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)

The effect of the methylxanthines caffeine, theophylline and isobutylmethylxanthine (IBMX) on ethanol-induced ataxia and loss of righting reflex was investigated in three strains of mice. A significant potentiation of ethanol-induced ataxia was produced in all strains of mice at 20, 45 and 75 min after ethanol in mice pretreated with 62.5 mg/kg caffeine and 12.5 mg/kg IBMX. In mice pretreated with 40 mg/kg caffeine potentiation of ethanol-induced ataxia was observed only at 20 min after ethanol. Theophylline pretreatment produced no alteration in ethanol-induced ataxia. The results of methylxanthine pretreatment on ethanol-induced ataxia were similar, regardless of a shorter (10 min) or longer (75 min) pretreatment time. The methylxanthines produced no effect on motor coordination or behavior when administered separately. Although ethanol-induced loss of righting reflex was shortened by theophylline, neither caffeine nor IBMX altered the duration of loss of righting reflex. It is possible that inhibition of adenosine uptake, a known effect of the methylxanthines, may be a more likely explanation for the modulation of the behavioral effects of ethanol.
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PMID:Behavioral interactions of ethanol and methylxanthines. 243 67

The presentation and treatment of a central hypoventilation syndrome in a boy with pyruvate dehydrogenase complex (PDHC) deficiency are reported. Dephosphorylated PDHC was assayed in disrupted fibroblasts after pretreatment with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor. Maximal specific activity of activated patient PDHC was 10% to 30% of control values. Patient PDHC activity was not increased by alterations in concentrations of pyruvate or cofactors (thiamine pyrophosphate [TPP], coenzyme A [CoA], oxidized form of nicotinamide adenine dinucleotide [NAD+]). Clinically, normalization of plasma lactate by a high-lipid diet did not prevent slowly progressive neurologic decline. The patient manifested intermittent ataxia, episodic profound weakness, moderate psychomotor retardation, ophthalmoplegia, and retinal pigment epithelial changes. A true central hypoventilation syndrome was documented on the basis of rigorous radiologic, electrophysiologic, and pulmonary function criteria. Theophylline, progesterone, and ritalin neither altered ventilatory response to CO2 nor permitted weaning from the ventilator. In contrast, peripheral chemoreceptor stimulants (intravenous doxapram; oral almitrine) effected an acute doubling of minute ventilation with appropriate decreases in PaCO2. However, a positive response to long-term therapy with almitrine could not be unequivocally shown. It was concluded that measurement of disrupted fibroblast PDHC following dichloroacetate activation constitutes an accurate assay for PDHC deficiency. PDHC deficiency must be considered in the differential diagnosis of the central hypoventilation syndrome; this appears to be the first report of such an association. Finally, a therapeutic trial of a peripheral chemoreceptor agonist is warranted in the management of central hypoventilation syndrome.
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PMID:Central hypoventilation syndrome in pyruvate dehydrogenase complex deficiency. 643 1

The actions of the alpha 2-antagonist yohimbine and methylxanthines aminophylline and caffeine were evaluated in reversing ataxia, increase in landing foot splay (LFS), produced by the alpha 2-agonist medetomidine in male rats. Medetomidine at 0.1 and 0.15 mg/kg, i.p. increased LFS by 42.9 and 69.6%, respectively. The peripherally acting alpha 2-agonist ST91 (0.125 to 0.5 mg/kg, i.p.) did not significantly affect the LFS. Intraperitoneal injection of yohimbine at 0.5 and 1 mg/kg, aminophylline at 25, 50 and 100 mg/kg, and caffeine at 25 and 50 mg/kg significantly antagonized medetomidine (0.15 mg/kg, i.p.)-induced ataxia. Yohimbine was more effective (100 and 111%) than the methylxanthines (28 to 72%) in reversing medetomidine ataxia. Aminophylline and caffeine, but not yohimbine, significantly reduced LFS in non-medetomidine treated rats. The data suggested that medetomidine ataxia in rats could be specifically antagonized by yohimbine and to a lesser extent by aminophylline and caffeine.
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PMID:Antagonism of medetomidine-induced ataxia in rats by yohimbine, aminophylline and caffeine. 809 78