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 free radical hypothesis for the pathogenesis of idiopathic parkinsonism (Parkinson's disease) has many similarities to the argument invoking an autoimmune mechanism. In both cases, cellular and molecular machinery that might be involved in neuronal destruction have been demonstrated. In recent years, the free radical hypothesis has become particularly fashionable; several workers have reported observations which, they infer, support the notion that damage by free radicals is a major factor in the underlying disease process. There is, however, no conclusive evidence that free radicals play a prominent role in the causal chain of events that leads to idiopathic parkinsonism; several findings may be construed as evidence against such a contention.
Ann Neurol 1992 Dec
PMID:The free radical hypothesis in idiopathic parkinsonism: evidence against it. 147 72

Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Ann Neurol 1992 Dec
PMID:The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. 147 73

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.
Clin Neuropharmacol 1992 Dec
PMID:The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease. 147 49

We studied the effect of chronic bromocriptine cotherapy on levodopa kinetics in seven patients with Parkinson's disease who were receiving levodopa therapy. Plasma levodopa concentrations were measured after a standard oral levodopa fasting dose over a 5-hour period, on two different sessions, without and with bromocriptine at a fixed daily dose of 15 mg. We found no statistically significant difference in the rate and extent of levodopa absorption between the two treatments, with minimal intrasubject variability. Our observations suggest that chronic bromocriptine cotherapy is unlikely to affect the plasma levodopa pharmacokinetics under standardized intake conditions or to contribute to a less predictable pattern of drug plasma concentrations.
Clin Neuropharmacol 1992 Dec
PMID:No effect of chronic bromocriptine therapy on levodopa pharmacokinetics in patients with Parkinson's disease. 147 50

The gene encoding the D2 dopamine receptor (DRD2) is located on human chromosome 11q23 and has been circumstantially associated with a number of human disorders including Parkinson's disease, schizophrenia, and susceptibility to alcoholism. To determine the physical structure of the DRD2 gene, we utilized cosmid cloning, isolation of yeast artificial chromosomes (YACs), and pulsed-field gel electrophoresis to construct a long-range physical map of human chromosome 11q23 linking the genes for the DRD2 and neural cell adhesion molecule (NCAM). The D2 dopamine receptor gene extends over 270 kb and includes an intron of approximately 250 kb separating the putative first exon from the exons encoding the receptor protein. The resulting physical map spans more than 1.5 mb of chromosome band 11q23 and links the DRD2 gene with the gene encoding the NCAM located 150 kb 3' of the DRD2 gene and transcribed from the same DNA strand. We additionally located the sites of at least four hypomethylated HTF islands within the physical map, which potentially indicate the sites of additional genes. High-resolution fluorescent in situ suppression hybridization using cosmid and YAC clones localized this gene cluster between the ApoAI and STMY loci at the interface of bands 11q22.3 and 11q23.1.
Genomics 1992 Dec
PMID:Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. 147 42

Parkinson's disease is a neurodegenerative disorder characterized mainly by a loss of the dopaminergic neurons of the nigrostriatal pathway. The symptomatic treatment, which consists of the supply of the deficient neurotransmitter dopamine, does not, however, prevent the progression of the disease and is frequently associated with major motor and psychiatric side effects. Recent basic and clinical investigations have led to the development of new therapeutical strategies for Parkinson's disease. The authors review and describe these new approaches which include: [1] treatments aimed at slowing down the progression of the disease, [2] treatments aimed at decreasing the motor side effects and [3] the use of intracerebral transplantations.
Rev Med Brux 1992 Dec
PMID:[Current therapeutic approach in Parkinson disease]. 148 Aug 87

Vascular pseudoparkinsonism may be confused with idiopathic Parkinson's disease. Patients may be unnecessarily treated with anti-parkinsonian drugs while their underlying vascular disease is ignored. We investigated 250 parkinsonian patients seen in our Movement Disorders Clinic for a possible vascular etiology. After excluding those with a known secondary cause such as drug-induced parkinsonism, progressive supranuclear palsy, multiple system atrophy and hyperparathyroidism, brain computed tomography and/or magnetic resonance imaging were performed on those who showed poor or no response to levodopa. In those with an ischemic lesion demonstrated on neuroimaging, anti-parkinsonian drugs were stopped and the patients were reassessed. Eleven patients (4.4%) had ischemic brain lesions accounting for their parkinsonism. All were initially diagnosed as Parkinson's disease because of the prominence of bradykinesia and rigidity. Gait disturbance was also common, but resting tremor was distinctly absent. Three anatomical patterns with different prognosis were identified. Three patients with basal ganglia lacunar infarct recovered spontaneously, three with frontal lobe infarcts remained static and five with periventricular and deep subcortical white matter lesions had progressive deterioration. Autopsy in one patient confirmed bilateral frontal lobe watershed infarcts and the absence of brain stem Lewy bodies. Parkinsonian patients with poor or no response to levodopa therapy should be investigated for a vascular etiology.
Acta Neurol Scand 1992 Dec
PMID:Vascular pseudoparkinsonism. 148 45

Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.
Acta Neurol Scand 1992 Dec
PMID:Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease. 148 46

Nutritional status was assessed in a group of patients with Parkinson's disease. Weight loss since the onset of disease occurred in 52% of the patients and 22% had lost more than 12.8 kg. Although 67% of patients experienced eating difficulties of some kind, dietary intakes of protein and energy were not significantly lower than recommended intakes. Plasma levels of albumin (44.2 g/l vs 45.7 g/l), vitamin A (2.61 vs 2.94 mumol/l), vitamin E (22.0 vs 32.0 mumol/l), iron (15.3 vs 18.3 mumol/l) and zinc (14.2 vs 18.7 mumol/l) were significantly lower (P < 0.05) in the patients than in healthy controls. Levels of ferritin, total iron-binding capacity and copper were similar between groups. The potential significance of low levels of vitamin E and zinc are discussed in relation to oxidative stress in the pathogenesis of this disease.
Eur J Clin Nutr 1992 Dec
PMID:Diet, body size and micronutrient status in Parkinson's disease. 148 17

In vitro, iris contractions after muscarinic agonists were measured in mg of tension change and the concentration producing 50% of the response was expressed as EC50 mumol/l. Although the average EC50 value of carbachol in the iris sphincter of the donors with diabetes or Parkinson's disease did not change significantly when compared with the control, the maximum contraction of the tissue from the diseased state was increased significantly. Thus, in addition to the well known denervation supersensitivity of the iris-dilator, the iris-sphincter also develops adaptive sensitivity changes. Antimuscarinic drug treatment in some Parkinson's patients interfered with the estimation of supersensitivity in vitro studies. The enhanced response of carbachol at the low temperatures or the relative potency of carbachol and pilocarpine in the tissue obtained from the diseased donors was not significantly different from that of controls. Based on EC50 values, the potency of arecoline on the iris was 1/3 that of carbachol. Significantly lower EC50 values of carbachol were found in irides which were in contact with open loop type anterior chamber lens implants compared with those in contact with the closed loop anterior chamber lens implants. Maximum responses of irides to carbachol were less when the tissue was in contact with open loop lens compared with those in contact with closed loop anterior chamber implants. Irides from many donors having unilateral or bilateral replacement of the artificial lenses responded with EC50 of carbachol which was approximately equal to that of the contralateral eye. The maximum difference between EC50 values of the left and right iris was less than 5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)
Naunyn Schmiedebergs Arch Pharmacol 1992 Dec
PMID:Cholinergic sensitivity of irides from donors with various pathological conditions and lens implants. 148 63


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