Hence, the polyuria/polydipsia effect produced by ME lesions appears to be consistent during the first 24 h but might later be related to the availability of standard food and is completely abolished under EPZ5676 food deprivation conditions. Preference for the hypertonic solution supports the volemic component of this syndrome and demonstrates the need for appropriate amounts of hypertonic nutrients to be consumed during the first 24 h. (c) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Background Oral fumarate (BG00012) might have dual anti-inflammatory and neuroprotective effects. Our aim was to assess the efficacy and safety of BG00012 in patients with

relapsing-remitting multiple sclerosis.

Methods 257 patients, aged 18-55 years, with relapsing-remitting multiple sclerosis were randomly JSH-23 in vitro assigned to receive 120 mg once daily (n=64), 120 mg three times daily (n=64), or 240 mg three times daily (n=64) BG00012, or placebo (n=65) for 24

weeks. During an extension period of 24 weeks for safety assessment, patients treated with placebo received BG00012 240 mg three times daily. The primary endpoint was total number of new gadolinium enhancing (GdE) lesions on brain MRI scans at weeks 12, 16, 20, and 24. Additional endpoints included cumulative number of new GAE lesions (weeks 4-24), new or enlarging T2-hyperintense lesions, new T1-hypointense lesions at week 24, and annualised relapse rate. Analysis was done on the efficacy-evaluable population. Safety and tolerability were also assessed. This study is registered with ClinicalTrials.gov, number NCT00168701.

Findings Treatment with BG00012 240 mg three times daily reduced by 69% the mean total number of new GdE lesions from week 12 to 24 compared

with placebo (1 . 4 vs 4.5, p<0 . 0001). It also reduced number of new or enlarging T2-hyperintense (p=0 . 0006) and new T1-hypointense why (p=0.014) lesions compared with placebo. BG00012 reduced annualised relapse rate by 32% (0.44 vs 0 . 65 for placebo; p=0 . 272). Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain, flushing, and hot flush. Dose-related adverse events in patients on BG00012 were headache, fatigue, and feeling hot.

Interpretation The anti-inflammatory effects and favourable safety profile of BG00012 warrant further long-term phase III studies in large patient groups.

Funding Biogen Idec, Inc.”
“Olfactory dysfunction is common in patients with Parkinson disease (PD) and has been attributed to early pathological deposition of Lewy bodies and Lewy neurites in primary olfactory centers. However, olfactory deficits do not always worsen over time despite progression of disease raising the possibility of additional pathobiological mechanisms contributing to olfactory functions in PD, such as changes in olfactory neurotransmitter functions.