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)

General pharmacological effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY), a new antiproteolytic agent, were studied and the following results were obtained. Acute administration of large doses of FOY in conscious dogs and rabbits caused a decrease in spontaneous motility, ataxia, cyanosis, collapse, mydriasis, and respiratory paralysis. The agent had no effect on the central nervous system and exhibited hypotensive effects in dogs in doses of more than 1 mg/kg. Hypotensive responses were not inhibited by treatment with atropine or hexamethonium. FOY had no effects on ECG in the rabbit at doses of less than 30 mg/kg and at doses from 10(-6) to 10(-4)g/ml, distinctly reduced the amplitude of the spontaneous and rhythmic contractions of the isolated rabbit ileum, guinea-pig ileum and rat uterus preparation. The contractile response to nerve stimulation, noradrenaline and barium was suppressed in isolated guinea-pig vas deferens. FOY had no effects on the twitch response of gastrocnemius muscle to sciatic nerve stimulation in rats. The drug caused local irritant effects in rabbits and rats.
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PMID:[Pharmacological action of [ethyl p(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY)]. 23 87

The cases of two sisters with abetalipoproteinemia are reported. Both presented the complete clinical and biological features of the disease: ataxia, retinitis pigmentosa, lack of apolipoprotein B, chylomicrons, LDL and VLDL, reduced titers of serum cholesterol and triglycerides, acanthocytosis, very low levels of serum vitamin A and E. Abetalipoproteinemia is a rare autosomal inherited disease. It is usually revealed during early childhood by steatorrhea and failure to thrive; ataxia and retinitis pigmentosa appear later. The originality of these two cases stems from: 1) their late and fortuitous diagnosis: the first sister was investigated at the age of 42 after the discovery of a vitamin K induced coagulation disorder. The other sister was 39 when she was routinely examined as a family member; 2) the presence of constipation without any other suggestive digestive complaint. However, white discoloration of the duodenal mucosa seen at endoscopy and lipid droplets within the intestinal absorptive cells at biopsy were characteristic. Barium studies showed diffuse involvement of the small bowel which was displaced by an enlarged sigmoid. Treatment consists of administration of vitamin A and vitamin E which prevent or delay ocular and neurologic symptoms. Vitamin K is associated whenever necessary.
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PMID:[Abetalipoproteinemia. Apropos of 2 cases]. 369 94

Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.
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PMID:Polysorbate 80: a pharmacological study. 402 3

In the present study the general pharmacological properties of ethyl-N-[2-amino-6-(4-fluor-phenylmethylamino)pyridin-3-yl]carbama te (flupirtine, D 9998), a structural new analgesic, are described. In several tests with mice flupirtine shows a centrally depressant component of action. However, regarding undesirable side effects as ataxia, inhibition of motor activity etc. this action is, with respect to the analgesic effective doses less pronounced than those of comparable analgesics, for instance phenacetin. In relatively low doses flupirtine antagonizes tremor induced by oxotremorine in mice. This activity is probably not caused by a central anticholinergic action, because other anticholinergic effects have not been observed. It should be pointed out that flupirtine antagonizes the morphine-induced tail phenomenon in mice in relatively low doses. This action obviously differentiates flupirtine from opiates. Up to high doses flupirtine does not cause catalepsia in mice, consequently its centrally depressant activity does not resemble that of reserpine and also is not comparable with those of neuroleptic agents. The corneal and pinnal reflexes are not influenced by flupirtine and the righting reflex is slightly delayed in high doses. The anticonvulsive activity of flupirtine observed in the pentetrazol shock test (mouse) after high doses probably cannot be considered to occur within the analgesic dose range. Inhibition of amphetamine toxicity in mice observed in doses near the hypnotic doses may be caused by non-specific effects. In vitro tests with isolated trachea or ileum of guinea pigs show that flupirtine possesses no or very weak antagonism against histamine-induced spasms. In spasms caused by barium chloride flupirtine shows a weak musculotropic-spasmolytic activity. Investigations on the circulatory system of dogs do not indicate any incompatibilities with flupirtine. No evidence of antiarrhythmic activity was found in rats. Flupirtine has no local anesthetic activity in mice but some weak effects on the cornea of rabbits. Like several other analgesics flupirtine shows in rats a reversible antidiuretic action including sodium and chloride retention which is of relatively short duration and is not observed in long-term studies in rats and dogs. In contrast to many stronger antiinflammatory compounds, flupirtine does not possess ulcerogenic activity in rats up to high doses. A minimal inhibition of intestinal motility (mouse) is observed only in doses higher than the analgesic effective doses.
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PMID:[General pharmacologic studies on the analgesic flupirtine]. 403 52

An unusual case of right posterior brainstem infarction with isolated deficits of severe dysphagia and ataxia is presented. Neurological examination revealed dysfunction of the pharyngeal and laryngeal branches of cranial nerves IX, X, and a paralyzed right vocal cord. The patient was unable to swallow 1/4 teaspoon of applesauce. Modified barium swallow revealed extremely sluggish pharyngeal peristalsis and absent swallowing reflex. Percutaneous esophageal gastrostomy tube was inserted and an intensive dysphagia rehabilitation program was initiated. Pharyngeal-phase-oriented protocol was used. Results were significantly improved compensatory pharyngeal and laryngeal function with restoration of swallowing and no aspiration. This case illustrates successful management of dysphagia associated with brainstem infarction and the benefits of a coordinated multidisciplinary protocol.
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PMID:Brainstem infarct with pharyngeal dysmotility and paralyzed vocal cord: management with a multidisciplinary approach. 843 Nov 8

The oral, pharyngeal, and esophageal stages of swallowing were evaluated in 8 patients with recessively or dominantly inherited pure sensory ataxia. Six patients had swallowing difficulties: solid bolus obstruction, coughs during eating, and choking episodes. One patient had chronic bronchitis and another had recurrent pneumonia. The patients underwent a biphasic radiological barium swallow, including videofluoroscopy. No patient had a completely normal swallow. All had normal oral function, whereas pharyngeal function was abnormal in 6 patients. Esophageal function was abnormal in 6 patients. The swallowing dysfunction did not correlate with the severity of motor or sensory dysfunction in the limbs, nor with age or duration of ataxia. Our study shows that swallowing dysfunction is common in hereditary sensory ataxia. This dysfunction is likely to be due to involvement of the nucleus of the solitary tract in the brainstem. Despite some of the patients having suffered from choking episodes and others from bronchopulmonary complications, they did not spontaneously admit dysphagia. Swallowing should be evaluated thoroughly in patients with hereditary sensory ataxia since dysphagia in these patients might bring serious and potentially fatal complications.
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PMID:Swallowing in hereditary sensory ataxia. 872 Oct 73

We have investigated the functional consequences of three P/Q-type Ca(2+) channel alpha1A (Ca(v)2.1alpha(1)) subunit mutations associated with different forms of ataxia (episodic ataxia type 2 (EA-2), R1279Stop, AY1593/1594D; progressive ataxia (PA), G293R). Mutations were introduced into human alpha1A cDNA and heterologously expressed in Xenopus oocytes or tsA-201 cells (with alpha(2)delta and beta1a) for electrophysiological and biochemical analysis. G293R reduced current density in both expression systems without changing single channel conductance. R1279Stop and AY1593/1594D protein were expressed in tsA-201 cells but failed to yield inward barium currents (I(Ba)). However, AY1593/1594D mediated I(Ba) when expressed in oocytes. G293R and AY1593/1594D shifted the current-voltage relationship to more positive potentials and enhanced inactivation during depolarizing pulses (3 s) and pulse trains (100 ms, 1 Hz). Mutation AY1593/1594D also slowed recovery from inactivation. Single channel recordings revealed a change in fast channel gating for G293R evident as a decrease in the mean open time. Our data support the hypothesis that a pronounced loss of P/Q-type Ca(2+) channel function underlies the pathophysiology of EA-2 and PA. In contrast to other EA-2 mutations, AY1593/1594D and G293R form at least partially functional channels.
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PMID:Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. 1174 3

Regulation of gene expression by tissue-specific transcription factors involves both turning on and turning off transcription of target genes. Runx3, a runt-domain transcription factor, regulates cell-intrinsic functions by activating and repressing gene expression in sensory neurons, dendritic cells (DC), and T cells. To investigate the mechanism of Runx3-mediated repression in an in vivo context, we generated mice expressing a mutant Runx3 lacking the C-terminal VWRPY, a motif required for Runx3 interaction with the corepressor Groucho/transducin-like Enhancer-of-split (TLE). In contrast with Runx3(-/-) mice, which displayed ataxia due to the death of dorsal root ganglia TrkC neurons, Runx3(VWRPY-/-) mice were not ataxic and had intact dorsal root ganglia neurons, indicating that ability of Runx3 to tether Groucho/TLE is not essential for neurogenesis. In the DC compartment, the mutant protein Runx3(VWRPY-) promoted normally developed skin Langerhans cells but failed to restrain DC spontaneous maturation, indicating that this latter process involves Runx3-mediated repression through recruitment of Groucho/TLE. Moreover, in CD8(+) thymocytes, Runx3(VWRPY-) up-regulated alphaE/CD103-like WT Runx3, whereas unlike wild type, it failed to repress alphaE/CD103 in CD8(+) splenocytes. Thus, in CD8-lineage T cells, Runx3 regulates alphaE/CD103 in opposing regulatory modes and recruits Groucho/TLE to facilitate the transition from activation to repression. Runx3(VWRPY-) also failed to mediate the epigenetic silencing of CD4 gene in CD8(+) T cells, but normally regulated other pan-CD8(+) T cell genes. These data provide evidence for the requirement of Groucho/TLE for Runx3-mediated epigenetic silencing of CD4 and pertain to the mechanism through which other Runx3-regulated genes are epigenetically silenced.
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PMID:Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3. 1665 17

Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking. In association with prominent Purkinje neuron atrophy, repetitive spiking is restored, although at a greatly reduced firing frequency. In spite of a continued impairment in spike repolarization and a persistently reduced BK channel mediated afterhyperpolarization (AHP), repetitive spiking is maintained, through the increased activity of barium-sensitive potassium channels, most consistent with inwardly rectifying potassium (Kir) channels. Increased activity of Kir channels results in the generation of a novel AHP not seen in wild-type Purkinje neurons that also accounts for the reduced firing frequency late in disease. Homeostatic changes in Purkinje neuron morphology that help to preserve repetitive spiking can also therefore have deleterious consequences for spike frequency. These results suggest that the basis for spiking abnormalities in SCA2 differ depending on disease stage, and interventions targeted towards correcting potassium channel dysfunction in ataxia need to be tailored to the specific stage in the degenerative process.
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PMID:Potassium channel dysfunction underlies Purkinje neuron spiking abnormalities in spinocerebellar ataxia type 2. 2901 52

We present a case of Sandifer syndrome in a 3-year-old girl who initially presented with a history of recurrent paroxysmal head drops associated with ataxia-like symptoms and recurrent falls sustaining a clavicular fracture on one occasion. She was referred to and seen by the paediatric neurologist. Physical examination, electroencephalogram, MRI brain, electromyograph single fibre study and blood tests were all normal. With the history of hiccups and choking-like episodes she was referred to the speech and language therapist (SALT). SALT assessment did not reveal indications of swallowing impairment or possible aspiration. A barium swallow later showed small amount of reflux into the distal oesophagus. This prompted a trial of lansoprazole and she was referral to the gastroenterologists. Endoscopy and oesophageal manometry were essentially normal. However, the pH impedance study revealed severe gastro-oesophageal reflux disease. She continued with lansoprazole and dairy-free diet and her symptoms resolved.
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PMID:Paroxysmal head drops with ataxia-like symptoms presenting as Sandifer syndrome in a 3-year old girl. 3213 46


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