Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined whether the N-methyl-D-aspartate antagonist MK-801 (dizocilpine) would reverse parkinsonism or potentiate the effects of L-dopa in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In contrast to its effect in rodent models, treatment with MK-801 (0.1 mg/kg) caused bradykinesia and ataxia in parkinsonian primates, but no locomotor stimulation. Coadministration of MK-801 (0.1 mg/kg) with L-dopa (20 mg/kg) induced marked dystonia accompanied by bradykinesia and ataxia. Dystonia was not induced by either treatment given alone. These findings indicate that MK-801 should not be advocated as an adjunct to dopamine agonist therapy in Parkinson's disease.
 ...
PMID:Dystonia induced by combined treatment with L-dopa and MK-801 in parkinsonian monkeys. 164 62

We have compared the ability of phencyclidine (PCP)-like or sigma ligands to induce psychomotor effects in primates. In squirrel monkeys, administration of MK-801 (0.001-0.1 mg/kg), PCP (0.03-0.3 mg/kg), (+)-SKF10047 (0.001-3.0 mg/kg) or (-)-SKF10047 (0.1-10 mg/kg) induced ataxia, head weaving and bradykinesia. In contrast, treatment with the selective sigma ligand (+)-pentazocine using doses up to 20 mg/kg failed to induce any overt behaviours. The order of potency for induction of these behaviours was: MK-801 greater than PCP greater than (+)-SKF10047 greater than (-)-SKF10047 much greater than (+)-pentazocine. In rhesus monkeys treatment with MK-801 (0.01-0.04 mg/kg), PCP (0.05-0.2 mg/kg), (+)-SKF10047 (0.75-3.0 mg/kg) or (+)-pentazocine (1-10 mg/kg), disrupted performance of a spatial delayed response task. The potency to induce cognitive disruption was positively correlated with affinity for [3H]MK-801, but not [3H](+)-SKF10047, binding sites in vitro. These findings indicate that the psychomotor and cognitive effects of PCP-like and sigma ligands in primates are mediated through interactions at NMDA, not sigma, receptors.
 ...
PMID:Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates. 164 81

A 40-year-old woman developed high fever and headache. Five days later, she was admitted because of consciousness disturbance and tremulous movements in upper extremities. The paired sera showed more than fourfold elevation in complement fixation titer to Japanese encephalitis virus. She was diagnosed as Japanese encephalitis from the clinical features and serological tests. Magnetic resonance imaging (MRI), which was performed about seven months after the onset, revealed abnormal intensity areas bilaterally in the thalamus, hippocampus, substantia nigra, globus pallidus and white matter around the lateral ventricle. Eight months after the onset, she was left with bradykinesia, disturbance of rightening reflex, emotional lability and impairment of recent memory with a long period of amnesia, including not only her illness and subsequent events but also about several years before her illness. The characteristic memory dysfunction seems to be due to disorder of bilateral hippocampus, where MRI revealed abnormal intensity areas. And disorder of medial thalamic nucleus would be related to emotional liability. The relation between the clinical features and MRI findings is also discussed.
 ...
PMID:[A case of Japanese encephalitis demonstrating characteristic changes in MRI]. 166 72

Cynomolgus monkeys received intracarotid injections of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5-mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.
 ...
PMID:Intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration: biochemical and behavioral observations in a primate model of hemiparkinsonism. 169 Feb 67

Parlodel-SRO is a newly developed slow-release formulation of bromocriptine, which prevents initial plasma peak--a known source of adverse events--and extends the half-life of the compound, an interesting feature for the management of motor symptoms in Parkinsonians. This study was designed to determine the best daily administration schedule for 30 mg Parlodel-SRO in 18 parkinsonians previously treated with levodopa and standard Bromocriptine (Br). The 30 mg dose was replaced from one day to the next, in a randomized, double-blind latin square design trial. Three consecutive 7-day courses were implemented, during which a total daily dose of 30 mg P-SRO was administered in one dose, two intakes (b.i.d.) and three intakes, (t.i.d.) respectively. The b.i.d. schedule produced the best improvement in UPDRS scores, especially as to postural stability, walking, bradykinesia; it also provided greater pharmacological stability throughout the assessment day. Adverse event analysis was not in favor of a single daily dose. It appeared that P-SRO administered in two 15 mg intakes (morning and evening) produces the best benefit-risk ratio in Parkinsonians who were already being treated with levodopa.
 ...
PMID:Comparison of three regimens of Parlodel-SRO in levodopa-treated parkinsonians: a randomized double-blind crossover study. 174 6

Premovement silence (PMS) of tonic agonist electromyographic activity (EMG) preceding a maximum effort elbow extension was studied in eight bradykinetic Parkinson patients. The occurrence and duration of PMS have been shown to be significantly correlated with peak acceleration of movement in normal subjects. To determine if inability to silence the EMG prior to the initial agonist burst may contribute to bradykinesia of Parkinson's disease, patients maintained elbow extension against a tonic load on triceps, and in response to a tone performed a maximum effort elbow extension. All eight patients showed some trials (mean = 30%) with PMS. However, neither the incidence of PMS nor its duration were significantly correlated with mean peak acceleration. A significant correlation was found between the incidence of abnormal initial agonist bursts, called "segmented bursts," and mean peak acceleration. We conclude that ability to silence the agonist muscle prior to movement is not strongly associated with bradykinesia in Parkinson's disease.
 ...
PMID:Premovement silence of EMG activity prior to movement in Parkinson patients. 174 79

A 29 year old student of chemistry took 50 ml of a 1% potassium cyanide solution (500 mg) in attempted suicide. He became comatose, mydriatic and was admitted to hospital in an apneic state. He woke up after seven hours and developed Parkinsonism in the following weeks. This regressed slowly in the second month after the poisoning apart from dysarthria, bradykinesia of the upper limbs and very brisk monosynaptic reflexes. Three weeks after the intoxication, CCT was largely normal, and there was CSF-dense hypodensity in both putamina after five months. Sharply delimited signal elevation in T2 corresponding to the two putamina was detected in the MRI eight weeks and five months after ingestion of the poison.
 ...
PMID:Extrapyramidal disturbances after cyanide poisoning (first MRT-investigation of the brain). 175 44

Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system. Modifications of their synthesis occur following receptor blockade or deafferentiation by surgical lesions. This concept should provid answers to some remaining open questions in human pathology especially in degenerative diseases of the basal ganglia. In a severely atrophied striatum we observed a selective increase in the number of detectable striatal substance P and met-enkephalin neurones which exhibited a striking increase in the intensity of labelling. This increase, instead of the well established reduction of substance P and enkephalins in the atrophied striatum of Huntington's disease, could explain the absence of choreoathetosis which was replaced by rigidity and bradykinesia in the patient. The absence of choreoathetosis, despite severe striatal atrophy, is described in several basal ganglia diseases and could also be related to neurotransmitter or neuropeptide plasticity rather than due to the primary lesion.
 ...
PMID:Does the absence of clinical expression of choreoathetosis, despite severe striatal atrophy, correlate with plasticity of neuropeptide synthesis? 175 57

Peculiarities of excitation and inhibition in ventral lateral and ventral anterior thalamic neurons were studied in cats with movement disorders (bradykinesia and muscle rigidity) induced by injury of nigrostriatal dopaminergic neurons with neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5 mg/kg daily, intramuscularly for five days). As was shown in chronic experiments, mean discharge frequency of neurons related to initiation of upper limb movements increased. Excitation of these neurons coincided with movement initiation, flexion and extension becoming more prominent and prolonged as compared with normal animals. In parallel to those changes, bradykinesia developed. In acute experiments performed under ketalar anaesthesia and myorelaxine immobilization it was found that neurotoxin caused a decrease of the inhibition duration and effectiveness in relay and non-relay thalamic motor nuclei neurons. The inhibition deficiency was accompanied by a shortening of latencies of orthodromic responses evoked by red nucleus stimulation. Two days after the last neurotoxin injection, light microscope examination revealed that about 48% of neurons located in the pars compacta of substantia nigra were destroyed. Electron microscopic analysis showed hydropic changes in perykaria and dendrites in most neurons of the substantia nigra pars compacta that are typical of the light type of degeneration. Pathomorphological processes in the synaptic apparatus were also found. The content of dopamine in the caudate nucleus fell to 30% as compared with intact animals. The suggestion is made that the deficiency of inhibition developed in motor thalamic neurons in response to nigrostriatal system destruction results from attenuation of dopamine-modulated direct GABAergic nigrothalamic influences and/or might be connected with increased inhibition of inhibitory interneurons of the same thalamic nuclei conditioned by pallidum disinhibition.
 ...
PMID:Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced injury of dopaminergic nigrostriatal system on movement components of the instrumental reflex and motor thalamic neurons' reactions in the cat. 176 81

The paper is concerned with a pilot detailed study of a single 24-h sleep deprivation (SD) in parkinsonism patients (n-35). The score estimation of the disease clinical signs demonstrated diminution of rigidity, bradykinesia, gait defects as well as of the total score of the patients condition severity. The clinical observations were verified by computer processing of motor tests. SD proved antidepressant in parkinsonism patients. The combination of drug treatment with SD permits a 2-fold and 50% decrease in the treatment duration and daily dose, respectively. A test is proposed for assessing tonicity of facial muscles.
 ...
PMID:[Effects of sleep deprivation in patients with parkinsonism]. 176 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>