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)

The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse; spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS), electrically-based (MES seizures in mice and rats, corneally-kindled seizures in rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic acid, quinolinic acid and strychnine). When compared to valproate, orally administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and showed a safety index one to three-fold greater. Following a timed intravenous administration of PTZ to mice, MDL 27,192, but not phenytoin or carbamazepine, consistently increased the latencies to first twitch and clonus. MDL 27,192 was active in a genetic model of absence epilepsy, the GAERS rat model. These data indicate that MDL 27,192 likely exerts its anticonvulsant action by affecting seizure spread and by raising seizure threshold. MDL 27,192 did not display any signs of tolerance following subchronic (15 day) administration. In tests of neuroprotective potential, MDL 27,192 reduced infarct volume in a permanent middle cerebral artery occlusion model of focal cerebral ischemia in rats and reduced the loss of hippocampal dentate hilar neurons in an animal model of unilateral head injury. In summary, MDL 27,192 possesses a broad-spectrum anticonvulsant profile. The potential for reduced tolerance and neuroprotective activity are additional positive features of MDL 27,192's preclinical profile.
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PMID:Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties. 916 90

Polyvalent intravenous immunoglobulin (IVIg) is considered to be standard therapy for a variety of autoimmune and idiopathic disorders. Several reports have emphasized the temporal association between administration of IVIg and thrombotic events. Recent experience with a patient who suffered a large myocardial infarction shortly after receiving IVIg led the authors to review the clinical and basic literature on administration of IVIg as a possible precipitant for myocardial infarction. Although the existence of an association between IVIg administration and myocardial ischemia has not been demonstrated in clinical trials, a body of clinical experience has begun to accumulate that is suggestive of an association between IVIg administration and cardiac and cerebral ischemia in older individuals or individuals with a known history of ischemic disease. Basic research demonstrating that IVIg administration may increase blood viscosity suggests that such an association is plausible.
Can J Cardiol 1997 Aug
PMID:Intravenous immunoglobulin, blood viscosity and myocardial infarction. 928 45

To evaluate the additional value of transesophageal (TEE) compared with transthoracic (TTE) echocardiography and the role of patent foramen ovale (PFO) and deep vein thrombosis in the work-up of embolic events, patients with presumed cardiac embolic stroke or transient ischemic attack (neurovascular etiology was excluded) were prospectively studied by transthoracic and transesophageal contrast echocardiography. If PFO was detected echocardiographically, PFO size was assessed semiquantitatively and phlebography of both legs was performed. Two hundred forty-two consecutive patients (153 men, 60 +/- 15 years) were studied. In 197 patients, neuroimaging showed evidence of embolic infarction. TEE identified 138 potential cardiac sources of embolism in 111 patients, compared with 69 by TTE (p <0.01) in 59 patients. TEE detected potential cardiac sources in 52 patients with negative TTE examination and was significantly superior compared with TTE for identifying left atrial thrombi, spontaneous echo contrast, PFO, atrial septal aneurysm, and atheroma of the ascending aorta. In patients with a positive TTE, additional diagnostic information by TEE was found in only 6 patients and did not change therapy. Phlebography was performed in 53 patients with PFO and revealed deep vein thrombosis in 5 patients (9.5%); all had medium or large PFOs. Thus, in patients with cerebral ischemia of suspected cardiogenic origin and a normal TTE examination, TEE detects potential causes of embolism in 31% of patients and is therefore of diagnostic relevance. Conversely, in the presence of a diagnostic TTE an additional TEE confers only marginal diagnostic benefit. Deep venous thrombosis was detected in nearly 10% of patients with PFO as the sole identifiable cardiac risk factor. Given that in 4 of 5 patients deep vein thrombosis was clinically silent, phlebography should be performed in patients with medium or large interatrial shunts if paradoxical embolism is suspected.
Am J Cardiol 1997 Oct 15
PMID:Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. 935 79

In the general population, peripheral atherosclerosis is a strong predictor of cardiovascular disease and death. In patients with known coronary artery disease, it is unclear whether the presence of additional noncoronary atherosclerosis is of further prognostic value. In the Bypass Angioplasty Revascularization Investigation, 5-year outcome was compared between patients with and without clinically evident noncoronary atherosclerosis. Within the subgroup with noncoronary atherosclerosis, surgery, and angioplasty treatment strategies were compared. Noncoronary atherosclerosis was defined as claudication, peripheral vascular surgery, abdominal aortic aneurysm, history of cerebral ischemia, or carotid disease. Among 1,816 patients, 303 (17%) had noncoronary atherosclerosis. These patients were more likely to have a history of congestive heart failure, diabetes, and hypertension, and were more likely to smoke. Coronary angiographic variables were similar between the 2 groups. Five-year survival was 75.8% for patients with noncoronary atherosclerosis and 90.2% for those without (p < 0.001). The adjusted relative risk of death was 1.7 for any noncoronary atherosclerosis, 1.5 for lower extremity disease alone, 1.7 for cerebral disease alone, and 2.3 for both conditions. Among the 303 patients with noncoronary atherosclerosis, the adjusted relative risk of death for surgery versus angioplasty was 0.87 (p = 0.40). However, the study has limited power to detect a treatment effect in this small subgroup. Thus, patients with combined coronary and clinically evident noncoronary atherosclerosis are a high-risk group with significantly worse long-term outcome compared patients with isolated coronary disease.
Am J Cardiol 1998 Feb 15
PMID:Long-term prognostic value of clinically evident noncoronary vascular disease in patients undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI). 948 22

Through a prospective controlled study of 81 non-selected patients with acute cerebral ischemia, admitted to the hospital over the period of one year, anticardiolipin antibodies (IgG and IgM) were compared to a control group with the objective of evaluating their place as independent risk factors for stroke. Stroke patients' anticardiolipin antibodies (ACA) were again measured at 6 months and compared to the initial values. At the time of the acute ischemic event, the patients' mean ACA IgM was significantly higher than that of the controls and, at 6 months, the patients' mean ACA IgG and IgM were significantly lower than at the time of stroke. Furthermore, through logistic regression analysis and taking into account all other stroke risk factors present in the patient population, ACA IgM's association with stroke was statistically significant. We conclude that ACA may have a role in the pathogenesis of acute cerebral ischemia. Their cross-reactivity with anti-oxidised LDL antibodies may constitute a link between atherosclerosis and thrombosis.
Rev Port Cardiol 1998 Jun
PMID:[Anticardiolipin antibodies in patients with cerebral vascular accident]. 967 30

Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.
J Mol Cell Cardiol 1998 Oct
PMID:Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats. 982 20

Calcium channel blockers constitute a very important group of drugs that are commonly used in the treatment of cardiovascular and cerebrovascular disorders. Current indications for these medications include hypertension, angina, supraventricular arrhythmias, and prevention of coronary and cerebral vasospasm. Although calcium channel blockers originally held great promise in the treatment of myocardial and cerebral ischemia, clinical results have been discouraging. An understanding of the basic physiological mechanisms of actions for these drugs is important for the practising clinician and may explain the disappointing results for the treatment of ischemia to date. This paper is a narrative review, from a clinician's viewpoint, of the structure and role of calcium channels in cardiac and cerebrovascular tissues, as well as a review of the in vitro and clinical results of calcium channel blockade in myocardial and cerebral ischemia.
Can J Cardiol 1999 Mar
PMID:Calcium channel blockers in myocardial and cerebral ischemia: a clinician's review from bench to bedside. 1020 97

To prevent recurrent strokes and transient ischemic attacks, considerable attention is devoted to investigating the etiology of acute cerebral ischemia in the large subpopulation of patients without an easily identifiable cause. In general, transthoracic echocardiography is an insensitive tool for the evaluation of patients with cerebral ischemia, unless clinical signs and/or symptoms of cardiac disease are present. Transesophageal echocardiography (TEE), because of its increased sensitivity for aortic arch atheromata, atrial septal pathology, left atrial thrombi, and valvular abnormalities, is the preferred cardiac imaging modality, especially in young patients, older patients with hypertension or systemic atherosclerosis, and patients with prosthetic heart valves. This paper reviews the prognostic and therapeutic impact of TEE in patients with cerebral ischemia, specifically focusing on the ability of information obtained by this technique to alter patient management and improve risk stratification.
Clin Cardiol 1999 Jun
PMID:Transesophageal echocardiography for the evaluation and management of patients with cerebral ischemia. 1037 77

Cerebral blood flow (CBF) and cerebral metabolic activity tend to decrease in old age. The effect of age per se on the regulation of CBF is not readily separated from the effect of age-associated diseases such as atherosclerosis, multi-infarct dementia, and diabetes mellitus, which may lead to an impairment of CBF autoregulation. Stroke may be prevented effectively by antihypertensive treatment in otherwise healthy elderly patients, but care should be taken to prevent overtreatment with consequent cerebral ischemia. The risk of this may be especially great in elderly patients with hypertension who have postural hypotension.
Am J Geriatr Cardiol 1993 Nov
PMID:The Cerebral Circulation in the Elderly: The Influence of Age, Vascular Disease, and Antihypertensive Treatment. 1141 98

Hypercholesterolemia has not traditionally been considered an important risk factor in the pathogenesis of stroke. However, recent studies show that statin therapy significantly reduces ischemic stroke for patients with established coronary artery disease. Statin therapy may reduce stroke through amelioration of precerebral atherosclerosis in the carotid artery and the aorta. Anti-atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur within the blood and in plaque. Statins may also protect against cerebral ischemia through beneficial modulation of the brain endothelial nitric oxide system. Ongoing studies are exploring the role of statin therapy in the primary prevention of stroke and in the prevention of cognitive decline and multi-infarct cerebrovascular disease.
Curr Opin Cardiol 2001 Jul
PMID:Statin therapy and stroke prevention. 1157 82


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