Objective To determine if the antioxidant N-acetylcysteine is able to alter peripheral and central redox capabilities in patients with Parkinson’s or Gaucher disease. Methods The study included non-demented adult subjects: 3 with Parkinson’s disease, 3 with Gaucher disease and 3 healthy controls. Baseline brain glutathione concentrations were measured using 7 Tesla magnetic resonance spectroscopy. Baseline blood reduced-to-oxidized glutathione ratios were determined for each subject. Brain glutathione concentrations and blood redox ratios were then determined during and at specified time points after a single, 150mg/kg N-acetylcysteine infusion. Results N-acetylcysteine increased blood glutathione redox ratios in those with Parkinson’s and Gaucher disease and healthy controls, which was followed by an increase in brain glutathione concentrations in all subjects. Conclusions This is the first demonstration that with magnetic resonance spectroscopy, it is possible to directly measure and monitor increases in brain glutathione levels in the human brain in response to a single, intravenous administration of N-acetylcysteine. This work shows the potential utility of magnetic resonance spectroscopy monitoring which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for Parkinson’s disease, Gaucher disease and other neurodegenerative disorders.

ObjectiveTo examine the feasibility, acceptability, and preliminary effects of Hatha yoga on oxidative stress, motor function, and non-motor symptoms among individuals with Parkinson’s disease (PD).MethodsThe study has a pilot randomized controlled trial design with two arms: an immediate treatment group and a wait-list control group. The yoga-for-PD program was implemented via twice weekly 60-min group-based classes for 12 weeks. Participants were assessed at baseline, 12 weeks, and 6 months post-intervention. Outcome measures included oxidative stress, motor function, physical activity, cognitive function, sleep quality, and quality of life. Data on program acceptability and yoga adherence were collected during the intervention and at 6 months post-intervention.ResultsParticipants (n = 20) had a mean age of 63 years (SD 8, range 49–75) and disease duration 4.8 years (SD 2.9, range 1–13). All participants had mild-moderate disease severity; 18 (90%) were on dopaminergic medications. Seventeen participants (85%) attended at least 75% of the classes and 4 (20%) attended all classes. Most participants (n = 17) reported they “definitely enjoyed” the intervention program. No adverse events were reported. At 12 weeks, there were no major differences in blood oxidative stress markers between the two groups. Motor function based on the Unified Parkinson’s Disease Rating Scale was better in the treatment group, but their scores on sleep and outlook in Parkinson’s Disease Quality of Life (PDQUALIF) Scale and the physical activity levels based on the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire were worse than those of the control group. In within-group comparisons, motor function, cognitive function, and catalase improved but three PDQUALIF domains (social and role function, sleep, and outlook) and physical activity level worsened by the end of the yoga intervention program compared to baseline. The response rate for the 6-month follow-up survey was 74% (n = 14) with six participants (43%) who signed up for a yoga class and four (29%) who practiced it independently. Health problems were the main barrier to yoga practice.ConclusionYoga is feasible and acceptable and may serve as a complementary method for improving motor function in PD. Further research using a larger sample size is needed to determine its impact on oxidative stress and non-motor symptoms.Trial registrationClinicalTrials.gov Registration Number: NCT02509610031.

Parkinson's disease (PD) is associated with oxidative stress and decreased nigral glutathione (GSH), suggesting that therapies that boost GSH may have a disease-modifying effect. Intravenous administration of a high dose of N-acetylcysteine (NAC), a well-known antioxidant and GSH precursor, increases blood and brain GSH in individuals with PD and with Gaucher disease and in healthy controls. To characterize the pharmacokinetics of repeated high oral doses of NAC and their effect on brain and blood oxidative stress measures, we conducted a 4-week open-label prospective study of oral NAC in individuals with PD (n = 5) and in healthy controls (n = 3). Brain GSH was measured in the occipital cortex using H-MRS at 3 and 7 tesla before and after 28 days of 6000 mg NAC/day. Blood was collected prior to dosing and at predetermined collection times before and after the last dose to assess NAC, cysteine, GSH, catalase, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations and the reduced-to-oxidized GSH ratio (GSH/ glutathione disulfide [GSSG]). Symptomatic adverse events were reported by 3 of the 5 subjects with PD. NAC plasma concentration-time profiles were described by a first-order absorption, 1-compartment pharmacokinetic model. Although peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline, indicators of oxidative damage, that is, measures of lipid peroxidation (4-HNE and MDA) were unchanged. There were no significant increases in brain GSH, which may be related to low oral NAC bioavailability and small fractional GSH/GSSG blood responses. Additional studies are needed to further characterize side effects and explore the differential effects of NAC on measures of antioxidant defense and oxidative damage.

Carbamazepine is a widely prescribed antiepileptic drug. Due to a lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100 mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with LC-MS and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (L/hr/kg) was significantly lower in men (0.039±0.017) than women (0.049±0.018;p=0.007) and in African Americans (0.039±0.017) when compared to Caucasians (0.048±0.018;p=0.019). Half-life was significantly longer in men than women as well as in African Americans when compared to Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.

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