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)

Environmental risk factors were examined using univariate and multivariate unconditional logistic regression models in 89 nondemented patients with Parkinson's disease (PD) and 188 control subjects in a multiethnic urban community. Rural living, area farming, and drinking well water were associated with PD only in African-Americans. In Hispanics, area farming was protective, whereas drinking unfiltered water was a risk factor for PD. Consideration of ethnic and cultural origin may add to the epidemiologic study of PD.
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PMID:Environmental risk factors for Parkinson's disease in an urban multiethnic community. 944 93

Electroconvulsive therapy (ECT) is an efficacious treatment for a variety of neuropsychiatric conditions including major depression, mania, catatonia, Parkinson's disease, and neuroleptic malignant syndrome. However, ECT-induced memory dysfunction complicates the treatment and is a major concern for both patients and providers. We briefly review ECT-induced memory dysfunction and propose a glutamatergic model for it. (Articles examined were retrieved by a Medline search on the terms electroconvulsion and glutamate, with language limited to English.) Specifically, we hypothesize that ECT-induced memory dysfunction results from neuronal insults due to excessive release of excitatory amino acids and activation of their receptors, which produce cation and water flux and reversible oxidative stress. This model offers multiple testable hypotheses; exploring them may help to identify the risk factors for this significant side effect of ECT treatment and may thus yield effective agents for its prevention and treatment.
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PMID:A glutamatergic model of ECT-induced memory dysfunction. 955 49

We assessed exposure to pesticides, farming, well water use, and rural living as risk factors for Parkinson's disease (PD) in a population-based case-control study consisting of men and women > or = 50 years of age who had primary medical care at Henry Ford Health System in metropolitan Detroit. Enrolled PD patients (n = 144) and control subjects (n = 464) were frequency-matched for age, race, and sex. When adjusted for these variables and smoking status, there was a significant association of occupational exposure to herbicides (odds ratio [OR], 4.10; 95% CI, 1.37, 12.24) and insecticides (OR, 3.55; 95% CI, 1.75, 7.18) with PD, but no relation was found with fungicide exposure. Farming as an occupation was significantly associated with PD (OR, 2.79; 95% CI, 1.03, 7.55), but there was no increased risk of the disease with rural or farm residence or well water use. The association of occupational exposure to herbicides or insecticides with PD remained after adjustment for farming. The association of farming with PD was maintained after adjustment for occupational herbicide exposure and was of borderline significance after adjustment for occupational insecticide exposure. These results suggest that PD is associated with occupational exposure to herbicides and insecticides and to farming and that the risk of farming cannot be accounted for by pesticide exposure alone.
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PMID:The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living. 959 85

Motor effects mediated through adenosine A2A receptors within the caudate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 microg in 1 microl per side), a water-soluble phosphate prodrug of the selective A2A receptor antagonist MSX-2. Blockade of striatal A2A receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by systemic dopamine D1 (0.75 mg/kg SCH23390, i.p.) or dopamine D2 receptor blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A2A receptors within the caudate-putamen are tonically activated by endogenous adenosine and that a striatal A2A receptor blockade produces motor stimulant effects, in particular in animals with dopamine hypofunction. The present results support the view that A2A receptor antagonists may be potentially useful therapeutics for the treatment of Parkinson's disease.
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PMID:Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen. 966 4

The potential of most N-methyl-D-aspartate antagonists as neuroprotectants is limited by side effects. We previously reported that memantine is an open-channel N-methyl-D-aspartate blocker with a faster off-rate than many uncompetitive N-methyl-D-aspartate antagonists such as dizocilpine maleate. This parameter correlated with memantine's known clinical tolerability in humans with Parkinson's disease. Memantine is the only N-methyl-D-aspartate antagonist that has been used clinically for excitotoxic disorders at neuroprotective doses. Therefore, we wanted to investigate further the basis of its clinical efficacy, safety, and tolerability. Here we show for the first time for any clinically-tolerated N-methyl-D-aspartate antagonist that memantine significantly reduces infarct size when administered up to 2 h after induction of hypoxia/ischemia in immature and adult rats. We found that at neuroprotective concentrations memantine results in few adverse side effects. Compared to dizocilpine maleate, memantine displayed virtually no effects on Morris water maze performance or on neuronal vacuolation. At concentrations similar to those in brain following clinical administration, memantine (6-10 microM) did not attenuate long-term potentiation in hippocampal slices and substantially spared the N-methyl-D-aspartate component of excitatory postsynaptic currents, while dizocilpine maleate (6-10 microM) or D-2-amino-5-phosphovalerate (50 microM) completely blocked these phenomena. We suggest that the favorable kinetics of memantine interaction with N-methyl-D-aspartate channels may be partly responsible for its high index of therapeutic safety, and make memantine a candidate drug for use in many N-methyl-D-aspartate receptor-mediated human CNS disorders.
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PMID:Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. 969 19

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.
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PMID:Defective motor control of coughing in Parkinson's disease. 970 Jan 21

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetised rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100mg/kg i.p.) resulted in an increase in [11C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitisation was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170mg/kg/day). In the course of acute L-DOPA treatment (20mg/kg), extracellular GABA levels were reduced by approximately 20% in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease.
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PMID:Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET. 972 Sep 67

Thyrotropin-releasing hormone (TRH) has been reported to have some possibilities toward the treatment of affective CNS disorders. However, long term treatments with daily injections are often required. Effects of TRH-SR (sustained release microspheres of TRH) which is encapsulated in copoly (dl-lactic/glycolic acid) using an in-water drying method were investigated in experimental Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test and high performance liquid chromatography (HPLC) with an electrochemical detector (ECD). We have already reported that in adult Fischer rats killed 12 weeks after infection with JEV at the age of 13 days a marked decrease of tyrosine hydroxylase-positive neurons was found in the bilateral substantia nigra. TRH-SR (3 mg/kg per 2 weeks, 4 times injections, subcutaneous [s.c.]) improved bradykinesia observed in the JEV-induced parkinsonism rats. Dopamine (DA) concentrations in the JEV-infected rats were profoundly reduced in the striatum as compared with controls. TRH-SR (3 mg/kg, once, s.c.) increased DA in the striatum 7 days after the injection. Although the pathomechanism of post-encephalitic parkinsonism is different from that of Parkinson's disease and TRH possesses a variety of CNS effects as well, these results suggest that TRH-SR play a possible role in the treatment of Parkinson's disease in addition to post-encephalitic parkinsonism as a supportive drug of L-DOPA.
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PMID:Sustained release dosage of thyrotropin-releasing hormone improves experimental Japanese encephalitis virus-induced parkinsonism in rats. 974 96

A questionnaire-based case-control study was carried out on 86 patients with neurologist-confirmed idiopathic Parkinson's disease (PD) and 86 controls similar in sex and age. The control group was recruited in outpatient specialist centers of the same University Hospital (glaucoma, psoriasis vulgaris, essential arterial hypertension and renal diseases). Exposure was defined as occupational or residential contact with a given factor for at least 10 consecutive years prior to the onset of PD. Smoking habits were defined by exclusion of those subjects who never smoked. The following risk factors were identified: cranial trauma (OR: 2.88; 95% CI: 0.98-8.49), well water use (OR: 2.78; 95% CI: 1.46-5.28) and occupational exposure to industrial chemicals (OR: 2.13; 95% CI: 1.16-3.91). Among industrial chemicals, only organic solvents were identified as significant risk factors for PD (O.R. : 2.78, 95% C.I. : 1.23-6.26). Whereas no exposure to neurotoxic metals occurred among controls, making the assessment of the O.R. impossible, exposure pesticides and herbicides was similar in the two groups (O.R. : 1.15; 95% C. : 0.56-2-36). Smoking habits was negatively associated with PD (OR: 0.41; 95% CI: 0.22-0.75), confirming the "protective" role of tobacco smoking suggested by many studies. As a whole, these results support the role of environmental factors in the etiology of PD.
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PMID:A case-control study of occupational and environmental risk factors for Parkinson's disease in the Emilia-Romagna region of Italy. 974 32

Determining the relative contributions of environment and heredity to the cause of Parkinson's disease (PD) is more than an academic issue because its resolution dictates future research directions to an enormous degree. This article reviews new advances on both sides of this equation. The recent identification of the genetic mutation responsible for parkinsonism in a large Italian kindred is likely to provide exciting new research opportunities but the mutation does not appear to be responsible for the vast majority of PD. A large twin study also points away from genetic influences as important, at least in patients with disease beginning after the age of 50 years. On the other hand, genetic influences loom large in younger-onset disease. With regard to the environment, epidemiologic studies have provided only broad, thought-tantalizing clues to the cause of the disease. Although rural living, well-water consumption, and exposure to pesticides have emerged as potential risk factors, identification of specific agents is lacking, and aging remains as the only unequivocal risk factor for the disease. The surprisingly strong inverse relationship between cigarette smoking and PD provides an intriguing lead, but novel experimental avenues to pursue this observation are not readily obvious. The amyotrophic lateral sclerosis/dementia/parkinsonism complex in the western Pacific suggests the possibility of long-latency toxins, but pinning down a specific causative agent for this syndrome has eluded investigators to date. Despite the many obstacles ahead, however, research on PD appears to be more robust than ever, and our quest to find its cause appears to be under a full head of steam as we approach the 21st century.
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PMID:Epidemiology versus genetics in Parkinson's disease: progress in resolving an age-old debate. 974 72


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