Open-Label Study of Sleep Disturbances in Patients with Parkinson's Disease Treated with Rasagiline.

BACKGROUND: The prevalence of sleep disturbances among patients with Parkinson's disease (PD) is estimated to occur in 37% to 98% of patients. Sleep disturbances have been associated with a reduced quality of life for patients with PD. The objective of this study was to assess the impact of rasagiline treatment on the severity of sleep disturbances among patients with idiopathic PD. METHODS: In this open-label, multicentre study, 110 adult patients with idiopathic PD were treated with rasagiline either as monotherapy or as adjunct therapy. The primary endpoint was the change in severity of sleep disturbances, assessed with the PD Sleep Scale from baseline to month 2. Exploratory endpoints included change in daytime sleepiness, assessed with the Epworth Sleep Scale, treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication, patient's overall improvement or deterioration over time measured with the Clinical Global Impression of Improvement, tolerability, and safety. FINDINGS: Patients treated with rasagiline as mono- or adjunct therapy showed a statistically significant improvement in sleep quality after 2 months. There was no change in daytime sleepiness. Overall, patients were satisfied with rasagiline treatment with a mean Treatment Satisfaction Questionnaire for Medication [standard deviation] total score at month 2 of 68% [16.1]. At the end of study, 64 patients (65.9%) were judged, by the investigator, as being at least minimally improved from baseline on the Clinical Global Impression of Improvement. Rasagiline was safe and well-tolerated. INTERPRETATION: Rasagiline as mono- or adjunct-therapy may improve sleep experience in patients with PD in the short term.

Upregulation of expression of the chemokine receptor CCR5 by hydrogen peroxide in human monocytes.

The objective of this study was to test the hypothesis that an oxidative stress can serve as a signal to regulate the expression of CCR5. When human monocytes were exposed to graded concentration of hydrogen peroxide (H(2)O(2)), CCR5 mRNA levels increased maximally at 4 h of exposure to 200 microM of H(2)O(2) and decreased by 24 h of treatment. Pretreatment of monocytes with the NF-kappaB inhibitor BAY 11-8072 blocked the H(2)O(2)-induced augmentation of CCR5 mRNA expression, suggesting a role for this transcription factor in the regulation of CCR5 expression. CCR5 protein expression on the plasma membrane was also increased by treatment with H(2)O(2,) as assessed by flow cytometry. This was accompanied by enhanced responsiveness of H(2)O(2)-pretreated monocytes to the CCR5 ligand MIP-1beta in terms of chemotaxis and c-fos gene activation. Our results suggest that oxidative stress may indeed modulate the expression of chemokine receptors and thus contribute to regulation of the inflammatory process.