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)

Recently, we demonstrated amelioration of behavioral deficits associated with 6-hydroxydopamine-induced hemiparkinsonism by transplanting rat testis-derived Sertoli cells into adult male rat brains. In the present study, we used adult female hemiparkinsonian rats to investigate whether the beneficial effects of transplantation of Sertoli cells may be differentially affected by gender of the animal transplant recipient. At 1 month posttransplantation, animals transplanted with Sertoli cells showed functional recovery as revealed by significant reductions in apomorphine-induced rotational behavior and asymmetrical elevated body swing behavior. Control animals that received medium alone did not display any visible behavioral recovery. These results suggest that transplantation of Sertoli cells is not male hormone-dependent and further support the use of these cells as a graft source for Parkinson's disease and other neurological disorders.
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PMID:Intracerebral transplantation of testis-derived sertoli cells promotes functional recovery in female rats with 6-hydroxydopamine-induced hemiparkinsonism. 939 81

Parkinson's disease (PD) is a common neurological illness and various degrees of depression frequently complicate its course. Risk factors for developing depression with PD include right-sided hemiparkinsonism, akinesia, increased severity of disability, anxiety and psychosis. Onset of parkinsonism at a younger age, female gender and the use of levodopa are arguable risk factors. Depression may be difficult to diagnose in patients with PD because the signs of the 2 disorders overlap. In addition, patients with atypical PD more commonly have depression than patients with classical PD presentations. Antidepressant response to antiparkinsonian treatment has been limited. Enhancement of catecholamine levels in the CNS by selegiline (deprenyl), a monoamine oxidase (MAO) type B inhibitor, has shown potential antidepressant as well as neuroprotective effects. Other MAO inhibitors have shown antidepressant efficacy in animal models but have not been well tolerated by patients with PD. A catechol-O-methyltransferase (COMT) inhibitor combined with an MAO inhibitor might synergistically maximise the levels of catecholamines in the CNS. Antidepressant medications used in patients without PD include tricyclic antidepressants (TCAs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), but only TCAs have been carefully studied for their antidepressant effects in PD. Electroconvulsive therapy has proven efficacy as antidepressant therapy in patients with PD, and transcranial magnetic stimulation has provided temporary relief of depression under experimental conditions. Adverse effects of polypharmacy in the attempted treatment of depression in patients with PD are common in the elderly. A 'serotonin syndrome' has occurred frequently enough to preclude the coadministration of selegiline with SSRIs or TCAs, and multiple interactions between antiparkinsonian and antidepressant medications further complicate treatment strategies in patients with PD. An algorithmic approach to the pharmacological treatment of depression is described in this article.
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PMID:Depression in Parkinson's disease. Pharmacological characteristics and treatment. 946 87

In order to investigate sensorimotor processing and force development in Parkinson's disease, 16 patients, four patients with hemiparkinsonism and 12 age-matched normal subjects were assessed during lifting and holding of an object in a precision grip between thumb and forefinger, or holding the object in this grip at a fixed height above a table. In the former case, object loading could be changed between lifts without warning. In the latter case, unexpected step load changes to the object were applied to the object with a torque motor. All procedures could be applied with or without visual control of the hand and the object. Normal subjects lifted an unpredictable load employing the grip force parameters used in the preceding lift. If a load change was encountered, the parameters became adapted to the new conditions during the lift, modulating grip forces to match the loading. Parkinsonian patients retained this strategy and the ability to regulate grip forces according to load. Under all conditions, however, parkinsonian subjects developed abnormally high grip forces in both the lift and the hold phase, although the ratio of these forces remained normal. Lifting height was normal in parkinsonian subjects, but the duration of the lifting task was significantly prolonged, due to a marked slowing in the rate of grip force development in the lead-up to object lift-off and to prolongation of the movement phase. Forewarning of object loading, with or without visual control, did not reduce timing deficits or improve the rate of grip force development. However, it did allow parkinsonian subjects to reduce the safety margin significantly. Responses to step load changes imposed during holding without visual control showed minor abnormalities in the parkinsonian patients: onset latencies and EMG activity in the first dorsal interosseus and thenar muscles were normal up to 140 ms after displacement. Subsequent EMG activity in the first dorsal interosseus remained largely normal, but activity later in the slip response (140-210 ms), subject to voluntary influence, was reduced in the thenar muscle. Differences were less marked under visual conditions, but remained significant. We concluded that the internal parameter set for lifting an object in a precision grip and the automatic processes adapting precision grip to actual conditions are intact in Parkinson's disease. However, parkinsonian subjects generate abnormally high grip forces and require longer than normal subjects to complete a lift, particularly with lighter loads. This deterioration in performance reflects both reduced effectiveness of sensorimotor processing and impairment in the rate of force development in Parkinson's disease.
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PMID:Precision grip and Parkinson's disease. 976 64

This study was aimed at determining the spatiotemporal distribution of event-related desynchronization (ERD) during self-paced voluntary movement in order to establish the interest of this method for the analysis of movement programming in Parkinson's disease. Desynchronization of mu rhythm was recorded 2 s before to 0.5 s after right then left self-paced voluntary wrist flexions from 11 leads covering the primary sensorimotor cortex (central), supplementary motor area (frontocentral) and parietal cortex (parietocentral). Recordings were obtained from ten control subjects, ten patients treated for Parkinson's disease (bilateral symptoms) and 20 patients presenting with right or left hemiparkinsonism before and after chronic administration of L-dopa. In the control group, ERD started over the contralateral primary sensorimotor cortex 1,750 ms before movement and was bilateral just before performance of the movement. In both treated and de novo Parkinson's disease groups, decrease in ERD latency (1,000 to 1,250 ms before movement) was only observed when movements were performed with the akinetic hand and corresponded to a decrease in motor cortical activity. This confirmed that programming of movement is affected in Parkinson's disease. Earlier ERD with central ipsilateral distribution were also observed, suggesting that other cortical areas might be activated to compensate for dysfunction of movement programming and to increase the level of cortical activity required for performance of the movement. The administration of L-dopa to de novo hemiparkinsonians patients resulted in increased ERD latency over contralateral and ipsilateral central areas. As in the treated Parkinson's disease group, frontocentral ERD could also be recorded. L-dopa would thus partially restore the affected motor programmation and modulate cortical activation in both supplementary motor area and primary motor cortex, the later receiving more afferences from basal ganglia.
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PMID:[Event-related desynchronization and Parkinson disease. Importance in the analysis of the phase of preparation for movement]. 1009 19

We studied the sequential changes in second messenger systems in the striatum and substantia nigra (SN) after 6-hydroxydopamine lesions of the medial forebrain bundle in rats. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. [3H]Phorbol-12, 13-dibutyrate (PDBu), [3H]forskolin and [3H]rolipram were used to label protein kinase C (PKC), adenylyl cyclase and calcium/calmodulin-independent cyclic-AMP phosphodiesterase, respectively. The degeneration of nigrostriatal pathway produced a significant increase in [3H]PDBu binding in the ventromedial part of the ipsilateral striatum from 2 to 8 weeks postlesion. In the contralateral side, [3H]PDBu binding showed a transient increase in the SN only 4 weeks after lesioning. [3H]Forskolin binding showed a significant increase in the ipsilateral and contralateral striatum from 2 to 4 weeks postlesion. In the ipsilateral SN, a significant increase in [3H]forskolin binding was observed at 4 weeks after lesioning. However, no significant change in [3H]forskolin binding was observed in the contralateral SN during postlesion. On the other hand, [(3)H]rolipram binding showed no conspicuous alteration in the brain during postlesion. These results demonstrate that rats made hemiparkinsonism by unilateral 6-hydroxydopamine injection have a significant increase in [3H]PDBu and [3H]forskolin binding in the striatum and/or SN, whereas no significant change in [3H]rolipram binding is observed in these areas during postlesion. Our findings also suggest that the increase in [3H]forskolin binding is more pronounced than that in [3H]PDBu binding in the brain after unilateral 6-hydroxydopamine injection. Thus, our studies may provide valuable information concerning degeneration of the nigrostriatal pathway such as Parkinson's disease.
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PMID:Alterations of second messenger systems in the rat brain after 6-hydroxydopamine lesions of the medial forebrain bundle. 1042 76

Several neurological conditions have been reported to be associated with peripheral or central deficits of olfactory system. In recent years particular emphasis has been placed on the early and severe olfactory impairment in Parkinson's disease (PD), in which limited neuropathological studies have revealed a marked dopaminergic deficit in the olfactory tubercles. Moreover, indirect evidence suggests that dysfunction of the dopaminergic pathways from mesencephalon to the piriform cortex may play a role in olfactory impairment in PD. A large number of clinical studies have reported that olfactory loss in idiopathic PD is bilateral, present in hemiparkinsonism, unrelated to the stage or clinical subtype of the disease, and independent of antiparkinsonian medication. In addition, major olfactory alterations have been reported in familial PD and dementia with Lewy bodies but not in progressive supranuclear palsy and essential tremor. These findings might stimulate further research targeted to determine the biological substrate of dissimilar olfactory performances in these movement disorders. The present review summarizes standardized procedures for the assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants), and memory (recognition of a substance previously smelled). Specific suggestions concerning the psychometric and neuropsychological evaluation of PD patients are provided.
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PMID:Olfaction in Parkinson's disease: methods of assessment and clinical relevance. 1075 Nov 9

We found that in Parkinson's disease (PD) the levels of various cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-6, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, TGF-beta1] were significantly increased in the striatum (caudate and putamen) of the postmortem brain and in ventricular or spinal cerebrospinal fluid (VCSF, LCSF). Furthermore, the levels of the apoptosis-related proteins such as bcl-2 and soluble Fas (sFas) in the striatum were also elevated in PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonism mice, the levels of IL-1beta in the striatum were significantly increased, but those of nerve growth factor (NGF) were significantly decreased, compared with control mice. In hemiparkinsonism rats produced by injection of 6-hydroxydopamine (6-OHDA) into one side of the median forebrain bundle, the levels of TNF-alpha in the 6-OHDA-treated side were increased in the striatum and substantia nigra, but not in the cerebral cortex, compared with those in the control side. Repeated administration of L-DOPA in the 6-OHDA-treated rats did not change the TNF-alpha levels in the control side and in the 6-OHDA-treated side in the substantia nigra, striatum, and cerebral cortex. Our results suggest that the changes in the levels of cytokines, neurotrophins, and apoptosis-related proteins in the nigrostriatal regions of PD may be involved in apoptosis and degeneration of the nigrostriatal DA neurons.
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PMID:Cytokines in Parkinson's disease. 1112 4

Sertraline, a serotonin reuptake inhibitor, has been used to treat depression and has rarely been associated to Parkinsonism. The disease usually appears in old people a few days after sertraline administration and disappears very quickly after its withdrawal. We report a case of a woman, 81-year-old, who presented with hemiparkinsonism after long-term administration of sertraline at a dose of 100 mg/day. The symptoms disappeared 3 months after the withdrawal of the drug. However, without further administration of the drug for 14 months, the patient presented with Parkinson's disease, but responded well to levodopa.
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PMID:Parkinsonism and Parkinson's disease associated with long-term administration of sertraline. 1135 May 33

Some patients with Parkinson's disease (PD) suffer from autonomic dysfunction, even in the early stage of the disease. We examined the skin wrinkling response following immersion of the hands in warm water in 18 patients with hemiparkinsonism. This test evaluates the function of the sympathetic autonomic system. Mean age of the patients was 61 +/- 10 and mean disease duration 5.5 +/- 3.5 years. Both hands of each patient were immersed in warm water for 30 minutes and the number of skin ridges of the fingertip of each finger was counted. The results of each hand were compared to those of nine healthy controls. The mean number of the ridges of the less affected hand was significantly decreased as compared to the affected hand and controls (6.1 +/- 6.8 vs 13.1 +/- 6.8 and 15.3 +/- 8.5, respectively; P < 0.01). These results suggest that autonomic dysfunction is prevalent in the less affected side of patients with PD and can be simply tested by the skin response test.
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PMID:Abnormal skin wrinkling in the less affected side in hemiparkinsonism-a possible test for sympathetic dysfunction in Parkinson's disease. 1168 82

Non-demented patients with Parkinson's disease (PD), especially if they are high functioning and early in the course of their disease, usually exhibit mild deficits in anterograde recall memory for verbal and non-verbal material, visuospatial reasoning, visuomotor construction, temporal ordering and sequencing. Impairments in problem solving and verbal fluency tests may also occur. PD patients with predominantly right-sided symptoms usually exhibit more severe difficulties with verbal than with non-verbal tasks. We report a case of a highly educated right-handed man with very mild right-sided hemiparkinsonism who never received anti-Parkinsonian or other psychoactive medication. Our patient showed anterograde and retrograde amnesia for faces and spatial locations and difficulties on complex visuospatial tasks that required manual responses, but normal to above average performance on all other cognitive tests. The specific pattern of cognitive loss early in PD may depend on which spatial, facial or verbal pre-frontal striatal circuits are deprived of their dopaminergic inputs.
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PMID:Cognition in a patient with very mild right-sided hemiparkinsonism. 1199 83


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