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)

Administration of AVP and related peptide fragments following ethanol (EtOH) administration has been shown to enhance retention of tolerance to ethanol. The present studies were designed specifically to: (1) examine the influence of AVP given concurrently with EtOH on the development of tolerance to the ataxic and hypothermic effects of EtOH in Long-Evans rats, and (2) to determine if tolerance to these effects develops in Brattleboro rats which are deficient in AVP. In Experiment 1, EtOH (2.5 g/kg, 15% v/v) was administered IP to 2 groups of rats in combination with a SC injection of either AVP (6 micrograms/kg) or an equal volume of saline. Two additional control groups received IP saline injections in combination with either saline or AVP. After 13 days, EtOH-treated rats were significantly more tolerant than saline-treated animals. AVP significantly increased the hypothermic and ataxic effects of EtOH and failed to enhance tolerance development. AVP delayed the extinction of tolerance to the hypothermic (but not the ataxic) effects of ethanol when administered during the extinction phase to rats previously treated with EtOH. In Experiment 2, Brattleboro rats were injected with EtOH or an equivalent volume of saline and tested for ataxia and hypothermia. Rats receiving EtOH failed to demonstrate significant tolerance to either effect of ethanol after 12 treatment days.
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PMID:The role of arginine vasopressin in the development of tolerance to ethanol in normal and Brattleboro rats. 285 44

The development of organophosphorus-induced delayed neurotoxicity (OPIDN) was studied in the European ferret (Mustela putorius furo). A single oral or dermal dose of 250, 500, or 1000 mg tri-o-tolyl phosphate (TOTP)/kg body weight was administered to adult male ferrets. Corn oil served as the vehicle in the oral test and 95% ethanol was the vehicle in the dermal test. At 48 h posttreatment, half the animals in each group were killed by cervical dislocation for assessment of whole-brain neuropathy target esterase (NTE) activity. The remaining 5 animals per group were observed and examined neurologically on a daily basis for a subsequent 54 d. All ferrets dosed dermally with 1000 mg TOTP/kg body weight developed clinical signs characteristic of OPIDN ranging from ataxia to partial paresis. Ferrets administered 250 and 500 mg TOTP/kg body weight via the dermal route displayed variable degrees of hind limb weakness and ataxia. Of the animals dosed orally, only those in the 1000 mg TOTP/kg body weight group showed clinical signs indicative of OPIDN. These signs did not progress beyond mild ataxia. Small amounts of axonal degeneration were noted in the dorsolateral part of the lateral funiculus and in the fasciculus gracilis of spinal cords in ferrets receiving dermal doses of 1000 mg TOTP/kg body weight. Whole-brain neuropathy target esterase activity was also maximally inhibited (46%) in animals receiving 1000 mg TOTP/kg dermally. These results suggest that the ferret is a species that is susceptible to OPIDN.
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PMID:Delayed neurotoxic effects of tri-o-tolyl phosphate in the European ferret. 291 34

Aromatic and heterocyclic esters of 1-methyl-4-piperidinol and 1,4-dimethyl-4-piperidinol and aromatic esters of (dialkylamino)alkanols were prepared and evaluated for antiepileptic activity by the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (scMet) assays and for minimal central neurotoxicity by the rotorod ataxia test. The most potent compound, namely the 2-phenylbenzoate (57) of 3-(diethylamino)propanol, was slightly more potent than diphenylhydantoin in the MES assay, while the 2-phenylbenzoate (24) of 1-methyl-4-piperidinol and the 2-phenylbenzoate (56) of (diethylamino)ethanol displayed activity comparable to that of diphenylhydantoin. The 2-phenethylbenzoate ester (6) of 1-methyl-4-piperidinol exhibited one-third the activity of diphenylhydantoin. The 2,4,5-trimethylbenzoate 40 and 2,4,6-trimethylbenzoate 41 of 1-methyl-4-pieridinol were even less potent, but did display activity in the phenobarbital-methsuximide range. Certain compounds interact with sites associated with the GABA receptor-chloride channel complex, but their potencies as anticonvulsant agents do not correlate with interaction at sites on the channel complex. Certain analogues antagonize binding of a batrachotoxin analogue to sodium channel sites, a property indicative of local anesthetic activity. There are structural similarities between 2-phenylbenzoates 57, 56, and 24 and diphenylhydantoin, and the latter anticonvulsant also antagonizes binding of the batrachotoxin analogue.
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PMID:Anticonvulsant activity of piperidinol and (dialkylamino)alkanol esters. 301 69

Ethanol, a highly lipid-soluble compound, appears to exert its effects through interactions with the cell membrane. Cell membrane alterations indirectly affect the functioning of membrane-associated proteins, which function as channels, carriers, enzymes and receptors. For example, studies suggest that ethanol exerts an effect upon the gamma-aminobutyric acid (GABA)-benzodiazepine-chloride ionophore receptor complex, thereby accounting for the biochemical and clinical similarities between ethanol, benzodiazepines and barbiturates. The patient with acute ethanol poisoning may present with symptoms ranging from slurred speech, ataxia and incoordination to coma, potentially resulting in respiratory depression and death. At blood alcohol concentrations of greater than 250 mg% (250 mg% = 250 mg/dl = 2.5 g/L = 0.250%), the patient is usually at risk of coma. Children and alcohol-naive adults may experience severe toxicity at blood alcohol concentrations less than 100 mg%, whereas alcoholics may demonstrate significant impairment only at concentrations greater than 300 mg%. Upon presentation of a patient suspected of acute ethanol poisoning, cardiovascular and respiratory stabilisation should be assured. Thiamine (vitamin B1) and then dextrose should be administered, and the blood alcohol concentration measured. Subsequent to stabilisation, alternative aetiologies for the signs and symptoms observed should be considered. There are presently no agents available for clinical use that will reverse the acute effects of ethanol. Treatment consists of supportive care and close observation until the blood alcohol concentration decreases to a non-toxic level. In the non-dependent adult, ethanol is metabolised at the rate of approximately 15 mg%/hour. Haemodialysis may be considered in cases of a severely ill child or comatose adult. Follow-up may include referral for counselling for alcohol abuse, suicide attempts, or parental neglect (in children). The ethanol withdrawal syndrome may be observed in the ethanol-dependent patient within 8 hours of the last drink, with blood alcohol concentrations in excess of 200 mg%. Symptoms consist of tremor, nausea and vomiting, increased blood pressure and heart rate, paroxysmal sweats, depression, and anxiety. Alterations in the GABA-benzodiazepine-chloride receptor complex, noradrenergic overactivity, and hypothalamic-pituitary-adrenal axis stimulation are suggested explanations for withdrawal symptomatology.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute ethanol poisoning and the ethanol withdrawal syndrome. 304 Dec 44

The effect of i.v. administration of ionophores on metabolism in ruminants was investigated in two experiments. In Exp. 1, four Angus heifers were assigned randomly to receive i.v. monensin (18 mg, n = 2) or vehicle (control, n = 2). Samples were collected from indwelling vena cava cannulas from -60 to 240 min. Concentrations of K, Mg (P less than .05) and P (P less than .10) were lower and glucose (GLU) and free fatty acids (FFA) were higher (P less than .05) in monensin-treated than in control heifers. Serum insulin (INS) initially declined and subsequently increased (P less than .05) following monensin administration. A second experiment was conducted to determine the effect of a higher dose of monensin and the effect of lasalocid on minerals and metabolites. Angus (n = 3) and Hereford (n = 3) steers were randomly assigned to treatments in two 3 x 3 latin square designs. Treatments were i.v. administration of monensin, lasalocid or vehicle (ethanol) administered on three consecutive days. Administration of monensin, but not vehicle or lasalocid, resulted in ataxia, hypernea, polyuria and anorexia for approximately 2 h. Plasma concentrations of K, P and Mg were suppressed (P less than .05) by monensin, but not by vehicle or lasalocid administration. The decrease in K was preceded by a transient increase in K 15 min after administering monensin. Concentrations of GLU and FFA increased (P less than .05) following monensin administration. Concentrations of INS were lower from 60 to 120 min and greater at 180 and 240 min compared with -60 to 0 min from monensin administration (P less than .05). These results provide first evidence of an effect of monensin on metabolism in ruminants independent of alterations in ruminal microbial metabolism.
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PMID:Intravenous administration of ionophores in ruminants: effects on metabolism independent of the rumen. 304 32

Rats exposed to ethanol in utero were assessed for changes in gait at 55 days of age. Ethanol-exposed animals had significantly shorter stride lengths, more open step angles, and less gait symmetry than control rats. There were no differences in stance width or apparent speed. This pattern of changes in motor function indicates that prenatal exposure to ethanol produces long-lasting "ataxia" in rats. These results closely resemble previous findings of altered gait following neonatal ethanol exposure in rats, as well as clinical findings in some FAS children. The results are consistent with an hypothesis of prenatal ethanol-induced disruption of functional hippocampal and/or cerebellar development. Ataxia and gait dysfunction may be sensitive indicators of ethanol teratogenesis.
Alcohol
PMID:Prenatal ethanol alters gait in rats. 324 87

Recently, we reported that a chronic regimen of ethanol by intubation, which produced clear tolerance to ethanol-induced hypothermia, ataxia and sleep, produced only a marginal degree of cross-tolerance to these effects of pentobarbital. The present experiments were designed to test the reverse process by examining cross-tolerance to pentobarbital after chronic pretreatment with ethanol, chronic pentobarbital treatment by gavage conferred clear cross-tolerance to both barbital- and ethanol-induced hypothermia, ataxia and sleep. In a separate experiment, cross-tolerance to barbital- and ethanol-induced hypothermia and ataxia was demonstrated over a wide range of test doses. Determination of ethanol blood levels as well as a complete time course of absorption, distribution and elimination of ethanol suggested that pharmacokinetic alterations may play a role in the development of cross-tolerance to ethanol in pentobarbital-treated subjects. The asymmetry of cross-tolerance raises the possibility that pentobarbital and ethanol invoke tolerance by mechanisms that are not wholly identical. This possibility requires further exploration. Conceivably the actions of ethanol which mediate the measured effects form a subset of a larger range of pentobarbital actions that could provide a stronger stimulus to tolerance development.
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PMID:Effect of chronic pentobarbital treatment on the development of cross-tolerance to ethanol and barbital. 325 49

Sons and daughters of male alcoholics were compared with the sons and daughters of controls on two measures of static ataxia. Increased sway was seen in the children of the alcoholic fathers who had an average of 3.7 first- and second-degree relatives meeting criteria for alcoholism. The possibility that static ataxia may be a psychobiological marker for the more genetically mediated variant of alcoholism is discussed.
Alcohol Clin Exp Res 1987 Aug
PMID:Static ataxia as a psychobiological marker for alcoholism. 330 4

Eleven alcoholics with cerebellar degeneration (eight with computerized tomography confirmation of cerebellar atrophy) were matched with nonataxic alcoholics and nonalcoholics. There were no laboratory or physiological markers for ataxia, including hemoglobin A1a + b, red blood cell transketolase, liver function enzymes, and measures of reaction time and hand-eye coordination. Acetaldehyde-modified hemoglobin levels (as hemoglobin A1a + b) did not, as previously reported, distinguish between alcoholics and nonalcoholics. There was 24% less annual alcohol consumption in ataxic alcoholics compared with nonataxic alcoholics, 9% less lifetime consumption in ataxic alcoholics, and 33% less maximal daily intake. The finding that ataxic alcoholics do not have higher alcohol consumption than nonataxic alcoholics suggests that alcoholic cerebellar degeneration is not a dose-dependent phenomenon, and that alcoholics with cerebellar degeneration may have an idiosyncratic sensitivity to the neuronal effects of alcohol.
Alcohol Clin Exp Res 1987 Aug
PMID:Alcoholic cerebellar degeneration is not a dose-dependent phenomenon. 330 8

In the present study, we compared phenotypic differences in behavioral and neurophysiological responses to acute ethanol administration among six inbred rat strains. Genetic variation was found both for ataxia, as measured by loss of righting response (sleep time) after a hypnotic dose of ethanol, and for the depressant action of ethanol on the spontaneous discharge of cerebellar Purkinje neurons. Results from an analysis of covariance of these phenotypes, measured among the inbred strains, provided strong evidence for a high genetic correlation between sleep time and inhibition of cerebellar Purkinje neuron discharge in response to acute ethanol administration. However, ethanol metabolism was also found to correlate with the behavioral sensitivity of rats to ethanol. Preliminary data from the third generation of replicate lines of rats currently being selectively bred for high and low acute sensitivity to ethanol shows a trend toward divergence of both ethanol sleep time and neuronal sensitivity to acute ethanol. The conclusion from these data supports the hypothesis that the cerebellum is an important locus of ethanol action, and suggests that neuronal sensitivity to ethanol will continue to diverge between these rat lines as selection for the sleep time phenotype progresses.
Alcohol Clin Exp Res 1987 Oct
PMID:Genetic correlation of ethanol-induced ataxia and cerebellar Purkinje neuron depression among inbred strains and selected lines of rats. 331 67


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