Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levodopa treatment in patients with Parkinson's disease (PD) is known to cause elevation in serum homocysteine levels. We investigated whether this increase in homocysteine level influences cerebral vascular flow velocity and resistance using transcranial Doppler (TCD). This study included 17 patients with de novo PD. Homocysteine levels and TCD parameters at middle cerebral artery were investigated before and after 3 months of levodopa treatment. Correlation analyses were done between changes in homocysteine levels and TCD parameters. After 3 months of levodopa treatment, homocysteine level increased significantly from 13.3mg/dL to 17.0 mg/dL (p < 0.001), but there were no meaningful changes in mean velocity (MV) and pulsatility index (PI). Correlation analysis revealed that the changes in homocysteine level had negative correlation with MV (r = -0.53, p = 0.027) and positive correlation with PI (r = 0.55, p = 0.028). Our study infer that although short-term treatment of levodopa itself does not cause overall alteration of cerebral blood flow velocities and resistances, patients who has greater degree of increased homocysteine level may still be at a risk of developing cerebral vascular stiffness.
 ...
PMID:The effect of levodopa treatment on cerebral hemodynamics in patients with Parkinson's disease: serial transcranial Doppler studies. 1981 47

Levodopa (LD) is the oldest, most efficacious and best-tolerated drug for dopaminergic substitution of patients with Parkinson's disease (PD). Its main drawback is its short half-life, which supports onset of motor complications in the long term. Therefore well-informed PD patients mostly accept LD therapy as late as possible. Recent LD trials indicate that a combination of LD with carbidopa (CD) and the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) may reduce the onset of these motor complications to a certain extent. This observation is further supported by pharmacokinetic trials and experimental research, but there is still a need to confirm this in a clinical trial, which is under way. Additionally, combined LD/CD/EN was superior to LD/CD administration regarding cognition, muscle behavior and gastrointestinal function in small clinical trials. Moreover there is accumulating evidence that combined COMT inhibition with LD administration reduces homocysteine synthesis. In the long term, homocysteine elevation supports onset of arteriosclerosis-related disorders, which are more frequent in PD patients according to epidemiological studies than in the normal healthy population. The introduction of LD/CD/EN in one tablet supported patients' preference of COMT inhibition as an essential component of LD/DDI therapy, as this combination reduced number and size of tablets.
 ...
PMID:Levodopa/carbidopa and entacapone in the treatment of Parkinson's disease: efficacy, safety and patient preference. 1993 45

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 microg vitamin B(12) daily), alpha-lipoic acid (alpha-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005-0.023). BMD changes in the alpha-LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the alpha-LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% +/- 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 +/- 0.024 ng/mL) than control group (0.628 +/- 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa.
 ...
PMID:Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease. 1993 51

Increasing evidence has been suggested that hyperhomocysteinemia is a risk factor of neurodegenerative diseases, although, the underlying mechanisms have not been elucidated. Here, we found peripheral application of homocysteine increases X-box-binding protein 1 (XBP1) splicing in the several areas of the mice brain, such as hippocampus, hypothalamus and cortex. Time-course experiments indicated that XBP1 splicing was observed from 2h, which was decreased thereafter. On the other hand, we did not observe GRP78 or CHOP induction in homocysteine-treated mice brain. As XBP1 is spliced in response to endoplasmic reticulum (ER) stress and ER stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease and Parkinson's disease, homocysteine-induced XBP1 splicing would be a key mechanism for such diseases.
 ...
PMID:Homocysteine induces X-box-binding protein 1 splicing in the mice brain. 2001 21

The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal-and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.
 ...
PMID:Possible treatment concepts for the levodopa-related hyperhomocysteinemia. 2002 36

This study addresses the effects of 52 weeks of treatment with the NMDA glutamate receptor antagonist memantine on motor, cognitive, and mental disorders in patients with Parkinson's disease complicated by dementia, as compared with a control group of patients not treated with memantine. Patients of the experimental group (32 subjects) received memantine (20 mg/day), while patients in the control group continued on antiparkinsonism treatment alone. Cognitive, psychiatric, and motor symptoms were assessed before the study and then at the ends of weeks 12, 24, and 52, using clinical assessment, rating scales, and neuropsychological tests. Plasma homocysteine levels were measured by HPLC. Patients treated with memantine had better measures on the MMSE (p < 0.05), ADAS-cog (p < 0.05), clock drawing test (p < 0.05), and FAB (p < 0.01) as compared with the control group by the end of study week 24. Members of the group of patients with high homocysteine levels mounted significantly better responses with memantine treatment, as compared with patients of the control group with high homocysteine levels but not receiving memantine, at the ends of study weeks 24 and 52, in terms of all rating scales (UPDRS, MMSE, ADAS-cog, D-KEFS Verbal Fluency Test, FAB. NPI, and DAD, p < 0.05). By the end of week 52, significant changes in points scores on the NPI-12 scale from baseline were in favor of patients receiving memantine, this applying to the disinhibition (p = 0.006), irritability (p = 0.04), anxiety (p = 0.04), and hallucinations (p = 0.048) subscales. The presence of hyperhomocysteinemia may indicate faster progression of both motor and cognitive impairments in Parkinson's disease. Prolonged memantine treatment of patients with Parkinson's disease complicated by dementia leads to improvements in cognitive functions, stabilization of motor impairments, and decreases in the severity of mental disorders, especially in patients with hyperhomocysteinemia.
 ...
PMID:Use of memantine (akatinol) for the correction of cognitive impairments in Parkinson's disease complicated by dementia. 2003 5

This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma.
 ...
PMID:Homocysteine, vitamin determinants and neurological diseases. 2003 53

Parkinson's disease (PD) patients have been reported to have lower bone mineral density (BMD) and higher fracture risk than individuals without PD. We assessed the association between hyperhomocysteinemia due to levodopa intake and BMD in PD patients. We measured serum homocysteine (Hcy) concentrations and BMD in the proximal femur and lumbar spine of PD patients aged 55 years or older (n = 95) and three age-/gender-matched control subjects (n = 285). The prevalence of osteoporosis was higher in both men (2.5-fold) and women (1.7-fold) with PD than in controls, and adjusted odds ratios for osteoporosis were 3.57 (95% confidence interval [CI], 1.25-10.20) for men and 2.54 for women (95% CI, 1.31-4.93) with PD. Serum Hcy concentrations were significantly higher in PD patients (median = 13.0 micromol/l) than controls (median = 11.5 micromol/l) (P = 0.005). Serum Hcy concentrations were independently associated with BMD values at all proximal femur sites in all subjects (P = 0.005 to 0.012). In PD patients, higher serum Hcy concentrations were independently associated with higher fracture risk (P = 0.029). PD patients taking higher doses of levodopa had significantly higher serum Hcy concentrations (P = 0.013), and greater levodopa intake was associated with lower BMD values in some areas (P = 0.008 to 0.029). In conclusion, these findings indicate that hyperhomocysteinemia due to levodopa intake may be one additional risk factor for osteoporosis and fracture in PD patients. Reducing Hcy may be a therapeutic modality for treating osteoporosis in PD patients taking levodopa.
 ...
PMID:Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson's disease. 2004 22

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case-control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0.87, 0.70 and 0.11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0.56 (0.33, 0.94), 0.69 (0.38, 1.25) and 0.48 (0.23, 0.99), respectively (P for trend = 0.10). In conclusion, in the present case-control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.
 ...
PMID:Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case-control study in Japan. 2033 75

To investigate the effect of L-3,4-dihydroxyphenylalanine (L-dopa) therapy on homocysteine (HC) concentration in patients with Parkinson's disease (PD), the concentrations in cerebrospinal fluid (CSF) of total HC and methionine (Met) were compared between 18 patients with PD before and after treatment with L-dopa and 16 neurologically normal control patients. Concentrations of total HC in patients with PD were significantly higher following L-dopa therapy (169+/-27 nM) than before treatment (111+/-22 nM) and than in controls (85+/-25 nM) (patients with PD before L-dopa treatment vs. controls, p<0.005; patients with PD after L-dopa treatment vs. before treatment, p<0.0001). Conversely, concentrations of total Met in patients with PD were significantly lower after L-dopa therapy (5.3+/-1.7 microM) than before L-dopa therapy (6.8+/-1.9 microM) (p<0.001). These findings in patients with PD suggest that L-dopa therapy enhances intracerebral methylation and elevates concentration of HC.
 ...
PMID:L-Dopa therapy increases homocysteine concentration in cerebrospinal fluid from patients with Parkinson's disease. 2035 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>