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)

Renal handling of urate, xanthine and hypoxanthine was studied in a hypouricemic patient who had increased plasma concentrations of xanthine and hypoxanthine. The patient, a 50-year-old man, had been suffering from Parkinson's disease, while neither systemic disorders nor particular renal diseases known to affect plasma purine levels were found. His serum urate level was 58 +/- 6 mumol/l (healthy controls for males, 310 +/- 48 mumol/l, mean +/- SD) and the renal uric acid clearance was 3 times higher than that of the controls, establishing a diagnosis of renal hypouricemia. Xanthine and hypoxanthine concentrations in the plasma were elevated to 1.3 +/- 0.1 mumol/l (controls, 0.5 +/- 0.3) and 5.9 +/- 3.5 mumol/l (controls, 1.6 +/- 0.4), respectively. Both renal xanthine and hypoxanthine clearance was only half the value of the controls, indicating reduced urinary excretion of xanthine, and hypoxanthine appears to be responsible for their elevation in plasma. A probenecid loading test revealed no response of urinary urate excretion but normal responses of xanthine and hypoxanthine excretion. However, urinary excretion of urate, xanthine or hypoxanthine did not respond at all to pyrazinamide administration. These findings indicate that the patient had a defective renal handling of xanthine and hypoxanthine as well as urate.
Nephron 1992
PMID:Decreased renal clearance of xanthine and hypoxanthine in a patient with renal hypouricemia: a new defect in renal handling of purines. 150 40

Male retired breeder C57/Bl and CD-1 mice were treated with either MPTP or its vehicle. At 7-10 days post-treatment, catecholamine concentrations within the olfactory bulbs (OB) and hypothalamus were determined. Norepinephrine concentrations within the OB were significantly decreased in MPTP-treated mice. These effects were more pronounced in the CD-1 (50% reduction) compared to the C57/Bl (20% reduction) strain. No effects of MPTP were observed on norepinephrine concentrations within the hypothalamus. Dopamine concentrations in the OB and hypothalamus did not differ between MPTP- and vehicle-treated mice in either strain. Overall, catecholamine concentrations within the OB, but not the hypothalamus, were significantly greater in C57/Bl compared to CD-1 mice. The reduction in OB norepinephrine concentration in the MPTP-treated animals may be related to the olfactory deficits which accompany Parkinson's disease.
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PMID:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces norepinephrine concentrations in the olfactory bulbs of male mice. 151 43

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.
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PMID:Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats. 176 Jul 45

The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed.
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PMID:Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats. 190 4

The Parkinson-syndrome is the most important syndrome under the extrapyramidal disease. The therapy with L-DOPA has a prominent place in the therapy of Parkinson disease since the introduction of oral effective drugs. Dopamin has an effect to the basalganglia as a neurotransmitter and perhaps an inhibition effect to specific synapses of brain. The inhibition or the optimal balance of the cholinergic systems is the effect of Dopamin and Noradrenalin. The therapy with low dosis of L-DOPA in combination with a decarboxylase-inhibitor will be prevent the side-effects of nerv-cells.
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PMID:[Thoughts on the neurobiological aspects of Parkinson syndrome]. 301 Mar 57

Norepinephrine was measured in postmortem cerebellar cortex of 22 non-neurological control subjects and nine patients with Parkinson's disease, using the high-performance liquid chromatography method with amperometric detection. In all control subjects, substantial amounts of norepinephrine was found in cerebellar cortex. There was a moderate negative correlation between age of control subjects and cerebellar norepinephrine concentration. In the patients with Parkinson's disease, the cerebellar cortical norepinephrine levels were significantly below normal. This is in accord with previously reported reduced norepinephrine levels in locus ceruleus and other regions of the parkinsonian brain. Although the main symptoms of Parkinson's disease are primarily caused by disturbed basal ganglia (dopamine) function, cerebellar dysfunction related to norepinephrine may contribute to some abnormalities of motor performance in this disorder.
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PMID:Cerebellar norepinephrine in patients with Parkinson's disease and control subjects. 672 35

The major symptoms of Parkinson's disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal dopaminergic terminals. Norepinephrine, serotonin, and melanin pigments are also decreased and cholinergic activity is increased. The cause of PD is unknown. Increased methylation reactions may play a role in the etiology of PD, because it has been observed recently that the CNS administration of S-adenosyl-L-methionine (SAM), the methyl donor, caused tremors, hypokinesia, and rigidity; symptoms that resemble those that occur in PD. Furthermore, many of the biochemical changes seen in PD resemble changes that could occur if SAM-dependent methylation reactions are increased in the brain, and interestingly, L-DOPA, the most effective drug used to treat PD, reacts avidly with SAM. So methylation may be important in PD; an idea that is of particular interest because methylation reactions increase in aging, the symptoms of PD are strikingly similar to the neurological and functional changes seen in advanced aging, and PD is age-related. For methylation to be regarded as important in PD it means that, along with its biochemical reactions and behavioral effects, increased methylation should also cause specific neuronal degeneration. To know this, the effects of an increase in methylation in the brain were studied by injecting SAM into the lateral ventricle of rats. The injection of SAM caused neuronal degeneration, noted by a loss of neurons, gliosis, and increased silver reactive fibers in the SN. The degeneration was accompanied with a decrease in SN tyrosine hydroxylase (TH) immunoreactivity, and degeneration of TH-containing fibers. At the injection site in the lateral ventricle it appears that SAM caused a weakening or dissolution of the intercellular substances; observed as a disruption of the ependymal cell layer and the adjacent caudate tissues. SAM may also cause brain atrophy; evidenced by the dilation of the cerebral ventricle. Most of the SAM-induced anatomical changes that were observed in the rat model are similar to the changes that occur in PD, which further support a role of SAM-dependent increased methylation in PD.
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PMID:Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. 788 91

In order to estimate the role of the sympatho-adrenal system as a trigger in cardiovascular mortality risk after L-DOPA administration in patients with Parkinsons disease we performed the following experiments in normotensive Wistar-Kyoto-rats (WKY) and spontaneously hypertensive rats (SHR). L-DOPA was given orally in increasing doses (30, 100, 300 mg/kg b.w.). Haemodynamic parameters (BP, HR) were measured by tail cuff plethysmography and catecholamine concentrations in tissues assayed by high pressure liquid chromatography. Stressful situations were induced by experimental myocardial infarction. After administration of L-DOPA a dose-dependent increase in blood pressure in both WKY and SHR was observed with a prolongation in SHR. Significantly increased concentrations of dopamine in the hearts were measured in both strains. Noradrenaline stores in the heart of WKY were more filled than in the heart of SHR. Only in SHR high adrenaline concentration in the adrenal medulla were measured after L-DOPA administration. Circulating adrenaline concentrations were significantly enhanced after myocardial infarction in WKY and could be further elevated by pretreatment with L-DOPA. From the results obtained it is concluded that L-DOPA administration in WKY and SHR leads to exaggerate synthesis and massive release of catecholamines and in consequence to an enhanced cardiovascular mortality risk due to cardiotoxicity of catecholamines. It can be extrapolated that increased cardiovascular mortality risk seen in Parkinson patients treated with L-DOPA and benzerazide is probably associated with increased synthesis and release of catecholamines during stressful situations.
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PMID:Cardiotoxicity of catecholamines after application of L-DOPA in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 852 51

The major symptoms of Parkinson disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by the degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal DA terminals. Norepinephrine (NE) and serotonin (5-HT) levels in the neostriatum and tyrosine hydroxylase and melanin pigments in the substantia nigra are also decreased, and brain cholinergic activity is increased. The cause of PD is unknown, but PD is an age-related disorder, suggesting that changes that occur during the aging process may help to precipitate PD. Methylation increases in aging animals. Increased methylation can deplete DA, NE, and 5-HT; increase acetylcholine; and cause hypokinesia and tremors. These effects are similar to changes seen in PD, and interestingly also, they are similar to some of the changes that are associated with the aging process. It is suggested, therefore, that increased methylation may be an inducing factor in parkinsonism. Accordingly, the effects of an increase in methylation in the brain of rats were studied. S-adenosylmethionine (AdoMet), the limiting factor in the methylation process, was injected into the lateral ventricle of rats. Specific behavioral changes that resemble changes seen in PD were investigated. The results showed that AdoMet caused tremors, rigidity, hypokinesia, and depleted DA. The hypokinetic effects of a single dose of AdoMet lasted for about 90 min. AdoMet has a dose-dependent hypokinetic effect. A dose of 9.4 nmol reduced movement time (MT) by 68.9% and increased rest time (RT) by 20.7%, and a dose of 400 nmol reduced MT by 92.4% and increased RT by 27.6%. The normethyl analog of AdoMet, S-adenosylhomocysteine, did not cause hypokinesia or tremors, but it blocked the AdoMet-induced motor effects. L-dopa, the precursor of DA, also blocked the AdoMet-induced motor effects. These data suggest that the methyl group of AdoMet as well as DA depletion are involved in the AdoMet-induced motor effects. A dose of 0.65 mumol of AdoMet depleted DA in the ipsilateral caudate nucleus (CN) or neostriatum by 50.1%, and DA in the contralateral CN was reduced by 9.3%. Double the dose of AdoMet did not increase the depletion of DA on the ipsilateral CN, but DA in the contralateral CN was decreased by 26.3%. Taken together, the results suggest that increased methylation may contribute to the symptoms of PD.
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PMID:Striatal dopamine depletion, tremors, and hypokinesia following the intracranial injection of S-adenosylmethionine: a possible role of hypermethylation in parkinsonism. 874 29

Treatment of Parkinson's disease with L-dopa is plagued in a majority of patients by dyskinesias. Noradrenaline/dopamine interactions are proposed on behavioral, biochemical, physiological and anatomical grounds. The aim of the study was to test the potential antidyskinetic effect of the alpha2-adrenoceptor antagonist, idazoxan, in a primate model of Parkinson's disease. Six female cynomolgus monkeys previously rendered parkinsonian by the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and presenting an unchanged syndrome for several months were used. All responded readily to L-dopa but had developed dyskinesias which were manifested with each dose. In the first part of the study, seven doses of idazoxan (ranging from 0.25 mg/kg to 10 mg/kg, p.o.) were administered together with the vehicle or in combination with a fixed dose of L-dopa/benserazide (100/25 mg, p.o.). In the second part of the study, a fixed dose of idazoxan (7.5 mg/kg) was administered daily for 10 days and L-dopa was added to idazoxan on days 1, 4, 7 and 10. Vehicle (empty capsule) was used as control. Idazoxan, by itself (ranging from 5 mg/kg to 10 mg/kg), increased locomotor activity and improved the disability score with virtually no dyskinesias in three animals. In combination with L-dopa, idazoxan did not impair the antiparkinsonian response but significantly reduced dyskinesias in all six animals up to 65% at doses of 7.5 mg/kg and 10 mg/kg and delayed their onset, so that the "ON" state without dyskinesias was prolonged. The antidyskinetic effect of idazoxan was maintained when repeatedly administered for 10 days. On day 10, the locomotor response to L-dopa was significantly potentiated by chronic administration of idazoxan. Our results indicate that idazoxan has some antiparkinsonian effect of its own and may constitute a useful adjunct to L-dopa as it can reduce dyskinesias without impairing the relief of symptoms, this effect being maintained over time in this model.
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PMID:Noradrenoceptor antagonism with idazoxan improves L-dopa-induced dyskinesias in MPTP monkeys. 1068 74


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