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)

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

The effects of administration of a commercially available extract of Gingko biloba (EGB) on bromethalin-induced brain lipid peroxidation and cerebral edema in adult male Sprague-Dawley rats was determined. Gingko biloba extract was given (100 mg/kg) by gavage immediately after bromethalin (1.0 mg/kg) administration. Rats were euthanatized at 24 hours after dosing. Brain lipid peroxidation was determined by measurement of brain malonaldehyde-thiobarbituric acid chromophore (MDA-TBA) concentration, brain sodium concentration, and brain water content. Treatment of bromethalin-dosed rats (10/group) with EGB was associated with a statistically significant (P less than 0.05) decrease in clinical sign severity, compared with bromethalin-dosed saline solution-treated rats. All rats given bromethalin and saline solution developed clinical signs of toxicosis including CNS depression, hind limb weakness, ataxia, paralysis, and coma. Some rats given bromethalin and EGB developed clinical signs, however, none developed hind limb paralysis. The brain MDA-TBA concentration (2.4 +/- 0.5 delta MDA-TBA concentration/mg of protein), percentage of water in brain tissue (80.3 +/- 0.30%), and brain sodium concentration (6.68 +/- 0.21 mg/g of dry weight) were significantly increased in rats given bromethalin and saline solution, compared with control rats given saline solution (1.0 +/- 0.1 delta MDA-TBA concentration/mg of protein; 78.1 +/- 0.33% water in brain tissue; 4.83 +/- 0.30 mg of brain Na+/g of dry weight) and rats given bromethalin and EGB (1.6 +/- 0.2 delta MDA-TBA concentration/mg of protein; 79.3 +/- 0.31% water in brain tissue; 5.37 +/- 0.34 mg of brain Na+/g of dry weight).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of an extract of Gingko biloba on bromethalin-induced cerebral lipid peroxidation and edema in rats. 153 6

Natural pyrethrin and synthetic pyrethroid insecticides have been considered among the safest classes of insecticides available. Pyrethrins and pyrethroids are classified on the basis of their chemical structures and their toxicologic, neurophysiologic and pharmacologic effects. Cellular effects of pyrethrin and pyrethroid insecticides have been postulated to involve interactions with sodium channels, receptor-ionophore complexes, neurotransmitters, and ATPases. Toxicity is a function of chemical structure, metabolism, route of exposure, and the presence or absence of synergists. Pyrethroid insecticides are neurotoxic, and the development and severity of clinical signs is proportional to the nervous tissue pyrethroid concentration. Type I pyrethroid poisoning in mice and rats produces a syndrome characterized by tremors, prostration and altered startle reflexes. Type II pyrethroid poisoning in mice and rats causes ataxia, convulsions, hyperactivity, choreoathetosis and profuse salivation. A presumptive diagnosis of pyrethrin/pyrethroid poisoning is based upon history of exposure, development of appropriate clinical signs, and chemical analysis for insecticide residues. Treatment of pyrethrin and pyrethroid toxicosis involves basic life support, seizure control when needed, and the prevention of further insecticide absorption.
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PMID:Neurotoxicology of pyrethrin and the pyrethroid insecticides. 171 67

Effects of administration of triflupromazine were evaluated in 11 adult domesticated camels (Camelus dromedarius) weighing 403 +/- 29.5 kg (Mean +/- SE). Six camels were used to evaluate sedative properties of the drug and its effects on haematological and blood biochemical parameters. In the remaining 5 camels, effects on haemodynamics, acid base status and blood gases were studied. In all the animals triflupromazine was administered intramuscularly in the gluteal region at the rate of 2 mg/kg. Camels voluntarily sat down 48.9 +/- 5.4 min after administration of the drug but stood up again if disturbed. Drowsiness, drooping of lower lip and salivation were evident. The animals stood on their own and started walking with ataxia after 159 +/- 7 min and recovered completely from the effect of drug within 259 +/- 23 min. The drug caused a significant tachycardia and a moderate hypotension. The decrease in central venous pressure was also significant. Rectal temperature, respiratory rate, acid base status, blood gases, haemoglobin concentration, packed cell volume, total erythrocyte count, total leucocyte count, differential leukocyte count, blood urea nitrogen, plasma alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, blood glucose and plasma concentrations of sodium, potassium, chloride and inorganic phosphate were not significantly affected by triflupromazine.
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PMID:Evaluation of triflupromazine as a sedative in camels (Camelus dromedarius). 177 79

Intramuscular (i.m.) and intravenous (i.v.) administration of detomidine at doses of 10, 20 and 40 micrograms/kg body mass was evaluated for its sedative and analgesic properties in 15 goats (Capra hircus). The drug produced dose- and route-dependent sedation. The 10 micrograms/kg dose was effective only when administered i.v. There was no observable analgesia at this dose. Higher doses produced effective sedation and moderate analgesia of the body with either route of administration. Severe ataxia and sternal recumbency were seen in all the animals after the dose of 40 micrograms/kg. Other effects of detomidine in these goats included mild to moderate salivation, depressed respiratory rate, decreased rectal temperature, bradycardia and hyperglycaemia. Plasma concentrations of total protein, sodium, potassium and chloride were not affected.
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PMID:Evaluation of detomidine as a sedative in goats. 178 30

A series of 3-oxo-5-substituted-benzylidene-6-methyl-(4H)-2- pyridazinylacetamides and 2-pyridazinylacetylhydrazides were synthesized and evaluated for anticonvulsant activity against electrically and chemically induced seizures. In the maximal electroshock-induced seizures test, most of the derivatives showed an anticonvulsant effect better than that of sodium valproate, a commonly used anticonvulsant drug. At 100 mg/kg orally, compounds 5a and 5b respectively protected 50 and 60% of the mice against pentylentetrazole-induced seizures. In addition, these two derivatives showed significant anticonvulsant properties at doses that did not produce ataxia or sedation. The title compounds were also tested for their ability to antagonize convulsions induced by bicuculline and strychnine. Their effect on tremors induced by oxotremorine in mice was also evaluated.
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PMID:Anticonvulsant activity of 3-oxo-5-substituted benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-pyridazinylacetylhydrazides. 212 24

To assess the effects of moderate exercise [40-70% maximal oxygen uptake (VO2max)] on resting blood pressures, the presence of cerebrovascular lesions, and the life spans of stroke-prone hypertensive rats, nontrained and trained male and female rats were assigned to two experimental groups. The first (n = 48) were exercise trained after 38 days of age, whereas the second (n = 44) initiated exercise training when the animals were 134 days of age. To facilitate cerebrovascular lesions, the sodium concentrations in the rat chow and in the drinking solutions were increased. Symptoms utilized to denote the presence of cerebrovascular lesions were irritability, hyperresponsiveness, ataxia, lethargy, unwillingness to run, and combinations thereof. All brains were removed immediately after death, fixed, and evaluated grossly and microscopically for lesions. In the study with the younger animals, training was associated with a 7-9% increase in VO2max that was statistically significant only in animals with no histological evidence of cerebrovascular lesions. For the older animals, a significant 5-8% increase in VO2max was noted for animals with or without lesions. After 42 days of training for both groups, resting blood pressures for the trained groups with histological lesions were significantly lower. However, this trend did not continue, and the older trained rats appeared to have strokes earlier and to die sooner than their nontrained controls. Although 83% of the older animals had subjective evidence for a stroke before they died, the percentage of animals with lesions ranged from 42 to 58%, with the trained groups having higher percentages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exercise training and incidence of cerebrovascular lesions in stroke-prone spontaneously hypertensive rats. 234 35

Amygdala-kindled rats were treated with valproic acid (VPA; administered as its sodium salt) 3 times daily at 200 mg/kg i.p. for 6 weeks, and anticonvulsant and adverse effects during this period were studied. Groups of nonkindled rats were treated in parallel for determination of VPA and its major active metabolites in various brain regions after different durations of treatment. After the first injection of VPA, 200 mg/kg, seizure severity, seizure duration and duration of electrical afterdischarges recorded from the stimulated amygdala were reduced significantly, but only one of nine animals was protected completely from kindled seizures. At day 3 of chronic treatment, the anticonvulsant activity of VPA had increased markedly so that seven of nine animals were totally protected from seizures. However, this potent anticonvulsant effect was only transitory so that after 1 week of treatment the anticonvulsant effect of the medication was similar to that obtained after the first dosing. The effect of VPA remained at this level for the subsequent weeks, but there was a second, more permanent increase in the number of protected animals after 4 to 6 weeks. Plasma and brain levels of VPA and its metabolites remained relatively constant throughout the chronic treatment although there was a moderate accumulation of some metabolites, e.g., trans isomer of 2-propyl-2-pentenoic acid, in specific brain nuclei. The most prominent adverse effects of VPA were ataxia, muscle relaxation, wet-dog shake behavior and an increase in body temperature. Except for body temperature, tolerance developed to these adverse effects, but escape from wet-dog shake behavior occurred much more rapidly than reduction of other adverse effects. Pathohistological examination of liver sections from animals treated with VPA for 6 weeks showed no indication of any hepatotoxic effects. After drug withdrawal, kindled seizure parameters returned toward control values without evidence of significant carry-over effects. Five days after termination of treatment, only minute amounts of VPA and trans isomer of 2-propyl-2-pentenoic acid were determined in some brain regions, indicating that there was no persistence of active drug or metabolite concentrations in the brain.
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PMID:Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment. 250 34

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its effect on the central nervous system (CNS) was studied. 1. When orally administered in mice, beraprost sodium at 0.3 mg/kg caused a flush of skin, a suppression of spontaneous motility, and a fall of body temperature. At 1 mg/kg and more, it showed obvious sedation, prolongation of hexobarbital hypnosis, and analgesic action in acetic acid-induced writhing test. However, even at 3 mg/kg beraprost sodium neither induced ataxia nor had anticonvulsant activity. Hypothermia was also observed in rabbits at 1 mg/kg (p.o. and i.v.). 2. When intravenously administered, beraprost sodium exerted long-lasting action on the CNS, while its pharmacological effects resembled those of PGI2. 3. Oral administration of beraprost sodium did not inhibit aggregation toxicity induced by methamphetamine (20 mg/kg i.p.) in mice. Beraprost sodium at doses higher than 1 mg/kg enhanced aggregation toxicity induced by methamphetamine (5 mg/kg i.p.), while intracerebral ventricular administration of beraprost sodium failed to enhance it. 4. In rat spinal reflex, intravenous administration of beraprost sodium (0.1 mg/kg) slightly enhanced monosynaptic reflex and at a high dose (1 mg/kg) suppressed polysynaptic reflex. 5. In the rabbit EEG, intravenous administration of beraprost sodium at a high dose (1 mg/kg) showed some effects such as the continuous pattern of wakefulness and a fall in power of the EEG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:General pharmacology of beraprost sodium. 1st communication: effect on the central nervous system. 251 Jul 42

Three groups of 5 pigs each were fed a high selenium (Se) diet by mixing either Astragalus praelongus (31.6 ppm Se in feed), A bisulcatus (31.7 ppm Se in feed), or sodium selenate (26.6 ppm Se in feed) with commercial hog feed. Ten control pigs were fed only commercial hog chow containing trace selenium (0.44 ppm Se). Pigs were fed for 9 weeks and necropsied when they had ataxia or paralysis. Blood was collected for hematologic and serum biochemical determinations, and samples of various tissues were collected and fixed in neutral-buffered 10% formalin for histologic evaluation or frozen for determination of selenium concentration. All forms of selenium induced clinical signs of weight and hair loss, with cracked hooves and inflamed coronary bands developing in all Na2SeO4-fed pigs and 1 A praelongus-fed pig, but not in A bisulcatus-fed pigs. Serum calcium, phosphorus, and albumin concentrations were unchanged or significantly decreased from prefeeding values in groups fed selenium. Serum aspartate transaminase (AST) activities in Astragalus species-fed groups, and amylase activities and PCV in all groups of pigs fed selenium, were increased. Serum alkaline phosphatase and creatine kinase activities were significantly increased in the A praelongus-fed pigs and significantly decreased in Na2SeO4-fed pigs. Terminal tissue and body fluid selenium concentrations were determined in all groups of pigs fed selenium and compared with values in control pigs. Urine and bile concentrations were increased by the greatest factor (40 to 100x), with tissue concentrations of selenium increased by a lesser factor (6 to 17x).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicosis in pigs fed selenium-accumulating Astragalus plant species or sodium selenate. 278 23


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