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

The effect of a single oral 750 mg/kg dose of tri-o-cresyl phosphate (TOCP) on the endogenous phosphorylation of brain and spinal cord proteins was assessed in hens during the development of and recovery from delayed neurotoxicity. Crude membrane and cytosolic fractions were prepared from the brains and spinal cords of control and TOCP-treated hens at 1, 7, 14, 21, 35, and 55 days after treatment. Brain and spinal cord protein phosphorylation with [gamma-32P]ATP was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), autoradiography, and microdensitometry. TOCP administration conferred calcium and calmodulin dependence on the phosphorylation of a few brain cytosolic proteins and caused an increase in the phosphorylation of a number of other cytosolic and membrane proteins. This effect of TOCP was large in magnitude, and its time course reflected the onset of and recovery from the signs of ataxia and paralysis associated with delayed neurotoxicity in the hen. The molecular weights (Mr) and maximal phosphorylation (percent of control) for the most prominently affected bands were as follows: brain cytosol--50K (183%), 55K (575%), 60K (529%), 65K (273%), and 70K (548%); brain membranes--50K (622%) and 60K (697%); and spinal cord cytosol--20K (182%). The role of endogenous phosphorylation reactions in and their potential usefulness as biochemical indicators of delayed neurotoxicity are being explored further.
 ...
PMID:Changes in in vitro brain and spinal cord protein phosphorylation after a single oral administration of tri-o-cresyl phosphate to hens. 404 64

The effect of methyl isobutyl ketone (MiBK) on n-hexane-induced neurotoxicity was investigated via inhalation in seven groups of five hens each for 90 days followed by a 30-day observation period. One group was exposed to vapors containing 1000 ppm n-hexane and another group to vapors having 1000 ppm MiBK. Four groups were exposed simultaneously to 1000 ppm of n-hexane and 100, 250, 500, or 1000 ppm MiBK. Another group was exposed similarly to ambient air in an exposure chamber and used as a control. Hens continuously exposed to 1000 ppm MiBK developed leg weakness with subsequent recovery, while inhalation of the same concentration of n-hexane produced mild ataxia. Hens exposed to mixtures of n-hexane and MiBK developed clinical signs of neurotoxicity, the severity of which depended on the MiBK concentration. Thus, all hens exposed to 1000 ppm n-hexane in combination with 250, 500, or 1000 ppm MiBK progressed to paralysis. Hens continuously exposed to 1000/100 n-hexane/MiBK showed severe ataxia which did not change during the observation period. The neurologic dysfunction in hens exposed simultaneously to n-hexane and MiBK was accompanied by large swollen axons and degeneration of the axon and myelin of the spinal cord and peripheral nerves. The results indicate that the nonneurotoxic chemical MiBK synergized the neurotoxic action of the weak neurotoxicant n-hexane since the coneurotoxicity coefficient for joint exposure was more than two times the additive effect of each treatment alone. In another experiment, to investigate the mechanism of MiBK synergism of n-hexane neurotoxicity, continuous inhalation for 50 days of 1000 ppm n-hexane had no effect on hen hepatic microsomal enzymes, whereas inhalation of 1000 ppm MiBK for 50 days or a mixture of 1000 ppm of each of n-hexane and MiBK for 30 days significantly induced aniline hydroxylase activity and cytochrome P-450 contents in hen liver microsomes. Liver microsomal proteins from these hens and from hens treated with beta-naphthoflavone (beta-NF) and phenobarbital (PB) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. While beta-NF increased the 55-kDa band (1408%), PB, MiBK, and MiBK/n-hexane increased the protein band (49 kDa) (258, 335, and 253%, respectively), indicating that MiBK induces chicken hepatic cytochrome P-450. The results suggest that the synergistic action of MiBK on n-hexane neurotoxicity may be related to its ability to induce liver microsomal cytochrome P-450, resulting in increased metabolic activation of n-hexane to more potent neurotoxic metabolites.
 ...
PMID:The synergism of n-hexane-induced neurotoxicity by methyl isobutyl ketone following subchronic (90 days) inhalation in hens: induction of hepatic microsomal cytochrome P-450. 404 11

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.
 ...
PMID:Genetic influences on the central nervous system depressant and membrane-disordering actions of ethanol and sodium valproate. 609 2

Inflammatory processes were provoked in 35 rats by subcutaneous implantation of sterile cotton-wool pads and treated five days by means of various antiphlogistic substances. The action of sodium salicylate (administered alone or in conjunction with gamma-globulin or with glucose) proved similar to that of prednisolone which was given as control substance. Human gamma-globulin exhibited neither anti-inflammatory nor pro-inflammatory effects. Experiments with twelve rabbits revealed that the pyretogenic potential of sodium nucleinate, one per cent (0.01 g/kg body weight) was stronger than that of animal charcoal or peptone. Yet, the two latter substances may be used, as well. The antipyretic effect of sodium salicylate was not as intensive but just as reliable as that of aminophenazone, when both preparations were applied to rabbits with induced fever. Concomitant administration of glucose is recommended to prevent development of undesired side-effects, such as giddiness or ataxia.
 ...
PMID:[Antiphlogistic and antipyretic effect of sodium salicylate in rats and rabbits]. 616 73

Nifedipine and verapamil injected into the cerebral ventricles of unanaesthetized cats produced a longlasting rise in the body temperature. The hyperthermic effect of nifedipine and verapamil were not dose-dependent. The hyperthermic effect of verapamil was preceded by a shortlasting fall in the body temperature, which was not dose-dependent. Calcium antagonists, nifedipine and verapamil also produced mydriasis, tachypnoea, dyspnoea, ataxia, tremor and muscular weakness. These symptoms were inconsistent and of slight intensity. In agreement with the theory of ionic set point controlling the body temperature, the most probable explanation is that calcium antagonists, nifedipine and verapamil produced changes in the body temperature by acting on sodium and calcium fluxes in the posterior hypothalamus.
 ...
PMID:[Effects of nifedipine and verapamil on body temperature in cats]. 624 Oct 13

The symptoms of poisoning caused by pyrethroids are characterized by ataxia, loss of coordination, hyperexcitation, convulsions, and paralysis. Depending on the type of pyrethroid, repetitive discharges and/or conduction block are observed in various regions of the nervous system. Type I pyrethroids as represented by allethrin and tetramethrin which lack a cyano group cause repetitive discharges in nerve fibers and nerve terminals leading to hyperexcitation of the animal. Type II pyrethroids as represented by cyphenothrin, deltamethrin and fenvalerate which contain a cyano group at the alpha-carbon cause nerve membrane depolarization and block leading to paralysis of the animal. Both types of action are ascribed to modifications of nerve membrane sodium channels which result in very slow gating kinetics. Patch clamp single channel recording experiments have clearly demonstrated that individual sodium channels are modified by tetramethrin in an all-or-none manner to give rise to a prolonged opening without change in conductance. Thus, it is concluded that the site of action of pyrethroids is the sodium channel, and that pyrethroids interact with the channel macromolecules that control the gating mechanism.
 ...
PMID:Cellular and molecular mechanisms of action of insecticides: neurophysiological approach. 630 35

In a previous study it has been shown that sodium diphenyl hydantoinate is effective in preventing electrically induced convulsive seizures in cats. The drug is relatively nontoxic and well tolerated by the usual laboratory animals. A clinical trial of sodium diphenyl hydantoinate was made in 200 patients with frequent convulsive seizures which had not been relieved by the previous modes of therapy. In 142 such patients who have received the treatment for periods varying from two to eleven months, grand mal attacks were relieved in 58 per cent and greatly decreased in frequency in an additional 27 per cent; petit mal attacks were relieved in 35 per cent and greatly decreased in frequency in an additional 49 per cent, and psychic equivalent attacks were relieved in 67 per cent and greatly decreased in frequency in 33 per cent. There were no fatalities. A toxic dermatitis occurred in ten patients (5 per cent), nonthrombocytopenic purpura in one patient and minor (in many instances, transient) toxic reactions, tremors, ataxia, dizziness and the like in approximately 15 per cent.
 ...
PMID:Landmark article Sept 17, 1938: Sodium diphenyl hydantoinate in the treatment of convulsive disorders. By H. Houston Merritt and Tracy J. Putnam. 636 36

The hypothesis was tested that sedation and stereotyped behaviour, developing in rats after the administration of the steroid derivative with gamma-aminobutyric acid (GABA) antagonistic properties, R 5135, are of an epileptiform nature. Electroencephalographic (EEG) and visual evoked potentials (VEP) were recorded and behaviour was observed over not less than 5-7 hr after subconvulsive doses of R 5135. Doses of 2-4 mg/kg of the compound produced quasi-rhythmic spikes resembling experimental focal epileptic discharges in all rats. This epileptiform activity was accompanied by behavioural sedation and somnolence, followed by a build-up of stereotyped behaviour and sporadic episodes of epileptiform motor activity, developing 1-2 hr after injection. The secondary components (SNW) of the visual evoked potentials were suppressed by R 5135 and the primary potential (N1) facilitated, virtually reducing the visual evoked potential to the form of an evoked spike. Pretreatment with the anticonvulsant GABAergic drugs gamma-acetylenic GABA (GAG) (100 mg/kg), sodium valproate (VPA) (400 mg/kg) and diazepam (5 mg/kg) suppressed the motor components of seizure activity, producing severe ataxia, but not the electrographic manifestation of seizure activity. Neither gamma-acetylenic GABA nor valproate significantly altered the latency to onset of spiking, although all three drugs did significantly reduce the frequency of discharges. Diazepam was the only anticonvulsant tested which completely suppressed spike activity in 3 of 5 rats. Moreover, R 5135 was found to antagonize diazepam, but not valproate induced suppression of secondary components of the visual evoked potential, suggesting that diazepam and R 5135 may compete for the same receptor.
 ...
PMID:Regular and lasting neocortical spiking produced by systemic administration of a steroid derivative in the rat. 640 88

A male newborn infant presented with metabolic acidosis and haemolytic anaemia. Renal tubular acidosis was suspected in the absence of amino aciduria and the patient was treated with sodium bicarbonate. Two years later, the chronic acidosis, clinical observation of developmental delay and ataxia prompted further investigational studies. 5-Oxoprolinuria was identified by gas-liquid chromatography and confirmed by mass spectrometry after an initial mass spectrum analysis reported a glutamic acid artifact. Glutathione and glutathione synthetase in erythrocytes were 25% and 5% of control values, respectively. On the basis of neonatal metabolic acidosis, without amino aciduria and an elevated reticulocyte count, a recommendation is made for blood glutathione and urine 5-oxoproline screening, followed by glutathione synthetase assay for confirmation of neonatal 5-oxoprolinuria.
 ...
PMID:Neonatal 5-oxoprolinuria: difficult-to-diagnose? 640 9

The clinical and clinicopathologic effects of excess oral pyridoxine hydrochloride (150 mg/kg body weight/day) and clioquinol (200 mg/kg body weight/day) alone and in combination were evaluated in adult Beagle dogs over an experimental period of approximately 100 days. Anorexia and loss of body weight occurred in the first weeks of the trial period in each treatment group, but was most severe in dogs given both compounds. Dogs in each treatment group (10 of 10 pyridoxine-treated dogs, 6 of 13 clioquinol-treated dogs and 12 of 13 pyridoxine plus clioquinol-treated dogs) developed neurologic disease, manifested principally by ataxia. Pyridoxine-treated dogs had proprioceptive loss involving both fore- and hindquarters, characterized by stiff, spastic, dysmetric leg movements. In clioquinol-treated dogs, dysmetric leg movements were accompanied by failure to support body weight in the hindquarters, but similar forelimb involvement occurred in severely affected dogs. The neurologic disease in dogs given both compounds varied; signs in some dogs resembled those of affected dogs of the pyridoxine-treated group, and in others, those in clioquinol-treated group. Erythrocyte counts, hemoglobin concentrations and packed cell volumes were reduced in dogs in each treatment group and were lowest in dogs given both compounds. Plasma protein was mildly reduced in dogs given pyridoxine or pyridoxine plus clioquinol. Few or no differences were present in the leukocyte counts, blood urea nitrogen concentrations, in activities of serum alanine aminotransferase and aspartate aminotransferase, and in concentrations of sodium, chloride or potassium in treated dogs as compared to control dogs.
 ...
PMID:The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs. I. Clinical disease. 645 37


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