Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study.

BACKGROUND AND PURPOSE: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. METHODS: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. RESULTS: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary end-point: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 ± 2.9 to 8.9 ± 1.8; P = 0.27). CONCLUSION: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Can Bangladesh produce enough cereals to meet future demand?

Bangladesh faces huge challenges in achieving food security due to its high population, diet changes, and limited room for expanding cropland and cropping intensity. The objective of this study is to assess the degree to which Bangladesh can be self-sufficient in terms of domestic maize, rice and wheat production by the years 2030 and 2050 by closing the existing gap (Yg) between yield potential (Yp) and actual farm yield (Ya), accounting for possible changes in cropland area. Yield potential and yield gaps were calculated for the three crops using well-validated crop models and site-specific weather, management and soil data, and upscaled to the whole country. We assessed potential grain production in the years 2030 and 2050 for six land use change scenarios (general decrease in arable land; declining ground water tables in the north; cropping of fallow areas in the south; effect of sea level rise; increased cropping intensity; and larger share of cash crops) and three levels of Yg closure (1: no yield increase; 2: Yg closure at a level equivalent to 50% (50% Yg closure); 3: Yg closure to a level of 85% of Yp (irrigated crops) and 80% of water-limited yield potential or Yw (rainfed crops) (full Yg closure)). In addition, changes in demand with low and high population growth rates, and substitution of rice by maize in future diets were also examined. Total aggregated demand of the three cereals (in milled rice equivalents) in 2030 and 2050, based on the UN median population variant, is projected to be 21 and 24% higher than in 2010. Current Yg represent 50% (irrigated rice), 48-63% (rainfed rice), 49% (irrigated wheat), 40% (rainfed wheat), 46% (irrigated maize), and 44% (rainfed maize) of their Yp or Yw. With 50% Yg closure and for various land use changes, self-sufficiency ratio will be > 1 for rice in 2030 and about one in 2050 but well below one for maize and wheat in both 2030 and 2050. With full Yg closure, self-sufficiency ratios will be well above one for rice and all three cereals jointly but below one for maize and wheat for all scenarios, except for the scenario with drastic decrease in boro rice area to allow for area expansion for cash crops. Full Yg closure of all cereals is needed to compensate for area decreases and demand increases, and then even some maize and large amounts of wheat imports will be required to satisfy demand in future. The results of this analysis have important implications for Bangladesh and other countries with high population growth rate, shrinking arable land due to rapid urbanization, and highly vulnerable to climate change.

Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.

In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides.

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.