Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intramuscular neutrolysis with phenol has been used for 10 years in the management of spasticity in children. Best results depend on fastidious technique and realistic use of the procedure. Sedation or anesthesia was used in all cases -- 5% phenol in water was used for all procedures. The main indications were spasticity which interfered with function, either actual or potential, or with care. Where uninhibited vestibular or tonic neck reflexes affect muscle tone, or there is dystonia or athetosis, the procedure is less effective than where spasticity alone is present. Duration of relief of spasticity ranged from 1 month to more than 2 years. About one half of the lower extremity muscle treated required tenotomy later. Generally training was required after the procedure to obtain improved function. A representative sample of muscles treated, repeat procedures, and later surgery is discussed. The procedure is recommended for use in the management of spasticity in children as a way of improving function and/or care.
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PMID:Intramuscular neurolysis for spasticity in children. 47 67

We have studied 44 patients diagnosed of idiopathic Parkinson disease included in our database of rigid-akinetic syndromes. We have compared their demographic, environmental and clinical features with the ones that presented a group on 22 patients diagnosed of idiopathic Parkinson disease and had some first degree relatives with the same disease. Patients with familial Parkinson disease are distinguished from the ones that suffer from sporadic Parkinson disease because of an early start, greater consanguinity rate and greater frequency of a similar disease in their parents. Moreover, we have seen that familial Parkinson disease patients have drunk more water from wells during their lives than the ones that suffer sporadic Parkinson disease, present greater frequency of wide motoricity disorders, dystonia, night hypokinesia, fluctuations in relation to L-DOPA and greater frequency of early going grey. We have not found either epidemiologic data which could explain the appearance of familial cases or environmental causes which could produce familial Parkinson disease. Clinical differences between the two groups are likely due to an early start of symptoms in familial Parkinson disease cases. According to our data we could not conclude that between familial and sporadic Parkinson disease are significant differences in to justify two well-defined diseases. Even, the familial presentation of idiopathic Parkinson disease could be the normal form of Parkinson disease if long survival was a favourable factor of disease onset in pre-symptomatic persons.
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PMID:[Clinical and epidemiologic characteristics of familial Parkinson disease]. 209 60

Rats were administered equivalent doses of haloperidol for either 28 days or 8 months using one of two different drug regimens: intermittent (i.e., weekly injections) or continuously (via drinking water and osmotic mini-pumps). Oral movements were determined by human observers and by a computerized video analysis system, which determined number and amplitude of jaw openings and closings (computer-scored movelets "CSMs") as well as the slope (amplitude/duration) and frequency spectrum (fourier transform) of oral activity. The two drug groups developed distinctively different changes over time. Continuous administration resulted in late-onset oral activity changes at 1-3 Hz and withdrawal increases in CSMs, a pattern expected of tardive dyskinesia. Intermittent treatment produced a primed dystonia-like pattern: large amplitude CSMs which had steep onset slopes and a peak energy at 4-7 Hz. These results demonstrate the importance of drug regimen in determining the type of neuroleptic-induced dyskinesias which develop with prolonged neuroleptic treatment in rodents.
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PMID:Intermittent and continuous haloperidol regimens produce different types of oral dyskinesias in rats. 231 37

The article contains results of clinical studies of dimethylsulfoxide (DMSO) therapeutic application at vibration disease (VD) cases caused by local vibration and in comparison with the generally accepted complex therapy. 30% DMSO water solution skin compresses were used applied to the affected zones of the upper extremities for 1-1.5 hours daily with 12-15 procedures in the whole course. It was established that DMSO effects are positive in most VB manifestations: regional angiodystonia, sensor and vegetative--sensor polyneuropathy, arthroses, and particularly in cases of muscle dystonia and myodistrophy, humeroscapular periarthrosis. This kind of technique simplifies VD therapy as it excludes physiotherapy procedures and limits medication to a great extent, doing with no drugs at all in some cases. Treatment costs and clinical course duration are also lowered.
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PMID:[Dimethyl sulfoxide in the therapy of vibration disease]. 261 22

We measured the kinetic constants for the unidirectional influx of L-DOPA into red blood cells of patients with Parkinson's disease (seven patients), Huntington's disease (seven patients), and other extrapyramidal diseases (11 patients), and in five controls. Influx consisted of two components with low affinity and high exchange capacity. In individual subjects, the L-DOPA concentration giving half-maximal influx (Km) varied between 0.04 and 2.19 mM, and the maximum velocity (Vmax) of the saturable transport component was between 20 and 578 mumol/l cell water/h, which is compatible with the neutral amino acids of low affinity for the transport system. The range of Kd (the first-order rate constant for the unsaturable component) was between 0.11 and 0.36 hour-1. There was no gross deficit of the L-DOPA uptake process in patients with Parkinson's disease, Huntington's disease, dystonia, or other extrapyramidal diseases.
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PMID:Normal erythrocyte uptake of L-DOPA in Parkinson's, Huntington's, and related diseases. 622 Dec 1

Correction of some risk factors of atherosclerosis was tried in 247 patients with neurocirculatory dystonia who received dietary sea polyunsaturated fatty acids (PUFA) or balneotherapy (carbon dioxide arsenic mineral baths). As shown by assessment of clinico-functional characteristics, response of the microcirculatory bed, lipid metabolism, dietary PUFA and carbon dioxide arsenic mineral water have a positive effect on arterial hypertension, obesity and hyperlipidemia and thus can be used for primary prophylaxis of atherosclerosis.
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PMID:[Atherosclerosis: feasibility of non-pharmacological correction of some risk factors]. 1023 42

Tetrahydrobiopterin (BH4) is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GCH), 6-pyruvoyltetrahydropterin synthase (PTS), and sepiapterin reductase (SPD). GCH is the rate-limiting enzyme. BH4 is a cofactor for three pteridine-requiring monooxygenases that hydroxylate aromatic L-amino acids, i.e., tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and phenylalanine hydroxylase (PAH), as well as for nitric oxide synthase (NOS). The intracellular concentrations of BH4, which are mainly determined by GCH activity, may regulate the activity of TH (an enzyme-synthesizing catecholamines from tyrosine), TPH (an enzyme-synthesizing serotonin and melatonin from tryptophan), PAH (an enzyme required for complete degradation of phenylalanine to tyrosine, finally to CO2 + H2O), and also the activity of NOS (an enzyme forming NO from arginine), Dominantly inherited hereditary progressive dystonia (HPD), also termed DOPA-responsive dystonia (DRD) or Segawa's disease, is a dopamine deficiency in the nigrostriatal dopamine neurons, and is caused by mutations of one allele of the GCH gene. GCH activity and BH4 concentrations in HPD/DRD are estimated to be 2-20% of the normal value. By contrast, recessively inherited GCH deficiency is caused by mutations of both alleles of the GCH gene, and the GCH activity and BH4 concentrations are undetectable. The phenotypes of recessive GCH deficiency are severe and complex, such as hyperphenylalaninemia, muscle hypotonia, epilepsy, and fever episode, and may be caused by deficiencies of various neurotransmitters, including dopamine, norepinephrine, serotonin, and NO. The biosynthesis of dopamine, norepinephrine, epinephrine, serotonin, melatonin, and probably NO by individual pteridine-requiring enzymes may be differentially regulated by the intracellular concentration of BH4, which is mainly determined by GCH activity. Dopamine biosynthesis in different groups of dopamine neurons may be differentially regulated by TH activity, depending on intracellular BH4 concentrations and GCH activity. The nigrostriatal dopamine neurons may be most susceptible to a partial decrease in BH4, causing dopamine deficiency in the striatum and the HPD/DRD phenotype.
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PMID:Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin. 1032 73

Recent studies in mutant hamsters (dt(sz)), an animal model of primary paroxysmal dystonia, indicated that altered function of the gamma-aminobutyric acid (GABA)ergic system plays a critical role in the pathogenesis of dystonia. In the present study, dt(sz) hamsters were chronically treated with phenobarbital, which has been found to exert antidystonic effects in mutant hamsters after acute administration. In untreated dt(sz) hamsters, the severity of dystonia follows an age-dependent time course with a maximum between the 30th and 40th day of life, followed by a continuous decline of severity until complete remission occurs at the age of about 70 days. In contrast to acute effects, chronic treatment with phenobarbital via drinking water starting at an age of 21 days (i.e., after weaning) worsened dystonia and retarded the spontaneous remission. The unexpected prodystonic effect was more marked after administration of higher doses and when chronic treatment with phenobarbital started at an age of 1 day (neonatal administration via breast milk). After withdrawal of phenobarbital at the age of 70 days, the severity rapidly declined in all treated groups. When phenobarbital was readministered 1 week later, the hamsters again exhibited severe dystonia. The mechanism of these unexpected findings is unknown. Tentatively, activity-dependent GABA-mediated excitation caused by chronic treatment with phenobarbital may be important for the prodystonic effects under pathological conditions in dt(sz) hamsters.
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PMID:Paradoxical aggravation of paroxysmal dystonia during chronic treatment with phenobarbital in a genetic rodent model. 1084 33

A toxin produced by legumes of the genus Astragalus and Arthrinium fungi, 3-NPA is a suicide inhibitor of succinate dehydrogenase and causes acute encephalopathy and late onset dystonia. It has been suggested that dopamine (DA) toxicity plays a role in 3-NPA induced brain damage. In order to simulate natural conditions of toxicant intake, adult, male, Sprague-Dawley rats were exposed to 3-NPA weekly for 24-h periods at 10 and 20 mg/40 ml in drinking water. This dosing regimen continued for 3 months with animals from both high and low dose groups sacrificed at the end of each month. Dopamine and its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assessed by HPLC-EC in the frontal cortex (FC) and caudate nucleus (CN). Increases of DA concentration were seen in both low and high dose groups in the CN after 1 and 3 months of dosing and in the FC after 2 months of exposure. An increase in DA turnover was observed in the CN of the high dose group following 2 months of dosing. Data suggest an activation of the dopaminergic system after long-term, intermittent exposure to 3-NPA. The production of radical oxygen species associated with DA metabolism may contribute to 3-NPA-induced neurotoxicity.
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PMID:Dopamine toxicity following long term exposure to low doses of 3-nitropropionic acid (3-NPA) in rats. 1090 28

Prolonged exposure to manganese in mammals may cause an extrapyramidal disorder characterized by dystonia and rigidity. Gliosis in the pallidal segments underlies the well-established phase of the intoxication. The early phase of the intoxication may be characterized by psychic, nonmotor signs, and its morphological and electrophysiological correlates are less defined. In a rat model of manganese intoxication (20 mg/ml in drinking water for 3 months), neither neuronal loss nor gliosis was detected in globus pallidus (GP). However, a striking vulnerability of manganese-treated GP neurons emerged. The majority of GP neurons isolated from manganese-treated rats died following brief incubation in standard dissociation media. In addition, patch-clamp recordings in the whole-cell configuration were not tolerated by surviving GP neurons. Neither coeval but untreated GP neurons nor striatal ones manifested analogous susceptibility. Using the perforated-patch mode of recording we attempted at identifying the functional hallmarks of GP vulnerability: in particular, voltage-gated calcium currents and glutamate-induced currents were examined. Manganese-treated GP neurons exhibited calcium currents similar to control cells aside from a slight reduction in the dihydropyridine-sensitive current facilitation. Strikingly, manganese-treated GP cells--but not striatal ones--manifested peculiar responses to glutamate, since repeated applications of the excitatory amino acid, at concentrations which commonly promote desensitizing responses, produced instead an irreversible cell damage. Possible mechanisms are discussed.
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PMID:Selective vulnerability of pallidal neurons in the early phases of manganese intoxication. 1115 18


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