Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was carried out to clarify whether levodopa should be started early or late in the course of Parkinson's disease. In this study, 122 patients treated with levodopa over 14 years were included. The time course of each of the four major signs (rigidity, static tremor, akinesia and postural instability) and Yahr stage was investigated in three groups, Yahr stage I/II group, Yahr stage III group and Yahr stage IV/V group, taking into consideration the time period preceding the initiation of levodopa therapy. When the time periods in years since onset of symptoms were matched, no significant differences were recognized among the three groups. There seemed to be no benefit in delaying levodopa therapy but, rather, levodopa therapy should be started as early as possible. The declining efficacy often recognized during levodopa therapy was thought probably due to progression of Parkinson's disease itself rather than to levodopa.
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PMID:Should levodopa therapy for Parkinson's disease be started early or late? Clinical course of the major tetrad in 122 parkinsonian patients treated with levodopa over 14 years. 272 44

The parkinsonian syndrome rests on the clinical tripod: akinesia, rigidity, tremor. Akinesia is the key symptom, broadly defined as a difficulty in initiating and performing movements in proportion to their complexity (sophisticated, simultaneous movements) and their duration (repetitive movements). The most frequent cause of the syndrome is Parkinson's disease. Although this diagnosis needs to be confirmed in pathological terms by the loss of neurons and the presence of Lewy's bodies in the substantia nigra, some clinical data enable it to be envisaged with a minimum of errors; these are pure parkinsonian triad, good response to dopatherapy and asymmetrical symptoms. The other causes of parkinsonian syndrome are usually related to the administration of neuroleptic drugs and to degenerative diseases with lesions that are more diffuse than those of Parkinson's disease. In Steele-Richardson-Olzewski disease a parkinsonian syndrome is associated with supranuclear ophthalmoplegia. Multiple systematized atrophy presents under three different clinical aspects: a parkinsonian syndrome without tremor and resistant to L-dopa, suggesting atrophy of the strionigral tract; a parkinsonian syndrome associated with a cerebellar syndrome, suggesting olivo-cerebellar-pontine atrophy, and Shy-Drager disease which includes primary dysautonomy and other neurological syndromes.
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PMID:[Parkinson's disease and parkinsonian syndromes]. 272 71

After a number of good years, most patients with Parkinson's disease are faced with various problems. Some of these are due to the progress of the underlying anatomico-biochemical process and others to interference of the disease with dopatherapy. Motor impairment takes multiple aspects: disturbances of equilibrium and gait, akinesia with unusual presentation, involuntary movements, fluctuations of the motor status. Mental disorders may appear as depressive syndrome, mental confusion and/or varying degrees of intellectual alterations. Despite these disorders, the treatments that are currently available give these patients a normal life expectancy.
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PMID:[Development of Parkinson's disease]. 272 72

We examined correlates of depression in patients whose onset of Parkinson's disease (PD) began before age 55 (early-onset group) compared with patients whose onset was after age 55 (late-onset group). The early-onset group showed a significantly higher frequency of depression than the late-onset group. When both groups were matched for duration of the disease, the early-onset group still showed a significantly higher frequency of depression, whereas tremor, akinesia, and rigidity were significantly more severe in the late-onset group. A stepwise regression analysis showed that in the early-onset group, depression scores were significantly correlated with scores of cognitive impairment and duration of the disease, while in the late-onset group, depression scores were significantly correlated with impairments in activities of daily living. These data suggest that depression in patients with early-onset PD may have a different etiology than in patients with late-onset PD.
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PMID:Depression in patients with early versus late onset of Parkinson's disease. 234 6

The concentrations of somatostatin-like immunoreactivity (SLI) in lateral ventricular fluid of patients with extrapyramidal motor disease were determined by specific radio-immunoassay. Mean SLI levels were significantly lower in patients with Parkinson's disease (mean +/- SEM); 42.9 +/- 2.9 fmol/ml) and in patients with dystonic syndromes (39.4 +/- 3.2) than in patients with benign essential tremor (65.3 +/- 9.7). The lowest levels were found in patients with athetosis (34.7 +/- 5.4). In parkinsonian patients somatostatin levels correlated with the degree of akinesia, rigidity and autonomic disturbances.
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PMID:Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease. 286 2

Depressive mood is frequently associated with Parkinson's syndrome, but it may also occur as a precursor of this disease. As regards the subtypes of Parkinson's disease, the frequency of depressive states is significantly higher in the type dominated by akinesia and rigidity than in the type dominated by tremor. On the basis of biochemical changes, certain aspects of the depression can be successfully treated by substitution therapy: L-dopa medication may increase the reduced dopamine values in the striatum, thereby improving drive. Substitution with L-tryptophan raises the lowered serotonin values in the reticular formation, which may influence sleep disturbances. The changes of basic mood, however, which are characteristic of depression, such as cheerlessness and apathy, are the dopamine of antidepressive medication; only these drugs can re-establish the biochemical balance to a large extent.
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PMID:[Depression and Parkinson syndrome]. 287 39

Administration of the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces a parkinsonian syndrome in primates. Intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the common marmoset (Callithrix jacchus) produced symptoms of rigidity, akinesia and tremor which persisted for at least one month. However, after this time, considerable behavioural recovery occurred, although animals were still severely bradykinetic compared with controls. Marmosets were allowed to survive for 1, 3 1/2 or 7 months prior to histological and immunocytochemical analysis. Detection of catecholaminergic neurons using antibodies directed against the enzyme tyrosine hydroxylase revealed a profound (80%) loss of dopaminergic cells from the substantia nigra one month after initiation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. This was accompanied by a severe gliosis. Fewer cells were lost from the adjacent ventral tegmental area (45%), but dopamine-containing cells in other brain areas were not obviously affected. At longer survival times the substantia nigra was less damaged, with a proliferation of glia in the pars compacta and a loss of approximately 20% of the dopaminergic perikarya. Using immunohistochemical techniques, the distribution of neuropeptides substance P, [Met]enkephalin and dynorphin 1-17-like immunoreactivity were examined and found to exhibit distinctive patterns in the marmoset substantia nigra. The integrity of these systems appeared intact at all times after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. These results support the hypothesis that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a clinical syndrome, indistinguishable from Parkinson's disease, via a selective destruction only of neurons with perikarya in the substantia nigra pars compacta and the ventral tegmental area. The findings that the peptidergic input to these cells together with most non-nigral dopaminergic cell groups are not damaged, indicate that the selectivity of the lesion produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine appears greater than that seen in idiopathic Parkinson's disease. The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset may not be permanent since both behavioural and biochemical recovery were observed after several months.
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PMID:An immunohistochemical study of the acute and long-term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset. 289 93

Administration of MPTP (1-4 mg/kg ip daily for 5-7 days) to common marmosets induced persistent parkinsonian motor deficits. The subcutaneous administration of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine; 1-4 micrograms/kg] caused a dose-dependent reversal of the akinesia and incoordination of movement. Similarly, oral administration of (+)-PHNO (5-20 micrograms/kg) caused an equivalent reversal of the motor abnormalities. No dyskinetic phenomena were induced by (+)-PHNO on oral or subcutaneous administration. Oral or subcutaneous administration of (+)-PHNO to normal control marmosets also increased the usual repetoire of motor behaviour, but this was not as marked as in MPTP-treated animals. (+)-PHNO is a potent dopamine agonist drug of potential use in the treatment of Parkinson's disease.
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PMID:Antiparkinsonian activity of (+)-PHNO in the MPTP-treated common marmoset. 290 19

We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and primate models of Parkinson's disease as an experimental approach to the treatment of levodopa-induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by 6-hydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24-48 h after infusion and whose intensity progressively decreased over the period of 1 week. [3H]Spiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphine were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly. Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals.
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PMID:Continuous intracerebroventricular infusion of dopamine and dopamine agonists through a totally implanted drug delivery system in animal models of Parkinson's disease. 290 48

Rats with experimentally induced DA deficiency were treated with intracerebroventricular administration of (+)-4-propyl-9-hydroxynaphthoxacine (PHNO) through a totally implanted chronic delivery system which delivered PHNO, 0.9 microgram/h, continuously for up to 2 weeks. Rats with 6-OH-DA induced unilateral nigrostriatal lesion showed, after PHNO infusion, a potent and persistent contralateral turning behavior (8-11 turns/min) which was not present in vehicle-infused animals. The intensity of spontaneous and apomorphine-induced rotation did not decrease after 2 weeks of continuous infusion, suggesting that tolerance to PHNO or to other dopamine agonists did not develop. The magnitude of the spontaneous turning behavior in PHNO-infused animals correlated well with the baseline response to apomorphine (r = 0.505, p less than 0.025). Rats implanted with pumps delivering PHNO or vehicle were treated with reserpine, 0.5 mg/kg/day for 14 days. Vehicle-infused, reserpinized animals had a severe akinesia and weight loss during the experimental period (motor activity, measured in counts per minute was reduced to 5-10% of baseline levels, and body weight to 50% of baseline levels). PHNO-infusion partially restored activity to 60% of baseline counts and reduced the severity of weight loss. PHNO effects were observed for as long as the infusion was maintained. No side effects were observed. Intracerebroventricular infusion of PHNO may be an alternative experimental approach to untreatable motor fluctuations in Parkinson's disease.
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PMID:The effect of intracerebroventricular infusion of (+)-4-propyl-9-hydroxynapthoxacine (PHNO) through a totally implanted drug delivery system in rats with dopamine deficiency. 290 50


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