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Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.
Miranda-Díaz, AG, García-Sánchez, A, Cardona-Muñoz, EG
Oxidative medicine and cellular longevity. 2020;:6281454
Abstract
Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.
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Adaptive Eating Device: Performance and Satisfaction of a Person with Parkinson's Disease.
Cavalcanti, A, Amaral, MF, Silva E Dutra, FCM, Santos, AVF, Licursi, LA, Silveira, ZC
Canadian journal of occupational therapy. Revue canadienne d'ergotherapie. 2020;(3):211-220
Abstract
BACKGROUND.: Individuals with Parkinson's disease (PD) can experience motor impairments related to their hand-use that restrict participation in daily activities. Feeding is one activity impacted by this health condition. The use of adapted utensils can improve performance and independence in this activity. PURPOSE.: To investigate if a locally designed and made eating-adaptive device helps a person with PD to improve their feeding performance. METHOD.: Single-case ABC-type experimental design. Performance and satisfaction of a 60-year-old man with PD were assessed during feeding tasks in 70 sequential days in three phases. Celeration Line, Two-Standard Deviation Band, and Visual Analysis were the methods used for data analysis. FINDINGS.: Performance and satisfaction increased significantly after the introduction of the adaptive eating device. The addition of weight also contributed to the increase in the participant's performance. IMPLICATIONS.: Adaptive eating device with low production costs and possibility of customized adjustments improves performance of people with PD.
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A Clinical Trial of Isradipine: What Went Wrong?
Maiti, B, Perlmutter, JS
Annals of internal medicine. 2020;(9):625-626
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An evaluation of subcutaneous apomorphine for the treatment of Parkinson's disease.
Müller, T
Expert opinion on pharmacotherapy. 2020;(14):1659-1665
Abstract
INTRODUCTION Heterogeneity of symptoms and individual variability of progression characterizes Parkinson's disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients' needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications. AREAS COVERED This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research. EXPERT OPINION Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.
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Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial.
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Annals of internal medicine. 2020;(9):591-598
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Abstract
BACKGROUND Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD). OBJECTIVE To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD. DESIGN Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842). SETTING 57 Parkinson Study Group sites in North America. PARTICIPANTS Patients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment. INTERVENTION 5 mg of immediate-release isradipine twice daily or placebo for 36 months. MEASUREMENTS The primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures. RESULTS 336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness. LIMITATION The isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects. CONCLUSION Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD. PRIMARY FUNDING SOURCE National Institute of Neurological Disorders and Stroke.
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Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.
Daneshvar Kakhaki, R, Ostadmohammadi, V, Kouchaki, E, Aghadavod, E, Bahmani, F, Tamtaji, OR, J Reiter, R, Mansournia, MA, Asemi, Z
Clinical neurology and neurosurgery. 2020;:105878
Abstract
OBJECTIVE This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (β -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (β -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (β -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (β -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (β -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (β 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (β 77.08 μmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (β -1.79 μIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (β -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (β -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (β -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.
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Isradipine Versus Placebo in Early Parkinson Disease.
Annals of internal medicine. 2020;(9)
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Association between vitamin D receptor polymorphisms and susceptibility to Parkinson's disease: An updated meta-analysis.
Gao, J, Teng, J, Liu, Z, Cai, M, Xie, A
Neuroscience letters. 2020;:134778
Abstract
The relationships between vitamin D receptor (VDR) gene polymorphisms, particularly ApaI, BsmI, FokI, and TaqI, and Parkinson's disease (PD) has received increasing attention in the research community. However, as the results yielded by this increased research have hitherto conflicted, we performed an updated meta-analysis of reports on the relationships between VDR polymorphisms and PD published before October 2019 that we collected from the PUBMED, EMBASE, EBSCO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The ten articles that met our screening criteria included 2782 patients and 3194 healthy controls. All the data that we received were analyzed with Stata 12.0 statistical software. The odds ratio (OR) and 95 % confidence intervals (CIs) were used to determine the relationship between VDR gene diversity and PD. While we did not find a significant correlation between the ApaI, BsmI, and TaqI polymorphisms and the risk of PD in any of the considered genetic models, we found a clear association between the FokI polymorphism and susceptibility to PD (C vs. T: OR = 1.246, 95 % CI: 1.101-1.411, P = 0; CC vs. TT: OR = 1.630, 95 % CI: 1.243-2.139, P = 0; CT vs. TT: OR = 1.382, 95 % CI: 1.059-1.804, P = 0.017; CC + CT vs. TT: OR = 1.491, 95 % CI: 1.159-1.919,P = 0.002; CC vs. CT + TT: OR = 1.261, 95 % CI: 1.062-1.496, P = 0.008). Our subgroup analysis performed according to ethnicity revealed that FokI increased the risk of PD in Asian populations (C vs. T: OR = 1.261, 95 % CI: 1.080-1.472, P = 0.003; CC vs. TT: OR = 1.664, 95 % CI: 1.189-2.330, P = 0.003; CT vs.TT: OR = 1.387, 95 % CI: 1.000-1.925, P = 0.05; CC + CT vs. TT: OR = 1.497, 95 % CI: 1.098-2.042, P = 0.011; CC vs. CT + TT: OR = 1.285, 95 % CI: 1.036-1.593, P = 0.022). Overall, the gene polymorphism of FokI only increases the risk of PD among Asian populations. Given the limited sample size of this study, the findings should be carefully explained.
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Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study.
Hattori, N, Tsuboi, Y, Yamamoto, A, Sasagawa, Y, Nomoto, M, ,
Parkinsonism & related disorders. 2020;:17-23
Abstract
INTRODUCTION Safinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off. METHODS This 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index. RESULTS A total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p < 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%). CONCLUSION As an adjunct to l-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.
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Safinamide in the treatment of Parkinson's disease.
Müller, T
Neurodegenerative disease management. 2020;(4):195-204
Abstract
The deficiency pattern of neurotransmitters is heterogeneous in patients with Parkinson's disease. Consequence is an individual variable expression of motor and nonmotor features. They respond to agents with a broader spectrum of mode of actions, whereas dopamine substitution only targets impaired motor behavior. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition and modulation of voltage-dependent sodium- and calcium channels with consecutive decline of glutamate release. Safinamide improves motor and nonmotor symptoms. Combination of safinamide with the catechol-O-methyltransferase inhibitor opicapone in one capsule is a promising future treatment alternative, which simplifies drug therapy in Parkinson's disease. Both agents complement each other in terms of application mode and efficacy on motor complications as adjuncts to levodopa therapy.