Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral angiography, performed after a seizure in a patient with a life-long history of typical hemiplegic migraine, disclosed markedly dolichoectatic anterior and middle cerebral arteries. No abnormality of the adjacent capillary or venous structures was present. A positive brain scan was attributed to ischemia induced by vasospasm rather than to the corresponding large tortuous anterior and middle cerebral arteries. There were no permanent sequelae and the patient has been free of seizures on Dilantin and phenobarbital over a 3-year follow-up period. Angiographic demonstration or description of a similar ectatic set of anterior and middle cerebral arteries could not be found in the literature. The concurrence of seizures and hemiplegic migraine adds to the peculiarity of this case.
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PMID:Cerebral arterial dolichoectasia with seizure. Case report. 125 41

The 21-aminosteroid antioxidant U-74006F (1) is being developed as an iv injectable agent for the treatment of human CNS trauma and ischemia. Because of its poor water solubility, the plasma compatibility of the parenteral formulation of 1 was evaluated using three models: (I) static solubility, (II) aggregometric, and (III) dynamic flow. The flow model was designed to mimic an iv infusion into the human antecubital vein, which was assumed to have plasma flow of 10 mL/min. Dilantin (phenytoin), the positive control, produced a precipitate in all three models from a 10% (v/v) mixture with human plasma, which approximates the in vivo ratio when the drug is infused at the recommended rate of 1 mL/min. Approximately 39% of the phenytoin dose in the flow model was retained on a downstream 3-microns filter as crystals. In comparison, the parenteral formulation of 1 produced minimal precipitate in models I and II from 40% mixtures with plasma, but higher percentages produced unstable suspensions with time-dependent precipitation. The percentage of the dose of the parenteral formulation of 1 retained on the filter in the flow model was 0.5% or less at infusion rates as high as 10 mL/min and 3% at 19 mL/min. At the 10-mL/min infusion rate, the mass of 1 retained on the filter per minute was less than 1% of the mass of phenytoin retained at the 1-mL/min infusion rate for Dilantin. The acceptable plasma compatibility of the parenteral formulation of 1 appears to be related to the solubilizing effects of plasma protein binding and pH suppression by the citric acid vehicle.
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PMID:Plasma compatibility of injectables: comparison of intravenous U-74006F, a 21-aminosteroid antioxidant, with Dilantin brand of parenteral phenytoin. 186 39

Protection of the brain and spinal cord against ischemia is a goal of vast clinical importance. One approach to this objective is to reduce the tissue's functional activity in order to preserve energy for the metabolic processes that are essential to viability. Experiments to explore ways of reducing function-related energy demands were performed on isolated rabbit retina, a well-characterized model of organized adult mammalian central nervous system (CNS) tissue. The retina was maintained in a nearly physiological state in a miniature "heart-lung" apparatus. Energy metabolism (oxygen consumption and glycolysis) and electrophysiological function (determined by electroretinogram) of the in vitro retina were monitored, and their responses to a series of agents that may reduce energy requirements were determined. Large reversible reductions in O2 consumption, glycolysis, and electrophysiological function were seen in response to mild hypothermia (-3 degrees to -6 degrees C), phenytoin (Dilantin, 100 to 200 mg/kg), chlordiazepoxide (Librium, 200 microM), lithium (1 to 4 mM), Mg++ (6 to 20 mM), strophanthidin (0.15 to 0.25 microM), CO2 (25% to 30%), 2-amino-5-phosphonovaleric acid (APV, 500 microM), amiloride (1 mM), and dantrolene (1 mM). One retina was exposed simultaneously to a combination of six of these agents, which reduced its oxidative and glycolytic metabolism to less than 50% of the control level. The retina recovered metabolic and electrophysiological function after a 2 1/2-hour exposure period. Other agents tested (diphenhydramine, midazolam, nifedipine, nimodipine, and quercetin) had effects on energy metabolism and electrophysiological function that were poorly reversible. Surprisingly little effect was seen in response to general anesthetic agents (thiopental and Althesin) and other CNS depressants (chlorpromazine, ethanol, lidocaine, paraldehyde, valproic acid, and baclofen). The presumed mechanisms through which these agents reduce cellular energy requirements, as well as their potential roles in the treatment of CNS ischemia, are discussed.
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PMID:Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia. 341 90

Phenytoin (diphenylhydantoin, Dilantin, PHT), an anticonvulsant and antiarrhythmic drug, is teratogenic to A/J mice, producing an increased incidence of cleft lip with or without cleft palate [CL(P)] and cardiac defects. Although its mechanism of teratogenic action remains unclear, one possibility may involve uterine ischemia resulting from an exaggerated depressant effect on maternal cardiovascular function. To test this hypothesis, the heart rate response of susceptible A/J and resistant C57Bl/6J mice was monitored following intraperitoneal injection of doses of PHT of known teratogenic potential. Heart rate (HR) was obtained electrocardiographically from unanesthetized, pregnant mice on day 10 of gestation via previously implanted subcutaneous electrodes. The HR of A/J mice was significantly depressed relative to vehicle-injected controls following doses of 40, 60, and 75 mg/kg, with the greatest effect occurring in the high-dose group. In C57Bl/6J mice, the HR response of the group treated with 75 mg/kg was not different from that of the vehicle-treated controls. At the same dose level, the depression of HR of A/J mice was significantly greater in magnitude and duration than that of C57Bl/6J mice. A proposed maternally mediated mechanism of CL(P) in A/J mice involving low placental/embryonic oxygen delivery is discussed. The results of the present study indicate the potential significance that changes in maternal physiology may have on embryonic development.
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PMID:Effect of phenytoin on maternal heart rate in A/J mice: possible role in teratogenesis. 663 88