Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluates multiple aspects of the reaction to two doses of ethanol (0.75 and 1.1 mL/kg) in 30 sons of alcoholic fathers and 30 matched controls with no known alcoholic relatives. Based on results of prior research, the evaluations included the postethanol changes in subjective feelings, levels of body sway or static ataxia, and plasma levels of prolactin and cortisol. A stepwise discriminant function analysis on the sample of 60 men revealed that four items (maximum terrible subjective feelings after high dose, cortisol values at two time points after high dose, and prolactin results after low dose) combined to correctly identify 83% of the controls and 70% of the sons of alcoholics. This included approximately 40% of each group whose discriminant scores were +1 or -1 and who were considered to be solidly classified. These results were relatively robust on a jackknife validation procedure. Results of a search for independent factors in the cluster of test scores after ethanol using a principal components analysis were consistent with the discriminant analysis, indicating the possibility of three overlapping domains of the ethanol response, including subjective feelings after the high-dose ethanol challenge (explaining 46% of the variance), hormonal changes after high-dose ethanol along with body sway items (14% of variance), and prolactin changes after low-dose ethanol (9% of variance). There were few background differences between men who had been properly and improperly classified.
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PMID:A simultaneous evaluation of multiple markers of ethanol/placebo challenges in sons of alcoholics and controls. 342 53

Chronic alcoholics who maintain abstinence often demonstrate remarkable improvement of neurological and mental dysfunction. This paper presents an overview of the clinical and laboratory work of our group. Reversible clinical manifestations include psychometric scores, ataxia, tremor, Parkinsonism, dyskinesia, cerebral atrophy, EEG parameters, and a CSF acidosis. Electrophysiological investigations showed that in the in vitro hippocampus of rats fed ethanol for several months there was evidence for diminished long-term potentiation, impaired neuronal inhibitory mechanisms (diminished inhibitory post-synaptic potentials and post-spike after hyperpolarisations), decreased neuronal specific membrane capacitance and increased specific membrane resistance. Golgi stains showed attenuation of hippocampal CA1 neuronal dendrites in rats fed ethanol for five months, which reverted to control size in rats permitted two months of alcohol withdrawal.
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PMID:Reversibility of alcohol-related brain damage: clinical and experimental observations. 347 66

The assessment of alcoholic brain damage by computerized tomographic (CT) scanning is reviewed and discussed. Alcoholics showed greater cerebral atrophy than aged-matched neurological controls. Supratentorial atrophy measurements correlated significantly with some neurobehavioral assessment measures. The cerebral atrophy reversed in some subjects with maintained abstinence. Computerized assessment of cerebral spinal fluid volume (cerebral atrophy) and mean cerebral density showed decreased cerebral spinal fluid volume and increased cerebral density with maintained abstinence over 4 weeks in a group of 20 alcoholics. CT cerebellar measurements demonstrated atrophy in many subjects, but these measurements did not correlate with measures of ataxia, cognitive impairment, supratentorial atrophy measurements, or age. An example of a magnetic resonance imaging scan of an alcoholic is given. Its advantages in avoiding bony artifact for posterior fossa atrophy estimations and its potential for in vivo description and localization of central nervous system metabolic abnormalities in alcoholism are discussed.
Alcohol Clin Exp Res 1986 Jun
PMID:Computerized tomographic scan assessment of alcoholic brain damage and its potential reversibility. 352 41

In a prospective, uncontrolled study, 62 alcoholic patients received IV phenobarbital (IV-PB) to treat the alcohol withdrawal (AW) syndrome. Initially 260 mg of IV-PB were administered followed by 130 mg every 30 minutes to an end point of light sedation. A mean loading dose of 598 (+/- 192) mg of IV-PB resulted in a mean increase in the serum PB level of 13.9 (+/- 4.7) microgram/mL. Thus, the serum PB level rose 1.65 micrograms/mL for each mg/kg of IV-PB administered to these adult patients in AW. Forty-six of 48 tremulous patients (96%) showed improvement in their AW tremors. None of the 38 patients who presented with AW seizures had another convulsion during a mean observation period of three hours and 47 minutes. Transient ataxia or over-sedation occurred in three of 62 patients (5%) and was exacerbated by concurrent ethanol, diazepam, or phenytoin (six of 17), who were excluded from the study. We conclude that IV-PB is a safe and efficacious therapy for mild to moderate AWS, and IV-PB may prevent AW seizures.
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PMID:Intravenous phenobarbital for alcohol withdrawal and convulsions. 361 62

A chronic regimen of ethanol by intubation, which produced clear tolerance to ethanol-induced hypothermia, ataxia and narcosis, produced only a marginal degree of cross-tolerance to these effects of pentobarbital. The lack of appreciable cross-tolerance to pentobarbital-induced hypothermia and ataxia was also observed over a wide range of test doses. However, cross-tolerance to barbital was observed after chronic treatment with ethanol. Increased rate of drug biotransformation did not contribute significantly to the observed tolerance and cross-tolerance. The difference in the extent of cross-tolerance between ethanol and the two barbiturates is consistent with the hypothesis that there is a degree of specificity in the sites of action of ethanol and other sedative-hypnotic drugs.
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PMID:Tolerance to ethanol and cross-tolerance to pentobarbital and barbital. 371 75

A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clinical evaluation. Our structure-activity relationship (SAR) studies revealed that in addition to the naphthalenyl and phenethylphenyl aryl moieties of nafimidone and denzimol, respectively, fluorenyl, benzo[b]thienyl, and benzofuranyl aryl groups provided several highly active (arylalkyl)imidazole anticonvulsants. These structurally diverse aryl moieties, and comparable anticonvulsant activities, lend credence to the hypothesis that the pharmacophore of this class of anticonvulsants is the alkylimidazole portion of the molecule, with the lipophilic aryl portion enabling penetration of the blood-brain barrier. We focused our SAR studies on the (fluorenylalkyl)imidazole series. A representative compound from this series is 1-(9H-fluoren-2-yl)-2-(1H-imidazol-1-yl)ethanone. This agent was twice as potent as nafimidone in inhibiting maximal electroshock seizures in mice (po ED50's = 25 and 56 mg/kg, respectively) and considerably less toxic in the rat (po LD50's = 4550 and 504 mg/kg, respectively). The tertiary alcohol alpha-(9H-fluoren-2-yl)-alpha-methyl-1H-imidazole-1-ethanol was as potent as denzimol in mice (po ED50's = 10 and 12 mg/kg, respectively). This series of imidazole anticonvulsants was highly selective; while many compounds displayed potent antielectroshock activity, little or not activity was observed against pentylenetetrazole-induced clonic seizures or in the horizontal screen test for ataxia. All active compounds that we tested in this series, as well as denzimol and nafimidone, potentiated hexobarbital-induced sleeping time in mice, probably by imidazole-mediated inhibition of cytochrome P-450. The SAR's for the anticonvulsant activity and the sleeping time potentiation were similar. The propensity of these (arylalkyl)imidazole anticonvulsants to interact strongly with cytochrome P-450 and thereby impair the metabolism of other antiepileptic drugs may severely limit their clinical utility as anticonvulsants.
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PMID:Structure-activity relationships of (arylalkyl)imidazole anticonvulsants: comparison of the (fluorenylalkyl)imidazoles with nafimidone and denzimol. 374 10

Blocks of tissue from the hypothalamus, olfactory bulb, or striatum of rats were incubated in vitro to study the basal and potassium-stimulated release of endogenous catecholamines. When ethanol (100-250 mM) was added to these preparations in vitro no changes in release were observed. When ethanol (3.0 g X kg-1) was injected intraperitoneally in vivo, however, and 3,4-dihydroxyphenylethylamine (DA, dopamine) release was measured in vitro at various times after drug administration, significant increases in the basal release and decreases in the potassium-stimulated release were observed in striatum and olfactory bulb. In striatum, these changes showed a more rapid onset and a longer duration than in olfactory bulb. In both brain regions, DA release did not differ from controls at 4-6 h after the ethanol injection, although blood ethanol concentrations remained elevated. This may imply the tissue's acquisition of acute functional tolerance to the drug. Similar increases and decreases in the basal and the potassium-induced release of DA from striatal tissues were also found at 1 h after injection of a lower dose of ethanol (1.0 g X kg-1). In terms of behavior, this lower dose of ethanol produced only mild intoxication and ataxia, in contrast to the loss of righting reflex following the higher dose.
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PMID:Effects of ethanol in vitro and in vivo on the release of endogenous catecholamines from specific regions of rat brain. 396 14

This study measures the amount of body sway or static ataxia in 34 drinking but nonalcoholic men 21 to 25 years of age who have an alcoholic first-degree relative (the family-history-positive, or FHP, group). Results are compared with 34 control subjects matched pairwise on demographic characteristics and drinking histories, but who have no known alcoholic close relatives (the family-history-negative, or FHN, group). Each man was tested on three occasions where he drank either placebo, or 0.75 mL/kg or 1.1 mL/kg of ethanol; the subjects were repeatedly tested during the subsequent four hours. At the baseline of each of the three test sessions, the level of body sway for the two family-history groups was virtually identical. However, following the 0.75-mL/kg dose, the increase in body sway was significantly less for the FHP than for FHN group, with similar but less dramatic group differences noted following the ingestion of 1.1 mL/kg of ethanol. These results are consistent with the significantly less intense subjective feelings of intoxication after drinking for the FHP men, and also parallel findings of less intense ethanol-related changes in biologic and cognitive test scores. A decreased intensity of reaction to ethanol should be explored further as a possible genetic trait marker of a predisposition toward alcoholism.
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PMID:Ethanol-induced changes in body sway in men at high alcoholism risk. 397 55

Traumatic damage in the posterior fossa is a relatively rare event. A case of a 52-year-old alcoholic is reported who had two severe head traumas during a fight. The subsequent complaints consisted in vertigo and ataxia and were related to a post-commotional syndrome or damage due to chronic alcoholism. The neurological work-up, which was performed a few months later showed typical signs of traumatic damage of the cerebellum. This was confirmed by axial CT-scan.
Drug Alcohol Depend 1985 Jun
PMID:[Traumatic damage of the posterior cranial fossa in chronic alcoholism]. 402 55

The effects of the two central nervous system (CNS) depressant drugs ethanol and sodium valproate were compared using two pairs of mouse lines that had been selected from a heterogeneous stock for differential sensitivity to ethanol. The LS/SS lines differ in sensitivity to ethanol-induced sedation, and the WSP/WSR lines differ in the severity of their withdrawal convulsions after chronic ethanol treatment. We used these lines to test the hypothesis that ethanol and valproate act by the same mechanism. CNS depressant action was assessed by determining the brain drug concentration at which the mice lost their ability to balance on a stationary wooden dowel. LS mice were about twice as sensitive as SS mice to valproate-induced ataxia, in agreement with their reported relative sensitivity to ethanol. The WSR and WSP mice did not differ significantly in sensitivity to ethanol or valproate in this test. The intrinsic order and sensitivity to disordering of synaptosomal plasma membranes prepared from the four lines were measured using fluorescence polarization with the probe 1,6-diphenyl-1,3,5-hexatriene and EPR spectroscopy with 5-doxylstearic acid. No differences in the intrinsic membrane order of the four lines were detected with either technique. The sensitivities of the membranes from the four lines to ethanol- or valproate-induced disordering were not significantly different when measured by fluorescence polarization, but EPR spectroscopy revealed line differences in disordering sensitivity that correlated with the relative sensitivity of the four lines to the CNS depressant action of these drugs. These studies show that genetic factors modulate sensitivity to ethanol and valproate in a similar manner both in vivo and in vitro, suggesting that these drugs act by the same membrane-disordering mechanism.
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PMID:Genetic influences on the central nervous system depressant and membrane-disordering actions of ethanol and sodium valproate. 609 2


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