Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We treated a girl aged 3.5 years (15 kg) with ethanol intoxication, using peritoneal dialysis. The blood ethanol concentration was 6.4 g/l (640 mg/dl; 138.9 mmol/l). It was calculated that the child drank a total amount of 67.2 g of ethanol (4.5 g/kg). The spontaneous ethanol elimination rate before peritoneal dialysis was 0.27 g/l (5.86 mmol/l) per hour; during peritoneal dialysis we found an ethanol elimination rate of 0.32 g/l (6.94 mmol/l) per hour, which was lower than expected. In childhood the ethanol elimination rate with peritoneal dialysis is only slightly faster in comparison to the high spontaneous elimination rate. We conclude that treatment of severe ethanol intoxication should include mainly the maintenance of the vital functions and the meticulous control of blood sugar levels and acid-base disturbances, especially in children. Indications for dialysis are complications caused by ethanol and resistant to supportive therapy, such as seizures, metabolic disturbances, persistent hypoglycemia and the possibility of combined intoxication with other dialysable drugs.
 ...
PMID:The value of peritoneal dialysis in the treatment of severe ethanol intoxication in childhood revised. 151 Dec 8

A variety of in vitro data suggest that ethanol interferes with N-methyl-D-aspartate (NMDA)-stimulated calcium ion conductance. This effect occurs at ethanol concentrations in blood associated with acute intoxication in the nontolerant human (less than 50 mM) and may involve its selective action at the strychnine-insensitive glycine binding site on the NMDA receptor complex. Moreover, there are in vitro data showing that glycinergic interventions can attenuate ethanol's inhibitory actions on NMDA-mediated transmission. The relevance of these in vitro findings to the intact animal was tested in an incremental electroconvulsive shock (IECS) paradigm using milacemide, a lipophilic prodrug of glycine. In this paradigm, the influence of milacemide on ethanol's ability to antagonize the electrical precipitation of seizures was tested. Doses of 3.2 and 32.0 mg/kg did not change ethanol's antiseizure efficacy, whereas 320.0 mg/kg potentiated ethanol's antiseizure efficacy. The mechanism of potentiation of ethanol's antiseizure efficacy by milacemide is unknown. Potentiation could result from stimulation of chloride ion conductance in the brainstem by glycine liberated from the lipophilic prodrug and acting at the strychnine-sensitive site. Alternatively, unmetabolized milacemide, which accumulates at the highest administered dose, may antagonize NMDA-mediated neural transmission. The latter explanation would be consistent with a role for receptor-gated calcium ion conductance in the mediation of ethanol's actions.
 ...
PMID:Effects of milacemide, a glycine prodrug, on ethanol's antiseizure efficacy. 153 63

In primary cultures of cerebellar granule cells, activation of the N-methyl-D-aspartate (NMDA) receptor leads to Ca2+ influx. Previous work showed that this response is selectively inhibited by acute exposure to low concentrations of ethanol. The present results demonstrate that the response to NMDA (measured as an increase in intracellular Ca2+ concentration, using fura-2 fluorescence) is significantly enhanced after chronic in vitro exposure of the cells to ethanol (100 mM for 2-4 days; 20 mM for 3 or more days). This enhancement is consistent with an increased number of NMDA receptors, with no change in receptor properties. Specifically, there was no change in the EC50 values for NMDA and glycine or in the magnitude of inhibition of the NMDA response by competitive or uncompetitive antagonists. There was also no change in the ability of acute ethanol to inhibit the NMDA response after chronic exposure of the cells to ethanol. Furthermore, chronic ethanol exposure did not alter depolarization-dependent increases in intracellular Ca2+ observed after exposure of the cells to 30 mM KCl. The data suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function. In the intact animal, such a change may be associated with particular symptoms of ethanol withdrawal, i.e., withdrawal seizures.
 ...
PMID:Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function. 153 16

The ability of [(+-)-5-aminocarbonyl-10,11-dihydro-5H-di-benzo [a,d]cyclohepten-5,10-imine (ADCI) and its structural analogs dizocilipine (MK-801) and carbamazepine to block ethanol withdrawal seizures was tested in mice made physically dependent upon ethanol. Three injections of either ADCI (ranging from 1.0-10.0 mg/kg), dizocilpine (ranging from 0.1-1.0 mg/kg) or carbamazepine (ranging from 17-50 mg/kg) were administered during the first 7 hr of ethanol withdrawal. The severity of ethanol withdrawal seizures was rated during the first 11 hr of withdrawal and again at 24 hr after withdrawal of ethanol. ADCI and dizocilpine suppressed the severity and occurrence of the withdrawal seizures in a dose-dependent fashion, whereas carbamazepine was ineffective in blocking the withdrawal seizures. The relative potencies of dizocilpine, ADCI and carbamazepine in suppressing ethanol withdrawal seizures corresponded with the relative potencies of the compounds in displacing [3H]dizocilpine from mouse cortical membrane preparations. These findings are consistent with the suggestion that blockade of N-methyl-D-aspartate-mediated neurotransmission is an effective treatment for decreasing ethanol withdrawal seizures. ADCI also blocked the occurrence of withdrawal-associated whole body tremors, whereas dizocilpine and carbamazepine were ineffective in blocking the tremors. The doses of ADCI, dizocilpine and carbamazepine that resulted in motor incoordination on an accelerating rotarod task were determined in groups of naive mice. Dizocilpine in doses as low as 0.3 mg/kg produced a decreased ability to remain on the rotarod, whereas ADCI up to 30 mg/kg did not affect rotarod performance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of the effects of the uncompetitive N-methyl-D-aspartate antagonist (+-)-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (ADCI) with its structural analogs dizocilpine (MK-801) and carbamazepine on ethanol withdrawal seizures. 154 74

Eight group-living male monkeys received cocaine (0 to 3.0 mg/kg) individually or as a group. Cocaine suppressed social affiliative behaviors, eating, and drinking (of both alcohol and control solutions). It induced bizarre stereotypies, hypervigilance, panic-like fleeing, enhancement and then suppression of locomotion, and a seizure. Cocaine had little effect on aggressiveness or sexual behavior. Proportion of time spent lying or sitting changed significantly. Cocaine produced severe behavioral abnormality in this social setting.
Drug Alcohol Depend 1992 Feb
PMID:Cocaine, social behavior, and alcohol-solution drinking in monkeys. 155 26

A classical (Mendelian) genetic analysis of responses to ethanol and nicotine was conducted in crosses derived from mouse lines which were selectively bred for differential duration of loss of the righting response (sleep-time) after ethanol. Dose-response curves for these mice, the long- and short-sleep mouse lines, as well as the derived F1, F2 and backcross (F1 x long-sleep and F1 x short-sleep) generations were generated for several measures of nicotine and ethanol sensitivity. Ethanol sensitivity was assessed using the sleep-time measure. Nicotine sensitivity was tested using a battery of behavioral and physiological tests which included measures of seizure activity, respiration rate, acoustic startle response, Y-maze activities (both crossing and rearing activities), heart rate and body temperature. The inheritance of sensitivities to both of these agents appears to be polygenic and inheritance can be explained primarily by additive genetic effects with some epistasis. Sensitivity to the ethanol sleep-time measure was genetically correlated with sensitivity to both nicotine-induced hypothermia and seizures; the correlation was greater between sleep-time and hypothermia. These data indicate that there is overlap in the genetic regulation of sensitivity to both ethanol and nicotine as measured by some, but not all, tests.
 ...
PMID:Classical genetic analyses of responses to nicotine and ethanol in crosses derived from long- and short-sleep mice. 156 Mar 63

Magnetic resonance spectroscopy (MRS) is a flexible tool with real clinical utility. Examples from our experience in over 250 cases of clinical proton MRS are presented. Shorter echo time and reproducible water suppression increases the number of metabolites which can be detected and identified. Case reports illustrate the significance of altered ratios of N-acetylaspartate, choline, total creatine, myo-inositol, glutamate, glutamine, lactate, glucose, ketones, and, as an incidental finding, ethanol. Significant new information has resulted by applying proton MRS in chronic hepatic encephalopathy, diabetes mellitus and severe hypoxic encephalopathy ('near-drowning'). Potentially useful measurements have been made in normal brain maturation, ethanol related diseases, dementia (normal-pressure hydrocephalus), urea cycle defect and neuronal disease presenting as seizures. Metabolite imaging, particularly with proton, is clinically valuable, documenting the heterogeneity of biochemical disorders in seemingly focal lesions. A new method of specific 31-phosphorus--phosphocreatine imaging provides information in partially denervated skeletal muscle and is expected to have applications in brain.
 ...
PMID:Clinical tools for the 90s: magnetic resonance spectroscopy and metabolite imaging. 156 13

Ethanol (EtOH) withdrawal is characterized by a hyperexcitable state that includes anxiety, tremor, muscle rigidity and seizures. The present three experiments examined the effects of EtOH dependence and withdrawal on the acoustic startle response, an easily quantifiable measure of behavioral reactivity to exteroceptive stimuli. Two intensities of startle stimuli, 105 and 120 dB pulses, were presented to rats during chronic EtOH exposure and during EtOH withdrawal. Prepulse inhibition, which is a sensitive measure of sensorimotor gating processes associated with filtering sensory stimulation, was also assessed during chronic EtOH exposure and withdrawal. Prepulse inhibition was induced by the presentation of a weak 80 dB acoustic stimulus 100 ms prior to a 120 dB stimulus pulse. After 14 days of EtOH liquid diet administration the magnitude of responses elicited by 105 and 120 dB startle stimuli was less in ethanol-treated subjects during continued EtOH access than in animals fed a control liquid diet. When EtOH liquid diet treatment was continued for an additional 3-day period and animals were tested 8 h after withdrawal from EtOH, withdrawn animals were more reactive to startle stimuli at both intensities than were animals maintained on the EtOH liquid diet. A time-course experiment with repeated startle testing at 4, 8, and 12 h post-EtOH exposure revealed significant increases in responding to the 105 dB startle intensity at 8 h post-EtOH exposure. The ability of animals to respond to a prepulse stimulus was not affected during chronic EtOH treatment, but was reduced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Responding to acoustic startle during chronic ethanol intoxication and withdrawal. 157 Mar 82

Population studies suggest that seizures occur in chronic alcoholics as an effect of ethanol withdrawal or ethanol toxicity. Our own studies of individuals undergoing inpatient alcohol detoxification revealed a correlation between the number of detoxifications conducted and the probability that the individual will have a seizure disorder. To establish the basis for this association we studied drinking histories, drug use, and related characteristics of 500 individuals, 83 of whom were women, who enrolled in an inpatient detoxification program. Discriminant analyses revealed a direct correlation between average daily alcohol consumption and the prevalence of seizures in the alcoholic individuals studied. This correlation was significant, but it was not as strong as that between seizure prevalence and the number of times an individual underwent inpatient detoxification. This data supports the hypothesis that seizures occur in alcoholics because of a long-term kindling effect of recurrent detoxifications and a more short-term effect of ethanol exposure.
 ...
PMID:Total ethanol consumption as a seizure risk factor in alcoholics. 157 94

The ability of ethanol to antagonize the electrical precipitation of seizures in an incremental electroconvulsive shock paradigm was examined in groups of stressed and control mice. In stressed mice, the dose-response curve for ethanol's antiseizure efficacy was down-shifted and right-shifted relative to controls. These data may have clinical implications with respect to the interaction between stress, ethanol, and proneness to seizures.
 ...
PMID:Ethanol's antiseizure efficacy is reduced by stress. 158 49


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