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)

We have studied the urinary excretion of 1,4-methylhistamine (1,4-MeHm), 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in patients with Parkinson's disease, choreiform movements and essential tremor. The effect of amantadine on urinary excretion has been measured in each group of patients as well as the effect of levodopa in patients with Parkinson's disease. In patients with Parkinson's disease, excretion of 1,4-MeHm and HVA was significantly lower than in controls. Patients with choreiform movements had a reduced excretion of HVA but trends toward low levels of 1,4-MeHm and, in patients with Huntington's chorea, elevated excretion of 5-HIAA, were not significant. In patients with essential tremor, urinary excretion of the amine metabolities studied did nof differ significantly from controls. Administration of amantadine to patients with Parkinson's disease was not followed by increased excretion of monoamine metabolites except in those patients who were already receiving anticholinergic drugs. This increase is not significant and there was no effect in other groups of patients. These findings lend no support to the view that amantadine has a general amine-releasing action although there is limited evidence for such an effect in Parkinson's disease. In addition to the expected increase in HVA excretion, administration of levodopa to Parkinsonian patients was followed by significantly reduced excretion of 1,4-MeHm and 5-HIAA. However, if amantadine and levodopa were given together, excretion of 5-HIAA was still reduced, but that of 1,4-MeHm was normal. Levodopa may thus modify the turnover of histamine, which appears to be reduced in Parkinson's disease, and this effect may be modified by amantadine.
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PMID:Urinary monoamine metabolite excretion in disorders of movement. Effects of amantadine and levodopa. 87 21

The relationship between dopamine receptor activation and the relief of parkinsonian clinical features was studied in 40 patients with Parkinson's disease. Treatment with dopamine receptor agonists, piribedil or bromocriptine, decreased significantly both the basal level and probenecid-induced accumulations of homovanillic acid (HVA) in the CSF. But there were no changes in the concentrations of 5-hydroxyindole acetic acid (5-HIAA). Correlation analyses showed that patients who improved with both the dopamine agonists used had significantly lower probenecid response of HVA in the CSF and a less severe disease condition than those without beneficial effect. This relationship between dopamine receptor activation and improvement of parkinsonian disability suggests that the therapeutic efficacy of dopamine receptor agonists depends on the functional capacity of brain dopaminergic mechanisms.
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PMID:Brain dopamine turnover and the relief of parkinsonism. 90 36

To estimate the effect of long-term administration of L-3,4-dihydroxyphenylalanine (L-Dopa) on methylation of compounds not formed from it, the urinary excretion of histamine and its methylated metabolites was studied in rats and guinea pigs fed L-Dopa in their diets and in patients with Parkinson's disease being treated with L-Dopa. In the guinea pigs, but not in the rats, L-Dopa administration decreases excretion of histamine and of its methylated metabolites, methylhistamine and 1-methylimidazole-4-acetic acid. Because excretion of 1-methylimidazole-5-acetic acid, which comes from the diet and is not a metabolite of histamine, was unaffected by the L-Dopa treatment, the decreases were due to a specific effect of L-Dopa on histamine metabolism. When compared to normal control subjects, patients with Parkinson's disease excreted less histamine and methylhistamine, both before and during treatment with L-Dopa. Administration of the peripheral aromatic L-amino acid decarboxylase inhibitor, L-alpha-methyldopa hydrazine (MK 486), decreased urinary excretion of histamine markedly. Neither L-Dopa nor MK 486 appeared to influence excretion of the imidazoleacetic acids in the patients. The results suggest that L-Dopa may decrease histamine formation or release in some species but that it does not influence histamine methylation.
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PMID:Effect of L-DOPA on endogenous histamine metabolism. 115 52

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

In cerebrospinal fluid, levels of the histamine metabolites, tele-methylhistamine and tele-methylimidazole-acetic acid, were higher in elderly than in young people, and women had higher levels than men. Therefore, age and gender should be considered in studies of histamine metabolites as exemplified by their measurements in cerebrospinal fluid of patients with Huntington's disease. Levels of pros-methylimidazoleacetic acid, an isomer of tele-methylimidazoleacetic acid and not a metabolite of histamine, were higher in cerebrospinal fluid of men than of women. Levels of pros-methylimidazoleacetic acid in cerebrospinal fluid were highly positively correlated with the severity of Parkinson's disease in a group of non-medicated, mildly to moderately affected patients.
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PMID:Histamine metabolites and pros-methylimidazoleacetic acid in human cerebrospinal fluid. 182 34

We have compared hypothalamic contents of various neurotransmitters (dopamine (DA), norepinephrine and serotonin) and their metabolites (dihydroxyphenyl acetic acid, homovanilic acid, 5-hydroxyindoleacetic acid) in post-mortem human controls and parkinsonian hypothalami. Neurotransmitters and their metabolites were measured in 0.1 N HCl hypothalami extracts using electrochemical detection after high performance liquid chromatography. Using specific radioimmunoassays we have also measured corticoliberin and somatocrinin contents in these hypothalami. Despite a 50% decrease of DA contents in parkinsonian hypothalami, no variations of corticoliberin and somatocrinin contents were found: 16.6 +/- 1.78 pg/mg tissue in Parkinson disease vs 16.71 +/- 1.89 in controls for human corticotropin-releasing factor (hCRF 1-41) and 37.38 +/- 11 vs 45.16 for human growth-hormone-releasing factor (hGRF 1-44).
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PMID:Corticoliberin, somatocrinin and amine contents in normal and parkinsonian human hypothalamus. 240 85

Two patients with Parkinson's disease were treated with 1 g tetrahydrobiopterin (BH4) for 5 days. Clinical improvement was not observed. In the cerebrospinal fluid (CSF) a 4-8 fold increase in the concentration of homovanillic acid (HVA), and a 3-fold increase in the concentration of 5-hydroxyindole acetic acid (5-HIAA) was measured. However, the concentration of HVA reached, was only approximately half as high, as that of patients treated with madopar (DOPA + benserazid). In urine, the excretion of HVA increased 13-37 fold, when the patients were treated with madopar, whereas no increase in the HVA excretion was measured after the BH4 administration. Additionally, 2 patients with Parkinson's disease were treated with 1 g BH4 in combination with 15 g tyrosine for 3 days, and 1 parkinsonian patient was treated with 15 g tyrosine daily for 7 weeks. No increase in the CSF concentrations of HVA or 5-HIAA was observed. The results suggest, the BH4 in the dosage used, is not effective in the treatment of Parkinson's disease.
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PMID:Tetrahydrobiopterin and Parkinson's disease. 247 6

We investigated the effect of systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine (gamma-Glu-DOPA) on catecholamine contents in the brain. gamma-Glu-DOPA was transformed to dopamine (DA) in vitro with brain homogenate by the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase. Intraperitoneal injection of gamma-Glu-DOPA to mice increased DA markedly and noradrenaline (NA) moderately in the brain. The increase of endogenous DA was followed by elevation of the main DA metabolites (3,4-dihydroxyphenyl-acetic acid and homovanillic acid). These increases were in a dose-dependent manner. The maximal elevation of DA was observed within 30 min after administration of gamma-Glu-DOPA, but a substantial increase of NA was observed 2 h after the administration. These results suggest that gamma-Glu-DOPA may be applicable to the treatment of Parkinson's disease.
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PMID:Increase of catecholamines in mouse brain by systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine. 311 8

The distribution of vasoactive intestinal peptide (VIP) in the post-mortem human brain was determined by radioimmunoassay using a highly specific antiserum. The detection limit of the assay was 4 fmol/tube. The highest concentrations of VIP were found in the cerebral cortex, amygdala, hypothalamus and hippocampus. The lowest levels of peptide were detected in basal ganglia including caudate nucleus, external pallidum, putamen and substantia nigra. All dilution curves of acetic acid extracts from different brain areas were strictly parallel to the standard curve. Sephadex G-50 gel filtration of frontal cortex extract showed that VIP-like immunoreactivity (VIP-LI) eluted as a major peak comigrating with synthetic hVIP. Detailed mapping of VIP in the human cerebral cortex showed the existence of a rostro-caudal gradient of VIP-LI concentrations: the frontal cortex exhibited the highest VIP levels, the parietal and temporal cortex contained medium values and the occipital cortex contained the lowest VIP levels. The concentrations of VIP-LI were compared in various regions of the human brain from normal and parkinsonian subjects. No significant changes in VIP-LI levels occurred in the brains of patients dying with Parkinson's disease. No difference in VIP levels could be found either when the parkinsonian group was subdivided into nondemented and demented patients. These data indicate that VIP-containing neurons are not affected in parkinsonian patients. Our results also suggest that VIP neuronal systems are not involved in the course of dementing process in Parkinson's disease.
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PMID:Regional distribution of vasoactive intestinal peptide in brains from normal and parkinsonian subjects. 322 55

Both fresh and cryopreserved-thawed human fetal ventral mesencephalon have been used for preclinical research and implantation into the brains of patients with Parkinson's disease. Further characterization and an evaluation of the effects of cryopreservation on immunocytochemical and neurochemical markers of monoamine neurons in human fetal ventral mesencephalic tissue are reported here. Fresh and cryopreserved-thawed human fetal mesencephalic tissue of 7-10 weeks fetal age was analyzed for the presence of tyrosine hydroxylase-like immunoreactivity and levels of dopamine (DA), norepinephrine, serotonin, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid. After fixation, cryopreserved-thawed mesencephalic tissue exhibited cellular tyrosine hydroxylase-like immunoreactivity identical to that seen in fresh tissue. The levels of DA, norepinephrine, serotonin, and 5-hydroxyindole acetic acid in the cryopreserved-thawed tissue were the same as the levels in fresh tissue. The levels of DOPAC were higher, and those of HVA were lower, in the cryopreserved-thawed tissue compared to the levels in fresh tissue. The changes in the levels of the DA metabolites, DOPAC and HVA, without corresponding change in the levels of the parent monoamine in cryopreserved-thawed tissue, indicate ongoing metabolic activity in DA-containing neurons. These results further suggest that cryopreservation and subsequent thawing does not have a measurable adverse effect on DA biosynthesis in the human fetal mesencephalon. The presence of the monoamines and their metabolites in the ventral mesencephalon at 7-10 weeks of fetal age coincides well with the early presence of immunocytochemical markers of monoamine neurons and reflects the early function of the nuclear groups containing specific monoamine neurotransmitters.
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PMID:Tyrosine hydroxylase immunoreactivity and monoamine and metabolite levels in cryopreserved human fetal ventral mesencephalon. 768 60


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