine may be useful in the treatment of glaucoma by reducing intra-ocular pressure. Animal studies show that moxonidine may also be effective in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine are of the one-compartment model with first-order absorption. Renal elimination is the major route of elimination and individual titration of moxonidine is needed in patients with renal impairment. There is overwhelming evidence that moxonidine is a safe and effective antihypertensive. A large clinical trial of moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in the moxonidine group. Moxonidine should not be used in patients with heart failure, but there are no obvious reasons to stop its use as an antihypertensive, or its development for other clinical uses.
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PMID:Moxonidine: some controversy. 1133 90

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.
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PMID:[Morphologic and clinical sequelae of focal ischemic lesions]. 1137 5

Chronic infection may increase the risk for ischemic stroke. Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke. We analyzed IgG antibodies against H. pylori in 109 patients with acute cerebral ischemia and 82 age- and sex-matched control patients with non-vascular and non-inflammatory neurological diseases. Antibody titers were significantly higher in patients than in control subjects (p=0.007). H. pylori seropositivity tended to be more common in patients (odds ratio (OR) 1.55, 95% confidence interval (ci) 0.87-2.76), but this trend was further attenuated in multivariate analysis (OR 1.42; 95% 0.75-2.67) with hypertension, diabetes mellitus, current or previous smoking, previous cerebral ischemia and low socioeconomic status. H. pylori seropositivity increased the odds for cerebral ischemia of atherothrombotic origin in univariate (OR 3.63; 95% ci 1.37-9.65) and multivariate analysis (OR 3.53; 95% ci 1.09-11.4). H. pylori seropositivity may be an independent risk factor for stroke of atherothrombotic origin.
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PMID:Helicobacter pylori infection as an independent risk factor for cerebral ischemia of atherothrombotic origin. 1141 64


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