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)

Marked, disabling fluctuations in motor performance (on-off phenomena) appear after chronic L-Dopa therapy in Parkinson's disease (PD). Intravenous infusion of L-Dopa greatly reduces these motor fluctuations, but it is not reliable as a chronic treatment. Therefore, infusion of the potent, water-soluble dopaminergic agonist lisuride has been tested. However, many patients did not respond to infusion of lisuride alone, and no clinical parameter is known to correlate with the lacking response. In order to study this problem, we performed the TRH test (200 micrograms i.v.) in 8 PD patients with severe motor fluctuations; before and during lisuride subcutaneous infusion, we measured PRL and TSH responses to TRH. Both PRL and TSH receive an inhibitory control from dopaminergic receptors on pituitary cells, whereas they are stimulated by TRH. The TRH test, given during lisuride infusion, allows an indirect evaluation of the 'brake function' of the dopaminergic system on anterior pituitary, i.e. of dopaminergic receptor sensitivity in vivo. In our study, TRH induced a significant TSH rise in all PD patients, before and during lisuride infusion. Moreover, the lisuride responders (i.e. patients showing constant 'on' period during lisuride infusion, 4 patients) showed a significant lower TSH response as compared to nonresponders. PRL levels followed the same trend without reaching statistical significance. These data are compatible with the presence, in the two groups, of a different pituitary dopaminergic sensitivity which would suggest the presence of pharmacodynamic factors associated with the lacking response to intravenous lisuride infusion.
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PMID:TRH test and the continuous dopaminergic stimulation in complicated Parkinson's disease. 156 63

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedating the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.
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PMID:Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area. 158 37

The study investigated features of life-style and dietary habits early and late in life of patients with idiopathic Parkinson's disease (IPD). Seventy-one patients and 103 controls were interviewed personally with a structured questionnaire. Living in villages during primary school time was significantly more frequent among patients, and in the urban environment patients had lived less frequently in larger-sized towns. Mushroom harvesting during childhood was more frequent among patients. No difference between patients and controls was found in childhood water supply, habits of fishing in the countryside or at the seaside, and eating such fish. Actual food preference in patients was greater for almonds and plums, while no difference was found in the actual intake of mushrooms, peanuts, oil-dressed salad, fish and animal offals. The study did not indicate a higher consumption of foods known to harbour heavy metals and pesticides in IPD patients either long before or during the disease. Reduced consumption of foodstuffs rich in vitamin E, as reported previously for premorbid patients, is no longer observed in patients with overt disease.
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PMID:Life-style and dietary factors early and late in Parkinson's disease. 162 41

The distribution and level of labeling for the messenger RNA encoding preprosomatostatin was studied in the striatum and entopeduncular nucleus of rats with and without a selective destruction of the dopaminergic nigrostriatal pathway. 6-Hydroxydopamine was injected unilaterally in the substantia nigra and the animals were killed 2 or 3 weeks after the lesion. Preprosomatostatin messenger RNA was visualized with a 35S-labeled RNA or DNA probe in frontal cryostat-cut sections by in situ hybridization histochemistry. The number of labeled cells as well as the intensity of labeling overlying each cell were measured on radioautograms developed before saturation of the emulsion. In rats with a 6-hydroxydopamine lesion, the number of labeled cells and the intensity of labeling over each cell were decreased in the striatum ipsilateral to the lesion compared to the contralateral side and to both striata of control rats. In the same sections, the number of cells in the cerebral cortex was lower in the ipsilateral side of the lesion but the difference was only significant in the frontoparietal cortex. In contrast, a massive increase (+300%) in the number of labeled cells and in the intensity of labeling per cell was observed in the entopeduncular nucleus and the adjacent lateral hypothalamus on the side ipsilateral to the lesion when compared to the contralateral side and to control rats. The results suggest that dopamine exerts opposite effects on somatostatin gene expression in neurons of the striatum and the entopeduncular nucleus/lateral hypothalamus, effects which are likely to be of importance for the control of basal ganglia output activity. In addition, the dramatic changes observed in the somatostatinergic neurons of the lateral hypothalamus, an area involved in the control of food and water intake, may be related to some aspects of the symptomatology of Parkinson's disease.
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PMID:Lesions of the dopaminergic nigrostriatal pathway alter preprosomatostatin messenger RNA levels in the striatum, the entopeduncular nucleus and the lateral hypothalamus of the rat. 167 45

Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self-administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study.
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PMID:A pilot study of occupational and environmental risk factors for Parkinson's disease. 174 30

The Eighth International Neurotoxicology Conference, Role of Toxicants in Neurological Disorders (1990), evaluated the evidence that chemical exposures may play a role in the development of neurodegenerative disorders. This article describes the major neurodegenerative disorders (Amyotrophic Lateral Sclerosis, Huntington disease, Parkinson disease, and Alzheimer disease) addressed at the conference, followed by a description of test systems or models developed to study behavioral aspects of these disorders in animals. However, due to the complexity of the disorders and the species in which they are found, fully-developed models in animals of neurodegenerative disorders are lacking. This suggests the need for a clear strategy for selecting behavioral tests in animals to study aspects of any neurodegenerative disorders. Such a strategy is here exemplified for Alzheimer disease (AD) as a prototypical neurodegenerative disorder. Since an animal model cannot provide the full range of effects of human neurodegenerative diseases, particularly AD which produces incompletely characterized cognitive deficits, a rodent model must at this time be drawn from multiple sources, including: (1) Tests currently used to identify in rodents deficits associated with AD; (2) tests to identify Alzheimer-related signs in patients; and, (3) tests that relate to theoretical constructs of human and animal cognition. A battery that draws from those sources could include tests of: (a) Spatial learning and memory (Morris Water Maze and Radial Arm Maze), (b) delayed recall match-to-sample; (c) serial response learning; and, (d) visual discrimination (e.g., vertical vs. horizontal stimuli). This battery will identify behavioral changes characteristic of early-, middle- and late-stage AD, afford the potential to relate the findings to theoretical constructs of cognition, and evaluate learning capabilities not previously studied in rodent models of neurodegenerative disorders.
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PMID:Animal test systems to study behavioral dysfunctions of neurodegenerative disorders. 174 32

The etiology of the nigrostriatal pathway degeneration in Parkinson's disease (PD) is unknown but there is a growing pool of evidence that environmental factors may be involved in the genesis of this disorder. The discovery of the N-Methyl 4-Phenyl 1,2,3,6-Tetrahydro-Pyridine (MPTP)-induced injury in late 1970s provided the first experimental model of PD and stimulated dramatically the epidemiological research. An excitotoxic amino acid contained in Cycadales, which is thought to be responsible for the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, provides another example of toxin-induced parkinsonism. This amino acid is present in most seeds common in the Western diet. In developed countries, prevalence of PD is 2 to 5 times as high than in developing countries. PD patients in developed countries are more likely than controls to have lived in rural environment. Case control studies have suggested that this positive association is possibly related to pesticides and herbicides exposures or well water drinking. Dietary surveys are now going on and several hypothesis are tested including high MPTP-structural analogs or seeds consumption in PD patients and low antioxidants consumption. The negative association between smoking habits and PD has been recognized for more than 20 years. There is evidence that this association is not an artefact due to the disease affecting smoking habits. Its origin is unknown but it could provide important aetiological clues for PD. The most recent hypothesis concerning the relationships between these environmental factors and PD are reviewed and pertinent suitable surveys for the future are discussed.
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PMID:[Parkinson's disease and environmental factors]. 175 3

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
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PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

To determine whether a history of exposure to rural environmental factors leads to an increased likelihood of developing idiopathic Parkinson's disease, we conducted a case-control study of 130 cases and 260 randomly selected community controls (matched with the cases by sex and age +/- 2.5 years at a ratio of 2 controls: 1 case) in the city of Calgary. The data were collected by personal interviews and were analyzed using conditional logistic regression for matched sets. The ages of the cases ranged from 36.5 to 90.7 years (mean = 68.5 +/- 11.3 years). The mean age at diagnosis was 61.1 +/- 12.4 years. The mean duration of disease was 7.8 +/- 0.6 years. Eleven (9.1%) cases were diagnosed before age 40. In this sample from the Province of Alberta, Canada, no significant increase in risk for Parkinson's disease was associated with a history of rural living, farm living, or well water drinking in early childhood or at any time during the first 45 years of life.
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PMID:Parkinson's disease and exposure to rural environmental factors: a population based case-control study. 191 61

The motor deficits associated with Parkinson's disease may be ameliorated by intrastriatal placement of dopamine-secreting cells in a polymer capsule. Water soluble polyelectrolytes were utilized for membrane encapsulation of dopamine-secreting PC12 cells. Membrane permeability studies revealed exclusion of radiolabeled 69,000 Da albumin, whereas 30,000 Da carbonic anhydrase was able to cross the membrane. No cytolytic activity was observed following incubation of the encapsulated PC12 cells with PC12 cell-directed antiserum and fresh complement. In vitro, dopamine release and the surface area of intact cells per microcapsule, reached a plateau at 4 weeks that was maintained for at least 12 weeks. Viable PC12 cells were observed in microcapsules implanted for 4 and 8 weeks in nonlesioned guinea pig striata. The behavioral effect of intrastriatal dopamine release from microencapsulated PC12 cells was evaluated in the 6-hydroxydopamine unilaterally lesioned rat model. From 1 to 4 weeks postimplantation a significant reduction in rotation behavior under apomorphine challenge was observed with PC12 cell-loaded microcapsules as compared to empty microcapsules. Tyrosine hydroxylase immunopositive PC12 cells were observed 4 weeks postimplantation in all animals exhibiting a reduction in turning behavior. Implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters and growth factors to the nervous system.
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PMID:Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells. 191 23


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