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)

Neurogenic dysphagia results from sensorimotor impairment of the oral and pharyngeal phases of swallowing due to a neurologic disorder. The symptoms of neurogenic dysphagia include drooling, difficulty initiating swallowing, nasal regurgitation, difficulty managing secretions, choke/cough episodes while feeding, and food sticking in the throat. If unrecognized and untreated, neurogenic dysphagia can lead to dehydration, malnutrition, and respiratory complications. The symptoms of neurogenic dysphagia may be relatively inapparent on account of both compensation for swallowing impairment and diminution of the laryngeal cough reflex due to a variety of factors. Patients with symptoms of oropharyngeal dysphagia should undergo videofluoroscopy of swallowing, which in the case of neurogenic dysphagia typically reveals impairment of oropharyngeal motor performance and/or laryngeal protection. The many causes of neurogenic dysphagia include stroke, head trauma, Parkinson's disease, motor neuron disease and myopathy. Evaluation of the cause of unexplained neurogenic dysphagia should include consultation by a neurologist, magnetic resonance imaging of the brain, blood tests (routine studies plus muscle enzymes, thyroid screening, vitamin B12 and anti-acetylcholine receptor antibodies), electromyography/nerve conduction studies, and, in certain cases, muscle biopsy or cerebrospinal fluid examination. Treatment of neurogenic dysphagia involves treatment of the underlying neurologic disorder (if possible), swallowing therapy (if oral feeding is reasonably safe to attempt) and gastrostomy (if oral feeding is unsafe or inadequate).
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PMID:Dysphagia associated with neurological disorders. 820 77

Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.
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PMID:Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism. 1099 May 20

The authors evaluated the prevalence of dementia in centenarians. In this population-based survey, persons living in Denmark who turned 100 during the period April 1, 1995--May 31, 1996 (N = 276) were interviewed and examined at their residences. Additional health information was retrieved from medical files, including the National Discharge Registry. A participation rate was 75%, and no differences were found between participants and nonparticipants regarding sex and type of housing. The prevalence of mild to severe dementia in centenarians was 51%; 37% had no signs of dementia. Among the 105 demented centenarians, 13 (12%) had diseases (vitamin B12 and folic acid deficiencies, hypothyroidism, Parkinson's disease) that could contribute to a dementia diagnosis. Of the remaining 92 demented participants, 46 (50%) had 1 one or more cerebro- or cardiovascular diseases known to be risk factors in the development of dementia. The prevalence of these risk factors was the same in demented and nondemented participants, whereas hypertension was significantly more frequent in nondemented than demented participants. Dementia is common but not inevitable in centenarians. Cerebro- and cardiovascular diseases are equally common in demented and nondemented persons.
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PMID:Dementia is not inevitable: a population-based study of Danish centenarians. 1131 33

Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson's disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age +/- SD = 66.2+/-8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4+/-34.9 to 179.2+/-23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.
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PMID:High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients. 1533 94

There is a well-known interaction between vitamin B12, folate, and homocysteine. More unknown is the fact that this interaction might be affected by long-term treatment with levo-dopa in patients with Parkinson's disease. An increase in homocysteine levels and tissue deficiency of vitamin B12 and folate may occur. The responsible doctor should be liberal in checking vitamin B12 and folate status and supplement with appropriate vitamins when needed.
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PMID:[Treatment with levodopa can affect latent vitamin B 12 and folic acid deficiency. Patients with Parkinson disease runt the risk of elevated homocysteine levels]. 1453 Nov 26

In this article, a particular emphasis has been placed on the conceptual development and understanding of the unique pathogenic changes that are indigenous to the striatal dopaminergic neurons as an important etiological factor in human Parkinson's disease (PD) as well as on the understanding of their clinical implications. Specifically, I have discussed the etiological roles of central nervous system dopamine oxidation in PD, along with a critical review of the available evidence in support of the proposed hypotheses. The chemically-reactive dopamine quinone/semiquinone intermediates are known to be highly neurotoxic and potentially genotoxic. There is considerable evidence for the suggestion that the long-term use of levodopa accelerates the progression of PD. In comparison, centrally-acting non-catechol dopamine receptor agonists would be an excellent alternative to levodopa for the treatment of PD (particularly for late-stage PD) because these agents would not undergo redox cycling to cause oxidative neuronal damage. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of catecholamine neurotransmitters is a crucial first-line detoxification pathway, and its role in the causation and prevention of PD is also discussed. On the basis of the modulation of COMT-mediated methylation of catecholamines, it is mechanistically explained that hyperhomocysteinemia would be a pathogenic factor in PD whereas vitamins B6, B12, and folate would be a protective factor. Lastly, according to the mechanistic understanding developed here, a novel dietary strategy is proposed that is specifically tailored toward lowering the risk of human PD, which includes eating a nutritionally-balanced diet that contains adequate (but not excessive) amounts of fruits and vegetables, along with adequate dietary supplementation of S-adenosyl-L-methionine, vitamins C, B6, B12, and folate. It is believed that these conceptual developments would also aid in our better understanding of other age-related neurodegenerative disorders, such as Alzheimer's and Huntington's diseases.
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PMID:CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson's disease. 1476 63

Homocysteine is a thyol amino acid resulting from a methylation of methionine, an essential amino acid derived from dietary proteins. Homocysteine is metabolized through two pathways: remethylation and transsulfuration, which use as confactors folic acid, vitamin B6 and vitamin B12. The genetic and acquired factors that induce a reduction of levels of folic acid, vitamin B6 and vitamin B12 cause an increase of plasma levels of homocysteine. Numerous clinical studies showed a relationship between hyperhomocysteinemia, cerebrovascular diseases and Alzheimer disease. The hyperhomocysteinemia is also demonstrated in patients with Parkinson disease treated with levodopa and in the epileptic patients treated with anticonvulsant drugs. Nevertheless, so far it is not fully clear how significant is the relationship between the hyperhomocysteinemia and the above-mentioned neurological diseases.
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PMID:[Hyperhomocysteinemia in neurologic diseases]. 1530 48

Certain mutations (TT homozygous; CT heterozygous; CC wild-type) of the methylenetetrahydrofolate (MTHFR) gene and long-term levodopa application in patients with Parkinson's disease (PD) support onset of hyperhomocysteinemia. Total plasma homocysteine (t-hcys) depends on B6, B12, folic acid, all of which support remyelination from t-hcys to methionine. Objective of this trial were to compare B6, B12, folic acid and t-hcys levels in plasma of 83 levodopa treated PD patients and 44 controls. PD patients with the CT or TT genotype had significant higher t-hcys levels than controls or PD patients with the CC allele. Concentrations of B6 or B12 did not differ, but folic acid was significant higher in PD patients with the CT mutation. We recommend MTHFR genotyping, t-hcys monitoring and early vitamin supplementation in PD patients. The folic acid increase in PD patients with the CT allele is hypothetically due to an endogenous upregulation of folic acid absorption to decrease t-hcys.
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PMID:MTHFR C677T polymorphism, folic acid and hyperhomocysteinemia in levodopa treated patients with Parkinson's disease. 1535 85

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT-I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT-I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT-I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa-treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT-I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT-I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT-I effectively reduces HHcy.
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PMID:Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients. 1539 46

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.
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PMID:Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients. 1587 87


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