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 interactions of caffeine (10 mg/kg p. o.) with various doses of ethanol, diazepam or pentobarbital were investigated by observing the ambulatory activity of mice. The ambulatory activities after the coadministration of caffeine with ethanol (1.6, 2.4 and 3.2 g/kg p. o.) were significantly higher than those after the single administration of the corresponding doses of individual drugs. Ethanol alone significantly increased the activity with ataxia at 2.4 and 3.2 g/kg, suggesting that 1.6 g/kg of ethanol was an optimum dose for studying the interaction of caffeine with ethanol. Although diazepam (0.25, 0.5 and 2 mg/kg s. c.) and pentobarbital (1, 3 and 10 mg/kg s. c.) alone did not change the activity, they significantly reduced the effect of caffeine. Naloxone (1 and 5 mg/kg s. c.) did not modify the effect of caffeine alone, but, at 5 mg/kg, it was effective in significantly reducing the ambulation-increasing effect of caffeine with ethanol (1.6 g/kg) to nearly the level of caffeine alone. Ca-cyanamide (5 mg/kg p. o., pretreatment 30 min before), reserpine (1 mg/kg s. c., pretreatment 4 hr before) and alpha-methyl-p-tyrosine (200 mg/kg i. p., pretreatment 1 hr before) reduced the ambulation increment induced by caffeine alone or combination of caffeine with ethanol. Ethanol, diazepam and pentobarbital are classified as CNS depressants, and caffeine as a CNS stimulant. However, the present experiment demonstrated that the interaction of caffeine with ethanol was very different from that of caffeine with diazepam or pentobarbital. In the enhancing interaction of caffeine and ethanol, both dopaminergic and endogenous opioid systems may be involved.
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PMID:Ethanol enhances, but diazepam and pentobarbital reduce the ambulation-increasing effect of caffeine in mice. 144 12

Characteristics of the ambulation-increasing effect of MK-801, a non-competitive NMDA antagonist, were assessed through the coadministration of MK-801 with various central-acting drugs in mice. The MK-801 (0.3 mg/kg, i.p.)-induced ambulation-increment with a slight ataxia was maximum at around 50 min, and ambulation returned to the control level at about 3 hr after the administration. At 1 mg/kg, the mouse's activity transiently increased, followed by a decrease due to a marked ataxia, which was due to neither stereotypy nor convulsion, for 20-50 min, and then increased again; the ambulation-increment continued even at 4 hr after the administration. Coadministration of MK-801 (0.3 mg/kg, i.p.) with either methamphetamine (2 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), GBR-12909 (10 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) or morphine (10 mg/kg, s.c.) produced a significant enhancement of the effect. However, 0.1 mg/kg of MK-801 had no effect on the interaction with these drugs. On the other hand, the ambulation-increasing effect of MK-801 (0.3 mg/kg) was significantly reduced by haloperidol (0.3 and 0.1 mg/kg, s.c.), ceruletide (0.01 and 0.1 mg/kg, i.p.), reserpine (0.05 and 2 mg/kg, s.c., pretreatment 4 hr before) and nimodipine (1 and 3 mg/kg, i.p.), but it was scarcely modified by alpha-methyl-p-tyrosine (100 and 200 mg/kg, i.p., pretreatment 24 hr and 4 hr before), imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydro-biopterin (100 mg/kg, i.p.), pilocarpine (1 and 4 mg/kg, s.c.), N6-(L-2-phenylisopropyl)-adenosine (0.03 and 0.1 mg/kg, s.c.) and naloxone (1 and 5 mg/kg, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of the ambulation-increasing effect of the noncompetitive NMDA antagonist MK-801 in mice: assessment by the coadministration with central-acting drugs. 164 Jun 58

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 neuromodulators, adenosine, serotonin, and glycine, did not alter the course of hepatic encephalopathy (HE) that followed a portacaval shunt and hepatic artery ligation in rats. The substances were instilled into the brain ventricle through an intraventricular cannula in doses that affect other aspects of behavior in the normal rat (adenosine, suppression of food intake; serotonin, loss of muscle strength and ataxia; glycine, leaning and circling). A subconvulsive dose of the glycine antagonist, strychnine, also had no effect on the course of HE. A large dose of the adenosine antagonist, caffeine, had a depressive rather than excitatory effect and shortened the time taken to induction of coma. These studies and a similar previous one with gamma-aminobutyric acid (GABA) suggest that the inhibitory neuromodulators do not have a prominent role in the pathogenesis of hepatic coma.
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PMID:Inhibitory neuromodulators do not alter the course of experimental hepatic encephalopathy. 290 9

The effects of adrenoreceptor blocking agents on corticotropin-releasing factor (CRF)-induced behavioral changes in rats were examined. The i.c.v. injection of 1 micrograms ovine CRF significantly increased the grooming frequency, number of occurrences of rearing and total distance moved. I.c.v. administered phentolamine at a dose of 10 nmol completely suppressed the increase in rearing and total distance moved induced by CRF without affecting the grooming frequency, whereas 100 nmol phentolamine significantly decreased the grooming frequency as well as the rearing and total distance moved. In contrast, propranolol reduced the increase in rearing induced by CRF only at a dose which induced ataxia in rats. The increases in rearing and total distance moved induced by CRF were reduced by 10 nmol of yohimbine and 100 nmol of prazosin. S.c. injection of caffeine (10 mg/kg) produced a significant increase in grooming frequency, rearing, and total movement. Administration of 10 nmol phentolamine and yohimbine did not affect these behavioral changes induced by caffeine, while 100 nmol prazosin suppressed them. Therefore, prazosin depressed the behavior of rats non-specifically. These results suggest that CRF-induced behavioral hyperactivity is mediated at least in part by alpha-noradrenergic, mainly alpha 2-noradrenergic, systems in the brain.
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PMID:Effects of adrenergic blockers on corticotropin-releasing factor-induced behavioral changes in rats. 350

The potentiating effect of caffeine on X-ray-induced chromosomal aberrations in human blood lymphocytes has been investigated, with special reference to cell cycle stages (G0 and G2). Both quantitative and qualitative differences in the yield of chromosomal aberrations were detected in caffeine-posttreated cells, depending on the cell stage irradiated. The studies on caffeine potentiating effects on X-irradiated G0 lymphocytes from normal adults, newborns, Down syndrome patients, and an ataxia telangiectasia patient pointed to interindividual variations in the response to caffeine potentiation among normal probands and a very profound effect in ataxia cells.
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PMID:The effect of caffeine posttreatment on X-ray-induced chromosomal aberrations in human blood lymphocytes in vitro. 644 19

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

Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery of the PDC gene and enable investigators to determine whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus.
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PMID:Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q. 865 18

When cells are exposed to ionizing radiation, they initiate a complex response that includes the arrest of cell cycle progression in G1 and G2, apoptosis and DNA repair. DNA is an important subcellular target of ionizing radiation, but oxydative damage to plasma membrane lipids initiates signal transduction pathways that activate apoptosis and that may play a role in cell cycle regulation. How is DNA damage converted into intracellular signals for cell cycle arrest? The ataxia telangectasia mutant (ATM) protein and/or the DNA-dependent protein kinase (DNA-PK), that are both activated by DNA damage, may initiate cell cycle arrest by activating the p53 tumor suppressor protein. The p53 protein acts as a transcription factor and regulates expression of several components implicated in pathways that regulate cell cycle progression. The best known, p21WAF1/CIP1 protein, is an inhibitor of cyclin-dependent kinases (CDK), a family of protein kinases known as key regulators of cell cycle progression. p21WAF1/CIP1 was shown to be able to inhibit several CDK, but is most effective toward G1/S cyclins. Other CDK inhibitors, p27KIP1 and p15INK4b are activated by irradiation and contribute to the G1 arrest. Moreover, radiation-induced G2 arrest was shown to require inhibitory phosphorylation of the kinase cdc2 via an ATM-dependent pathway. Mutations in cell cycle regulatory genes are common in human cancer and cell cycle regulatory deficiency can lead to increase resistance to ionizing radiation in cancer cells. The major function of p53-dependent G1 arrest may be elimination of cells containing DNA damage whereas G2 arrest following radiation has been shown to be important in protecting cells from death. Cell cycle checkpoints offer a new set of potential targets for chemotherapeutic compounds, especially the G2 checkpoint. Thus, abrogation of the G2 checkpoint with methylxanthines such as caffeine or protein kinase inhibitors such as staurosporine and UCN-01 (7-hydroxystaurosporine) was found to sensitize cells to ionizing radiation. These data did not lead to clinical applications, but confirm targeting of the G2 checkpoint may be an important strategy for cancer therapy.
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PMID:[Cell cycle regulation after exposure to ionizing radiation]. 1034 40

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.
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PMID:Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder. 1131 Jun 26


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