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 effect of a new dopaminergic agonist, piribedil, was studied in 16 patients with Parkinson's disease and compared with placebo and L-DOPA. Piribedil appeared to have a moderate therapeutic effect that was significantly less than that of L-DOPA. Tremor appeared to be the main clinical feature to benefit. Nausea, vomiting, and somnolence were most frequent during the buildup of treatment and confusion and hallucinations during long-term treatment. Piribedil caused a significant decrease in probenecid-induced accumulation of HVA in the CSF, suggesting reduced turnover of endogenous dopamine in the brain. There was a significant relationship between dopamine receptor activation by piribedil and improvement of parkinsonian disability.
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PMID:Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. 109 75

Neuropeptide Y, one of the most abundant polypeptides within the nervous system, is co-stored with catecholamines, especially norepinephrine (NE), thus suggesting its possible involvement in pathologies characterized by a noradrenergic impairment. In Parkinson's disease (PD), as well as in multiple system atrophy (MSA), a central noradrenergic deficit has been demonstrated, and in the dementia of Alzheimer type (DAT) an impaired noradrenergic transmission has been postulated. In this study we determined CSF NE and MHPG levels in 29 PD, 15 MSA, 22 DAT patients and in 36 controls, while CSF NPY-immunoreactivity (NPY-ir) levels were measured in 10 PD, 7 MSA, 10 DAT patients and 20 controls. PD, MSA, and DAT patients showed a significant reduction in CSF NPY-ir and NE levels compared with controls, while CSF MHPG levels resulted in a reduction in only the MSA group. Furthermore, an inverse correlation between either NE or MHPG levels and the duration of the orthostatic hypotension was found in MSA patients while for DAT patients the MHPG levels were directly correlated to the severity of cognitive impairment, and inversely to the duration of illness.
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PMID:Cerebrospinal fluid norepinephrine, 3-methoxy-4-hydroxyphenylglycol and neuropeptide Y levels in Parkinson's disease, multiple system atrophy and dementia of the Alzheimer type. 132 Aug 91

Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use.
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PMID:Reactive oxygen species and the central nervous system. 140 8

We used two analytic methods (a multichannel coulometric electrode array with high-performance liquid chromatography, and gas chromatography-mass spectrophotometry) to measure CSF dopamine (DA) and its metabolites in mildly affected, unmedicated subjects with Parkinson's disease (PD). The mean (+/- SD) concentration of homovanillic acid (HVA), the most abundant product of DA turnover, was 164.57 +/- 95.05 nM. As sequential aliquots of CSF were collected from the first to 23rd ml, CSF HVA concentration almost doubled. After HVA, 3-O-methyldopa (3-O-MD) was the next most abundant compound. The summed concentrations of 3-O-MD, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, DA, DA-3-sulfate, homovanillol, and levodopa (LD) amounted to 12.6% of HVA. Concentrations of the DA metabolites did not correlate to a variety of indices of PD severity. The presence of LD and 3-O-MD may be indicators of DA synthesis and possibly could reflect compensatory processes among surviving dopaminergic neurons of the PD brain.
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PMID:Markers of dopamine metabolism in Parkinson's disease. The Parkinson Study Group. 143 20

Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.
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PMID:Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging. 154 14

Parkinson's disease (PD) is a common degenerative disease, but its etiology is still unknown. However, since the discovery of MPTP, many investigators have been interested in the mitochondrial function in PD. We investigated mitochondrial functions in PD patients using the methods which have successfully been applied to mitochondrial myopathies (MM), i.e. assay of lactate and pyruvate, measurement of muscle mitochondrial respiratory enzyme activities and Southern blot analysis of muscle mitochondrial DNA. Parkinson's disease patients did not differ from controls in the mean blood and CSF (cerebrospinal fluid) lactate and pyruvate levels at the basal resting state or during an aerobic exercise. But mitochondrial complex I activity of the skeletal muscle was significantly decreased in PD. In the Southern blot analysis, we could not find major deletions or insertions of mitochondrial DNA in PD. Our studies disclosed a differential mitochondrial impairment between PD and MM. We discuss the implication of our observation.
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PMID:Is Parkinson's disease a mitochondrial disorder? 157 31

To elicit possible variations in the CSF concentrations of copper, iron and manganese due to Parkinson disease (PD) or to the stage reached, we tested 11 patients with idiopathic PD, 6 untreated and 5 on long term L-dopa, versus 22 age and sex matched patients with other neurological disorders (control group-CG). The CSF levels of the three metals, measured by electrothermal atomization, did not differ significantly between the PD group and CG or between either of the PD subgroups and CG. Our findings therefore do not support the hypothesis that CSF Cu is a marker of PD.
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PMID:A case control study of CSF copper, iron and manganese in Parkinson disease. 162 80

Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.
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PMID:The threshold of pain and neurotransmitter's change on pain in Parkinson's disease. 170 99

Protracted long-term treatment of common marmosets with 15 doses (0.5-4.5 mg/kg, i.p.) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; total dose 25 mg/kg, given over 29 days) caused transitory changes in motor behaviour reminiscent of human Parkinson's disease. 16 days from the start of MPTP administration, all animals showed motor impairment, consisting of profound akinesia and a rigid posture, but in no case resting tremor. Biogenic amines were measured in nigrostriatal regions one month after finishing MPTP treatment. There was a profound loss of dopamine and serotonin in the substantia nigra and in the striatum; noradrenaline was only reduced in the putamen. Continuous analyses of the concentrations of biogenic amine metabolites in the CSF during this study revealed persistent dopaminergic disturbances and temporary alterations in serotoninergic and noradrenergic function.
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PMID:Neurochemical and behavioural features induced by chronic low dose treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset: implications for Parkinson's disease? 171 88

Dopaminergic neuron controls CNS functions such as meso-limbic, striato-nigral and tubero-infundibular systems. The purpose of the present study is the evaluation of the hypothalamic dopaminergic neuron activity in neuro-degenerative disorders. alpha-melanocyte-stimulating hormone (alpha-MSH) is synthesized in the arcuate nucleus and lateral part of the hypothalamus, and its secretion is under the inhibitory control of the dopaminergic neuron both in the hypothalamus and pituitary. alpha-MSH-like-immunoreactivity (alpha-MSH-LI) in CSF is thought to be representative to the dopaminergic neuron activity in the hypothalamus. We therefore evaluated CSF levels of alpha-MSH-LI in spinocerebellar degenerations and extrapyramidal diseases. The subjects are 11 patients with Parkinson's disease, 16 with Shy-Drager syndrome (SDS), 16 with cerebellar cortical atrophy, 3 with Machado-Joseph disease, 3 with dentato-rubro-pallido-luysian atrophy and 2 with Huntington's disease as well as 24 controls. All patients with Parkinson's disease were administered levodopa and carbidopa. CSF was sampled through lumbar puncture in the morning. After the centrifugation, supernatant of CSF was stored at -40 degrees C until used. alpha-MSH in CSF was extracted by Rainero's method and measured by RIA. alpha-MSH-LI levels in control was 23.9 +/- 2.6 pg/ml (mean +/- SD). The significant elevation was observed in Parkinson's disease (40.3 +/- 7.5, p less than 0.001) and SDS (42.3 +/- 9.4, p less than 0.001). The levels showed not significant correlation with age, duration of illness or severity of autonomic disorder. Most of other diseases demonstrated the levels within normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Abnormality of hypothalamic dopaminergic system in neuro-degenerative diseases--evaluation of alpha-melanocyte-stimulating hormone-like immunoreactivity in cerebrospinal fluid]. 176 56


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