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)

Using high-performance liquid chromatography with electrochemical detection, we determined serotonin in plasma from parkinsonian patients being treated with L-3,4-dihydroxyphenylalanine or N-(DL-seryl)-N'(2,3,4-trihydroxybenzyl)hydrochloride plus L-3,4-dihydroxyphenylalanine ("Sinemet") and in serum from a blood bank, from "normal" persons, and a pooled specimen from a hospital clinical laboratory. The values obtained for the two groups of Parkinson's disease patients showed no significant difference. Long-term storage on solid CO2 was xhown to be an adequate technique for preserving samples. The mean (+/-SEAM) normal value obtained for serotonin in serum was 146 +/- 46 microgram/liter (n = 23), a result in harmony with that previously obtained [Clin. Chem. 20, 812 (1974)] by fluorometry. In comparison to other methods for measurement of serotonin in serum or plasma, we believe that the present scheme offers greater selectivity, sensitivity, and precision.
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PMID:Liquid-chromatographic determination of serotonin in serum and plasma. 68 9

Occupational causes of parkinsonism have usually been identified by direct temporal association of an exposure with disease symptoms, although recently a latent period between exposure and disease causation is being investigated. This review presents the definition of parkinsonism as contrasted with Parkinson's disease, notes the general concepts important to the consideration of toxic effects on the central nervous system, and addresses each group of agents known to cause parkinsonism, including common sources of exposure, clinical course, and proposed mechanisms of toxicity. Agents discussed include manganese, carbon disulfide, organic solvents, carbon monoxide, and MTPT and similar agents.
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PMID:Occupational and environmental causes of parkinsonism. 149 32

Local cerebral blood flow (LCBF) and local tissue:blood partition, coefficient (L lambda) values were measured during CT scanning while patients with different types of Parkinson's syndrome (N = 14) inhaled a contrast mixture of 35-37 per cent stable xenon gas in oxygen. Single-compartment analysis fitted to infinity was used to calculate L lambda and LCBF values. Results were compared with results from normal age-matched volunteers (N = 24). Mean hemispheric (p less than 0.05) and subcortical (p less than 0.05) gray matter LCBF values were reduced in idiopathic Parkinson's disease (N = 11), compared to values from age-matched normals. Regionally, LCBF reductions included frontal (p less than 0.001), parietal cortex (p less than 0.05), caudate (p less than 0.05), lentiform nuclei (p less than 0.001) and thalamus (p less than 0.05) reductions. L lambda values were normal. Unilateral tremor and/or rigidity correlated directly with reduced LCBF in contralateral lentiform (p less than 0.01) and caudate (p less than 0.01) nuclei. In postencephalitic Parkinsonism (N = 1) LCBF reductions were diffuse, with normal L lambda values. In the akinetic form of Parkinsonism (N = 1) associated with lacunar infarcts, LCBF and L lambda reductions were patchy. In Parkinsonism following carbon monoxide poisoning (N = 1), LCBF values of gray and white matter were diffusely reduced and L lambda values were reduced in both pallidal regions. When dementia was present together with Parkinsonism (N = 3), LCBF reductions were more diffuse and severe. Dopaminergic deficiency correlated directly with reduced LCBF values, reflecting the severity of Parkinsonism.
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PMID:Xenon contrast CT-CBF measurements in parkinsonism and normal aging. 399 51

A case of major depressive disorder complicated by carbon monoxide (CO)-induced Parkinson's syndrome is reported. Computerized axial tomography (CAT) revealed bilateral globus pallidus necrosis. Clinical, CAT, and neuropathological findings in other cases of CO encephalopathy with and without parkinsonism are reviewed. The utility of CAT in the diagnostic workup and in following clinical course is discussed, as are the difficulties of making a diagnosis of an antecedent primary psychiatric disorder in the presence of neurological and psychiatric sequelae of CO intoxication. There was no clinical response to a tricyclic antidepressant, but both the mood and movement disorders responded fully to L-dopa. The implications of these findings with regard to the central neurochemical pathophysiology in this patient and in major depressive disorder in general are discussed.
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PMID:Major depression and carbon monoxide-induced parkinsonism: diagnosis, computerized axial tomography, and response to L-dopa. 402 Mar 69

Clinical and morphological studies of 73 cases of parkinsonism in patients aged 31 to 90 years were carried out. The following groups (types) of parkinsonism were differentiated: vascular, idiopathic, post-encephalitic, traumatic, toxic (after carbon monoxide poisoning), and of obscure etiology. cases of vascular parkinsonism constituting the largest group. Clinical and morphological features of parkinsonism of various etiology are described, including certain specific features of the disease in hypertensive and atherosclerotic patients. Forms underlain by a combination of the vascular and involutional-dystrophic processes are specified. An opinion is expressed that it would be erroneous to identify idiopathic parkinsonism (Parkinson's disease) as an involutional-dystrophic process with the post-encephalitic one.
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PMID:[Certain features of the clinical picture and pathomorphology of Parkinson disease of different etiology]. 741 21

Deficits in speech motor control and in the comprehension of syntax were observed as five members of the 1993 American Sagarmatha Expedition ascended Mt. Everest. We analyzed speech recordings and cognitive test scores of the climbers at different altitudes. The mean "voice onset time" interval that differentiates "voiced" stop consonants from their "unvoiced" counterparts (e.g., a [b] from a [p]) decreased from 24.0 ms at Base Camp to 5.4 ms at Camp Three. The time needed to comprehend simple spoken English sentences increased by 50% at higher altitudes, and was correlated with speech motor deterioration. This pattern of deficits is similar to that noted for Parkinson's disease and may reflect disruption of subcortical pathways to prefrontal cortex. Similar procedures could be used to remotely assess cognitive impairments caused by hypoxia, carbon monoxide or alcohol intoxication, or drugs, in order to monitor crew behavior in aeronautics and spaceflight operations, or to evaluate the treatment of neurodegenerative diseases such as Parkinson's disease.
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PMID:Speech production and cognitive deficits on Mt. Everest. 748 24

Brain imaging is performed using radiopharmaceuticals by single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET radiopharmaceuticals are classified according to blood-brain-barrier permeability, cerebral perfusion and metabolism receptor-binding, and antigen-antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99mTcO4-, [99mTc]DTPA, 201TI and [67Ga]citrate are excluded by normal brain cells, but enter into tumor cells because of altered BBB. These agents were used in the earlier period for the detection of brain tumors. SPECT perfusion agents such as [123I]IMP, [99mTc]HMPAO, [99mTc]ECD are lipophilic agents and therefore, diffuse into the normal brain. These tracers have been successfully used to detect various cerebrovascular diseases such as stroke, Parkinson disease, Huntington's disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and radiolabeled microspheres have been used for the measurement of cerebral blood flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include [123I]QNE, [123I]IBZM, and [123I]iomazenil. These tracers bind to specific receptors in the brain, thus displaying their distribution in various receptor-related cerebral diseases. Radioiodinated monoclonal antibodies were used for the detection of brain tumors. PET radiopharmaceuticals for brain imaging are commonly labeled with positron-emitters such as 11C, 13N, 15O, and 18F, although other radionuclides such as 82Rb, 62Cu and 68Ga also were used. The brain uptake of [13N]glutamate, [68Ga]EDTA and [82Rb]RbCl depends on the BBB permeability, but these are rarely used for brain imaging. Several cerebral perfusion agents have been introduced, of which [15O]water, [13N]ammonia, and [15O]butanol have been used more frequently. Regional CBF has been quantitated by using these tracers in normal and different cerebral disease states. Other perfusion agents include [15O]O2, [11C]CO, [11C]CO2, [18F]fluoromethane, [15O]O2, [11C]butanol, and [62Cu]PTSM. Among the PET cerebral metabolic agents, [18F]fluorodeoxyglucose (FDG) is most commonly used to detect metabolic abnormalities in the brain. Various brain tumors have been graded by [18F]FDG PET. This technique was used to detect epileptic foci by showing increased uptake in the foci during the ictal period and decreased uptake in the interictal period. Differentiation between recurrent tumors and radiation necrosis and the detection of Alzheimer's disease have been made successfully by [18F]FDG PET. Other PET metabolic agents such as [11C]deoxyglucose, and [11C]methylmethionine have drawn attention in the detection of brain tumors. [18F]fluorodopa is a cerebral neurotransmitter agent, which has been found very useful in the detection of Parkinson disease that shows reduced uptake of the tracer in the striatum of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Radiopharmaceuticals for brain imaging. 781 3

Mofegiline or MDL 72,974A ((E)-4-fluoro-beta-fluoromethylene benzene butanamine hydrochloride) is a selective enzyme-activated irreversible inhibitor of monoamine oxidase B, which is under development for use in the treatment of Parkinson's disease. Male beagle dogs were given single p.o. (20 mg/kg) and i.v. (5 mg/kg) doses of [14C]-Mofegiline. Total radioactivity excreted in urine and feces over 96 hr was, respectively, 75.5 +/- 3.8 and 6.3 +/- 3.4% of the dose after p.o. and 67.9 +/- 0.5 and 3.9 +/- 2.4% after i.v. administration. Unchanged drug in urine represented 3% of the dose after po and less than 1% after i.v. administration. Mofegiline was thus extensively metabolized in dogs, and urinary excretion was the major route of elimination of metabolites. HPLC, with on-line radioactivity detection, showed the presence of four major peaks (M1, M2, M3, and M4), representing respectively 50, 9, 5, and 0.5% of the administered dose excreted in 0-24 hr urine. TSP-LC-MS, FAB-MS, and NMR spectra of the purified metabolites were obtained. M1, the major metabolite in dogs, was shown to have undergone defluorination of the beta-fluoromethylene moiety, and one carbon addition. Its structure was confirmed to be a cyclic carbamate. M2 was a N-carbamoyl O-beta-D-glucuronide conjugate of parent drug. The formation of M1 and M2 is likely to involve initial reversible addition of CO2 to the primary amine function. M3 was a N-succinyl conjugate of the parent drug. M4 had also undergone defluorination to yield a urea adduct of an unsaturated alpha, beta aldehyde. Structures of M1 and M3 were further confirmed by comparing their MS and NMR spectra with those of authentic reference compounds. TSP-LC-MS ion chromatograms of human urine, obtained from two male volunteers after p.o. administration of 24 mg of drug, showed selected molecular ion peaks with the same retention time as the metabolites identified in dogs. In humans, these common metabolites represented a similar percentage of the administered dose to that in dogs. The present study demonstrates that NMR, TSP-LC-MS are complementary analytical techniques, which allow structural identification of unhydrolyzed drug conjugates. The formation of carbamates of amine-containing drugs may be more common than previously reported.
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PMID:Novel carbamate metabolites of mofegiline, a primary amine monoamine oxidase B inhibitor, in dogs and humans. 783 26

The main clinical features, pathophysiology and underlying mechanisms of drug-induced parkinsonism are reviewed. The clinical manifestations of drug-induced parkinsonism are often indistinguishable from idiopathic Parkinson's disease. However, some subtle differences may exist: for example drug-induced parkinsonism is often associated with tardive dyskinesias, bilateral symptoms and the absence of resting tremor, etc. Besides toxins (eg manganese, carbon monoxide or MPTP), many drugs are known to produce parkinsonism: dopamine blocking drugs (true neuroleptics used as antipsychotics: phenothiazines, butyrophenones, thioxanthenes but also sulpiride, "hidden" neuroleptics prescribed as anti-nausea or anti-vomiting drugs (such as metoclopramide and other benzamide derivatives), dopamine depleting drugs (reserpine, tetrabenazine), alpha-methyldopa, calcium channel blockers (flunarizine, cinnarizine, etc). The putative role of other drugs (eg fluoxetine, lithium, amiodarone) as well as the therapeutic management of this side effect are reviewed.
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PMID:Drug-induced parkinsonism: a review. 785 36

We studied the relative etiologic importance upon the development of Parkinson's disease (PD) of occupational exposure to herbicides and other compounds, ionizing radiation exposure, family history of PD and essential tremor, smoking, and history of various viral and other medical conditions. We identified patients (n = 130) with neurologist-confirmed idiopathic PD through contacts with Calgary general hospitals, long-term care facilities, neurologists, the Movement Disorder Clinic, and the Parkinson's Society of Southern Alberta, and selected two matched (by sex and age +/- 2.5 years) community controls for each case by random digit dialing. We obtained lifetime work, chemical, radiation, medical, and smoking exposure histories and family histories of PD and essential tremor by personal interviews, and analyzed the data using conditional logistic regression for matched sets. After controlling for potential confounding and interaction between the exposure variables, using multivariate statistical methods, having a family history of PD was the strongest predictor of PD risk, followed by head trauma and then occupational herbicide use. Cases and controls did not differ in their previous exposures to smoking or ionizing radiation; family history of essential tremor; work-related contact with aluminum, carbon monoxide, cyanide, manganese, mercury, or mineral oils; or history of arteriosclerosis, chicken pox, encephalitis, hypertension, hypotension, measles, mumps, rubella, or Spanish flu. These results support the hypothesis of a multifactorial etiology for PD, probably involving genetic, environmental, trauma, and possibly other factors.
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PMID:Parkinson's disease: a test of the multifactorial etiologic hypothesis. 817 May 64


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