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)

Cisapride is an oral prokinetic agent used to facilitate or restore motility in the gastrointestinal tract. The National Animal Control Center has received 17 reports of accidental overexposure of dogs to cisapride since 1994. Doses of 640 mg/kg in dogs were reported to be lethal, but severe clinical signs have been noted at acute exposures as low as 18 mg/kg. The most common signs include diarrhea, muscle tremors and fasciculations, ataxia and incoordination, and hyperthermia. Available treatment is symptomatic and supportive. Activated charcoal is effective in reducing plasma cisapride levels.
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PMID:Cisapride toxicosis in dogs. 869 86

1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.
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PMID:Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice. 873 Jul 57

It is often difficult to estimate slight alterations in the severity of ataxia by bed-side neurological examinations. We analyzed the heel-knee tapping test, which has often been used as a standard bed-side examination to check incoordination in lower limbs, using a new motion measurement system "video/computer motion measurement system". We studied 9 normal controls and 21 patients with spinocerebellar degenerations (SCD). In patients with SCD, the up-and-down motion range of the heel was variable and the heel moved in the anterior-and-posterior direction, because of knee sways during the test. Following oral administration of TRH analogue, TA-0910, above-mentioned findings were clearly improved. Analysis of spatial and time elements of the knee joint demonstrated quantitative improvement. Therefore, an effect of TA-0910 on incoordination of the lower limbs could be proved objectively by a computer motion measurement system.
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PMID:[A study of heel-knee tapping test in cerebellar ataxia by a motion measurement system]. 877 95

The effects of intravenous administration of variable-dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (< 2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly greater proportion of cats which received ketamine and midazolam 0.5 mg/kg or above did not swallow in response to a finger or a laryngoscope placed in the mouth compared with that which received ketamine alone. The length of time in which cats did not swallow was only significantly longer at midazolam doses of 1.0 mg/kg and above. At midazolam doses of 0.5 mg/kg or above, the proportion of cats without a nociceptive response to a tail or paw clamp was significantly greater than cats which received ketamine alone. The time period without nociceptive response, however, was not influenced by midazolam administration. The time taken for cats which received ketamine and midazolam 0.05 mg/kg or 0.5 mg/kg to assume sternal position, walk with ataxia, walk without ataxia, behave normally when approached or restrained and recover normal arousal state was not significantly different from cats which received ketamine alone. Ketamine and midazolam 5.0 mg/kg significantly prolonged all recovery times compared with ketamine alone. Unfortunately, a greater proportion of cats which received ketamine and midazolam 0.5 or 5.0 mg/kg exhibited detrimental behavioural effects. These were more likely to be adverse and included restlessness, vocalization and difficulty approaching and restraining cats. In this study, an effect of sex of the cats was found, with male cats taking a significantly longer to recover to sternal recumbency and walk with ataxia, while female cats took longer to recover to a normal arousal state.
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PMID:The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats. 880 80

Studies with inbred strains of mice have suggested that there may be a genetic correlation between strain sensitivities to the ataxic and hypothermic responses to ethanol (EtOH), which would suggest that some genes influence both responses. To test this hypothesis, EtOH sensitivity was determined in replicate lines of mice selectively bred for sensitivity (COLD) or resistance (HOT) to acute ethanol hypothermia. Several tests were used to index ataxia, related traits such as muscle strength, and locomotor activity. The screen test yielded a dose-dependent EtOH-induced decrease in performance that did not differ between the selected lines. Based on the dose-response characteristics of this task, 2.5 g/kg of EtOH was used as the test dose for the remaining experiments. Results from the fixed-speed rotarod and the grid test of motor incoordination also indicated no significant differences between HOT and COLD mice in sensitivity to EtOH impairment. When the selected lines were tested on an accelerating rotarod, COLD mice were impaired by the acute EtOH injection, but HOT mice were unaffected. COLD mice were more sensitive to EtOH-induced decrements in grip strength and locomotor activity. Overall, the results indicated that HOT and COLD mice were only differentially sensitive to EtOH in some tasks related to ataxia, suggesting that some genes must be associated uniquely with EtOH-induced hypothermia or ataxia. The mixed results from the various tests indicate that ataxia can best be conceived as a group of related complex behaviors that cannot be assessed adequately by the use of a single task and that ataxia-related behaviors are influenced by different groups of genes.
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PMID:Sensitivity to ethanol-induced ataxia in HOT and COLD selected lines of mice. 898 11

We report a case of sporadic olivopontocerebellar atrophy (OPCA) with marked laterality of cerebellar atrophy and degenerative changes in the corticopontine tract. A 35-year-old man was admitted to our hospital for evaluation of titubation, gait disturbance, dysarthria, and urinary and fecal incontinence. Neurological examination showed a wide based gait, slurred speech, truncal ataxia, slightly saccadic ocular movement, and finger-to-nose incoordination, greater on the right than the left. Deep tendon reflexes were hyperactive and preserved with the right side greater than the left. Bilateral Babinski signs were present, and the patient had neurogenic bladder without orthostatic hypotension. Cranial MRI showed atrophy of the cerebellum with right dominance and of the pons. On T2- and PD-weighted images, high-intensity areas were detected at the left internal capsule, crus cerebri and ventral pons. These findings were compatible with the right dominance of the clinical symptoms. The high intensity area detected at the posterior internal capsule was more extensive than that seen in patients with motor neuron disease. This finding may coincide with the degenerative changes in the corticopontine tract. Moreover, 99mTc-HMPAO-SPECT showed the crossed cerebello-cerebral diaschisis (CCCD) pattern, which indicates the decreased CBF in the right cerebellar hemisphere and the left frontal lobe. These findings may reflect degenerative changes in the corticopontine tract in OPCA.
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PMID:[Neuroradiological findings of sporadic olivopontocerebellar atrophy with marked laterality and degenerative changes in the corticopontine tract]. 899 39

As an extension of our previous work pertaining to brain adenosinergic modulation of ethanol-induced motor incoordination, the effect of direct intracerebellar administration of the A1-selective adenosine agonist, N6-cyclohexyladenosine (CHA) on ethanol-induced motor incoordination was evaluated. Marked accentuation of ethanol-induced motor impairment by CHA was observed. No change in the normal motor coordination was noted when CHA administration was followed by saline instead of ethanol. Intracerebellar cAMP or its analog, 8-(4-chlorophenylthio)-cAMP, significantly inhibited ethanol's motor impairment in a dose-related manner as well as abolished CHA's accentuating effect on ethanol-induced motor incoordination. These observations suggested a possible involvement of cAMP in the adenosinergic modulation and in the expression of ethanol-induced motor incoordination. Further support was provided by the observation of a marked accentuation and attenuation in a dose-related manner of ethanol-induced motor impairment as well as CHA's accentuation of ethanol's motor impairment by intracerebellar miconazole and forskolin, respectively. However, equimolar intracerebellar doses of miconazole and forskolin (inhibitor and stimulator of adenylyl cyclase, respectively) failed to significantly alter ethanol-induced motor incoordination probably due to their mutual functional antagonism. The expression of adenosinergic modulation and that of ethanol-induced motor impairment most likely involved Gi protein-coupled receptor(s) (such as adenosine receptors). The involvement of receptors linked to pertussis toxin-sensitive G-proteins was suggested because intracerebellar pertussis toxin pretreatment markedly inhibited ethanol-induced motor incoordination as well as CHA's accentuation of ethanol's motor impairment. Finally, cAMP, unlike its antagonism to CHA's accentuation, failed to antagonize the accentuation of ethanol-induced motor impairment by intracerebellar GABA(A) agonist (+)-muscimol. This indicated selectivity of cAMP participation in G protein coupled receptor (such as adenosine)-mediated response and not in ionic channel coupled receptor (such as GABA(A))-mediated mechanism. Overall, the data suggested a possible involvement of cerebellar adenylyl cyclase-cAMP signalling pathway in the adenosinergic modulation of ethanol's ataxia.
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PMID:Mouse cerebellar adenosinergic modulation of ethanol-induced motor incoordination: possible involvement of cAMP. 913 26

Ataxia, or incoordination of movement, is a disorder that can be caused by damage to several different nervous system structures. Common causes of ataxia include damage of the cerebellum and damage of sensory structures. Sensory ataxia is distinguishable from cerebellar ataxia, because the sensory ataxia causes symptoms to worsen when movements are made with the eyes closed. The basic mechanism underlying ataxia is not yet understood, although studies indicate that ataxia may be due in part to an inability to coordinate the relative activity of multiple muscles and adjust movements at a given joint for the effects of other moving joints (interaction torques). Based on these findings, it could be reasoned that treatments focusing on strategies to reduce the complexity of a movement by minimizing the number of moving joints or by stabilizing against the inertial effects of limb movement will improve function. 2,12-14,21-23 Further testing of treatments for ataxia, however, is needed. Ataxia may be best treated by teaching people to avoid rapid multijoint movements and instead make slower movements limited to single joints.
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PMID:Mechanisms of ataxia. 932 25

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract. Work presented here describes the behavioral and neuropathological course seen in mutant SCA1 transgenic mice. Behavioral tests indicate that at 5 weeks of age mutant mice have an impaired performance on the rotating rod in the absence of deficits in balance and coordination. In contrast, these mutant SCA1 mice have an increased initial exploratory behavior. Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has divergent effects on the motor behavior of juvenile animals: a compromise of rotating rod performance and a simultaneous enhancement of initial exploratory activity. With age, these animals develop incoordination with concomitant progressive Purkinje neuron dendritic and somatic atrophy but relatively little cell loss. Therefore, the eventual development of ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but the result of cellular dysfunction and morphological alterations that occur before neuronal demise.
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PMID:Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations. 929 84

A 70-year-old woman who has been suffering from diabetes mellitus since 67 years of age rapidly developed severe truncal ataxia. Neurological examination showed severe truncal ataxia, incoordination and decreased deep sensations in the bilateral lower extremities. A CSF study revealed a moderately elevated total protein (125 mg/dl) without any elevation of the cell count. A nerve conduction study supported the diagnosis of polyneuropathy. Lumbar MRI revealed spinal canal stenosis at the L3/L4-L5/S1 intervertebral levels due to disk herniations and ossification of the yellow ligaments. We examined cerebellar stimulation in order to determine whether the ataxia was due to dysfunction of the cerebellum or peripheral nervous system. Conditioning electrical stimulation over the cerebellum did not change the size of motor potentials evoked by magnetic cortical stimulation in the right first dorsal interosseous muscle. Her clinical course was good, and the limb and truncal ataxia became very mild about 4 months after the onset, although there was little change in the decreased deep sensations. The cerebellar stimulation in the second study was normal. We diagnosed her as having acute cerebellar ataxia and thought that the decreased deep sensations were due to diabetic polyneuropathy and lumbosacral radiculopathies. A cerebellar stimulation study was useful for the diagnosis and follow-up evaluation of acute cerebellar ataxia in this patient.
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PMID:[The diagnosis and follow-up evaluation of acute cerebellar ataxia supported by a cerebellar stimulation study]. 949 Sep 7


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