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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on acute toxicities of pepleomycin sulfate were carried out in both sexes of mice and rats, comparing with bleomycin, and male dogs. Pepleomycin was administered subcutaneously, intravenously and intraperitoneally in both sexes of mice and rats, and intravenously in male dogs respectively. Mice and rats, and intravenously in male dogs respectively. Mice and rats were observed respectively for 10 and 14 days after the administration. LD50 values were calculated by the method of Litchifield & Wilcoxon. LD50 values of pepleomycin were 4 approximately 6 times smaller than those of bleomycin in all routes of mice, but difference between them was not significant in all routes of rats. Additionally sex-difference of LD50 values was scacely recognized in all routes of both species. Toxicological findings observed in common to all routes of both species were ataxia, depression, tremor and epiphora, and only in all routes of mice, head-twitch, running-round and rolling were especially recognized as toxic behavior, which were not observed in bleomycin. Hepatic and renal lesions were recognized in biochemically and histopathologically in the survived rats. The dogs treated with pepleomycin 50 and 30 mg/kg had the decrease in food intake and the loss of body weight. They became moribund in 9 approximately 36 days after administration. In these dogs the lesions of liver and kidney were severely recognized in biochemical and histopathological findings. One of them which received 50 mg/kg recovered biochemically and histopathologically in 209 days after administration by the supplemental nutrition in early stage.
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PMID:[Toxicological studies on pepleomycin sulfate (NK 631). I. Acute toxicity of pepleomycin in mice, rats and dogs (author's transl)]. 8 4

Subchdronic administration of S,S,S-tributyl phosphorotrithioate (DEF) caused 3 toxicologic effects in hens, depending upon route of administration. Small delay oral doses (0.5--20 mg/kg) of DEF produced ataxia, which progressed to paralysis and death in some birds. Large daily oral doses (40 and 80 mg/kg) caused a 'late acute' effect 4 days after administration. The clinical signs of the late acute effect were identical to those produced by n-butyl mercaptan (nBM), a hydrolytic product of DEF, and were not relieved by atropine sulfate. The late acute effect of DEF overlapped with the clinical signs of delayed neurotoxicity. These hens died early, and while one hen showed histopathological lesions in peripheral nerves, another showed unequivocal lesions in the central nervous system. Topical application of daily doses of DEF consistently produced delayed neurotoxicity in the absence of late acute poisonining and was characterized by degeneration of the central and peripheral nerve tissues. Orally administered DEF was rapidly metabolized in the gastrointestinal tract to nBM, which apparently caused the late acute toxic effect. Topically administered DEF, which was not subjected to gastrointestinal tract hydrolysis, caused delayed neurotoxicity but did not produce a late acute effect.
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PMID:Delayed neurotoxic, late acute and cholinergic effects of S,S,S-tributyl phosphorotrithioate (DEF): subchronic (90 days) administration in hens. 54 54

The chromatographic separation and biochemical characterization of a beta-bungarotoxin is described. This toxin is isolated as the most basic eluting protein of Bungarus multicinctus venom when separated by column chromatography on CM-Sephadex C-25. The protein migrated as a single band on pH 4.3 and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The molecular weight of this toxin was estimated to be 10 000 +/- 1000 by analytical sedimentation analysis. This value was consistent with the electrophoretic mobility of the toxin in SDS-polyacrylamide gels. The amino acid composition of this 11 000-dalton beta-bungarotoxin was similar to that of the 22 000-dalton beta-bungarotoxin previously reported (Lee et al. (1972) J. Chromatogr. 72, 71--82; Kelly, R.B. and Brown, III, F.R. (1974) J. Neurobiol. 5, 135--150; Kondo et al. (1978) J. Biochem. Tokyo 83, 91--99), suggesting that the 11 000-dalton toxin may be one of the polypeptide chains of the larger toxin. The 11 000-dalton beta-bungarotoxin was toxic to mice when injected intravenously. Animals that received lethal doses exhibited hyperexcitability followed by ataxia, convulsions, and death. The minimum lethal dose was 0.12 microgram/g body weight. This beta-bungarotoxin exhibited Ca2+-dependent phospholipase A activity comparable to that of the 22 000-dalton beta-bungarotoxin. The enzyme exhibited phospholipid substrate specificity in the rank order of phosphatidyl-choline, phosphatidylserine, phosphatidylethanolamine, and phosphatidyl-inositol. The enzyme activity was destroyed by boiling for 3 min at pH 8.6. In addition, an enzymatically inactive quantity of the 11 000-dalton toxin, equivalent to five times the minimum lethal dose of enzymatically active toxin, was not lethal when injected into mice. To test whether phospholipase A activity is responsible for lethality, bee venom phospholipase A2 was injected into mice at similar and greater concentrations with no toxic effect. Thus, while phospholipase A activity may be required for the lethal effect of the 11 000-dalton beta-bungarotoxin, the specificity of action of the toxin is not determined by its enzyme activity.
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PMID:Purification and biochemical characterization of an 11 000-dalton beta-bungarotoxin. 56

Calcium- and calmodulin-regulated protein phosphorylation has been suggested to play a role in the pathogenesis of organophosphorus compound-induced delayed neurotoxicity (OPIDN). This condition is characterized by ataxia that progresses to paralysis concurrent with a central-peripheral distal axonopathy after a delay period of 1-2 weeks following exposure to an organophosphorus compound causing delayed neurotoxicity, such as tri-o-cresyl phosphate (TOCP). Calcium/calmodulin (CaM) kinase II is involved in the increased phosphorylation of brain microtubule and spinal cord neurofilament triplet proteins following treatment of animals with organophosphorus compounds that are capable of producing OPIDN. In this study, chickens were given a single oral neurotoxic dose of 750 mg TOCP/kg body weight and killed after 1, 6, 14 or 21 days following treatment. Protein kinase-mediated phosphorylation of cytoskeletal proteins was studied in proximal and distal parts of sciatic nerves of control and treated hens. Peripheral nerve proteins were phosphorylated in vitro using [gamma-32P]ATP as a phosphoryl group donor. Phosphorylated proteins were separated by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein phosphorylation was detected by autoradiography and quantified by laser microdensitometry. The extent of Ca2+-calmodulin dependent phosphorylation of five cytoskeletal proteins was significantly increased in TOCP treated animals, particularly at 1 and 6 days after treatment, in both the proximal and distal portion of the nerve. The identity of these proteins was confirmed by 2-D PAGE as tubulin, the neurofilament triplet proteins and microtubule associated protein-2 (MAP-2). These results confirm earlier observation of the close temporal relationship between increased cytoskeletal protein phosphorylation and the development and OPIDN.
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PMID:Biochemical changes in sciatic nerve of hens treated with tri-o-cresyl phosphate: increased phosphorylation of cytoskeletal proteins. 133 13

Morphine releases endogenous opioids into the circulation of dogs. To test the stereospecificity of this effect, as well as to determine whether morphine also releases endogenous opioids centrally, which might be involved in its antinociceptive action, the effects of (-)-morphine sulfate (10 mg/kg, sc) or (+)-morphine hydrobromide on antinociception in a dog tail-flick test, on semi-quantified morphine-induced signs of salivation, emesis, defecation and ataxia, and on the plasma and cerebrospinal fluid (CSF) levels of endogenous opioid peptides were studied. Plasma and CSF levels of immunoreactive beta-endorphin (i-BE), met-enkephalin (i-ME), leu-enkephalin (i-LE), and dynorphin (i-DY) were quantified by radioimmunoassay in octadecylsilyl-silica cartridge extracts. Immunoreactive morphine (i-M) levels were measured in unextracted samples. (-)-Morphine treatment significantly increased antinociception, morphine-induced signs, i-M levels in plasma and CSF, and i-BE, i-ME, and i-LE levels in plasma, but not CSF. Levels of i-DY remained constant in plasma and CSF. (+)-Morphine treatment did not alter any of these parameters, indicating that the effects of morphine on nociception, behavioral signs, and plasma endogenous opioids in dogs were stereoselective. It is concluded that morphine does not cause an increase in immunoreactive endogenous opioid peptides in the CSF at the time of its peak antinociceptive effect.
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PMID:Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs. 167 91

Male Sprague-Dawley rats injected sc with a single sublethal dose of the organophosphate nerve agent, soman (100 micrograms/kg), had motor limbic seizures within 5-15 min. Pretreatment with a single dose of memantine HCl (MEM, 18 mg/kg, sc), alone or in combination with atropine sulfate (ATS, 16 mg/kg, sc), before soman prevented seizures without sedation or ataxia. Rats appeared normal or demonstrated increased exploratory activity. Excessive salivation, a peripheral manifestation of soman intoxication, was decreased by ATS, but pretreatment with ATS alone did not prevent seizures. After seizure onset, MEM +/- ATS, but not ATS, abolished seizures. Acetylcholinesterase (AChE) activity in several brain regions (cortex, stem, striatum, and hippocampus) was markedly reduced by soman, but not by MEM, ATS, or MEM + ATS. Preadministration of MEM + ATS in vivo significantly protected AChE from inhibition by soman. Memantine reduced inhibition of AChE activity in crude brain homogenates by soman, but not by edrophonium (anionic site inhibitor) or decamethonium (peripheral site inhibitor). Thus, MEM may bind to a different modulatory site, not yet characterized, to protect AChE. When given after onset of soman-induced seizures, treatment with MEM +/- ATS did not reactivate AChE although seizures were controlled, suggesting additional anticonvulsant mechanisms of action. At concentrations (10(-4) to 5 x 10(-4) M) which did not significantly alter the spontaneous firing of action potentials (APs), MEM limited sustained high frequency repetitive firing (SRF) induced by depolarization of spinal cord (mouse and rat) and neocortical (mouse) neurons in monolayer-dissociated cell culture. In the same range of concentrations, ATS both limited SRF and suppressed spontaneous activity, suggesting toxicity. In addition, MEM and ATS reversibly produced use-dependent block of depolarizing responses to acetylcholine (ACh) applied by pressure ejection to spinal cord neurons. Thus, the anticonvulsant efficacy of MEM, with or without ATS, may have resulted from a combination of actions, including protection of AChE from inhibition by soman, limitation of high frequency firing of APs, and blockade of excitatory postsynaptic responses to ACh.
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PMID:Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat. 173 53

In middle of Kii peninsula, one of the biggest mercury mine in Japan had been present until about 10 years ago. The mercury contents in water and fish are reported to be higher in this district. So we investigated the mercury in hair of patients and normal controls. In this study the subjects are 23 cases of ALS including 15 cases in Nara and Mie and 8 cases in other prefectures except in Kii peninsula, 14 cases with ataxia, 11 cases with other degenerative diseases like Parkinson's disease and Alzheimer's disease, 25 cases of cerebrovascular disease as compared to 26 normal controls. The hair are taken from 3 areas on head of patients and normal controls. They are washed in 2% sodium lauryl sulfate and stirred in distilled water several times, and they are soaked in acetone and dried in filter paper. They are inserted in fire and vaporized mercury are measured (Zeeman Effect Mercury Analyzer) in ppm. The hair mercury concentration is 2.81 ppm in ALS in total, 3.62 ppm in ALS in Nara and Mie and 1.39 ppm in outside of Kii Peninsula, 2.34 ppm in ataxia, 1.83 ppm in other degenerative diseases, 1.66 ppm in cerebrovascular disease and 1.44 ppm in normal controls. Statistically it is significant (p less than 0.05) between that in ALS in Nara and Mie and that in normal controls. 6 cases (40%) with ALS in Nara and Mie have the value above the mean +2 standard deviation of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mercury in hair of patients with ALS]. 280 5

Forty-eight newly captured free-ranging feral stallions (Equus caballus) from two different locations and six captive stallions were immobilized using combinations of etorphine hydrochloride, xylazine hydrochloride and atropine sulfate with or without acepromazine. Six animals were immobilized twice, 1 mo apart. The drugs were administered either intramuscularly (n = 13) or intravenously (n = 44). Mean immobilization time (+/- SE) after intravenous (i.v.) injection of etorphine, xylazine and atropine was 55 +/- 4 sec (range 20 to 185 sec) compared to 708 +/- 131 sec (range 390 to 1,140 sec) for intramuscular (i.m.) injection. Immobilization was reversed with i.v. administration of 3 to 11 mg diprenorphine hydrochloride and 16 to 24 mg yohimbine hydrochloride. Average time from administration to standing and walking was 86 +/- 7 sec (n = 55). Reversal of etorphine-induced immobilization with an amount of diprenorphine equal to the etorphine and administered i.v. was as effective as a 2:1 ratio of diprenorphine to etorphine. Acepromazine had no effect on induction time, but decreased relaxation after immobilization and prolonged ataxia after reversal of the etorphine and xylazine. Eight free-ranging horses were immobilized in 708 +/- 132 sec by darting with 5.5 mg etorphine, 1,300 mg xylazine and 15 mg atropine from a helicopter. Three animals died during the study: one immediately after reversal of an i.v. administration, one from a broken neck during induction from darting, and one was found a week later at the site of darting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid reversible immobilization of feral stallions using etorphine hydrochloride, xylazine hydrochloride and atropine sulfate. 362 9

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.
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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.
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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


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