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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.

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.

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).

The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Over the past 10years, several studies have focused on sexuality in patients with Crohn's disease. Very few of them specifically focused on perianal disease (PD). This study aimed to compare the prevalence of sexual dysfunction (SD) in Crohn's disease patients with active PD versus controls without active PD.

Patients from 14 French centres with active PD, defined by the presence of symptomatic ulceration, fistula or stenosis, were arbitrarily included. They were compared with controls from the existing SEXIA cohort. find more Men completed the International Index of Erectile Function (IIEF) and women the Female Sexual Function Index (FSFI). The primary end-point was SD defined by FSFI<26.55 in women and IIEF<42.9 in men.

Ninety-seven patients (64 women, 33 men) and 238 controls (131 women, 107 men) were included. SD was found in 66% of the female patients versus 50% of the controls (P=0.04). In the male population, SD was found in 30% of the cases versus 16% of the controls (P=0.06). Erectile dysfunction affected 46% of the male patients and 43% of the controls (P=0.8). On multivariate analysis, the predictive factor most strongly associated with SD in women was severely active anal PD defined by a perineal disease activity index >4 [OR=13.05 (2.32-73.44)].

Women with active PD had an increased prevalence of SD compared with controls without active PD. In the male population, the study was unable to determine whether there was a difference as it was underpowered.

Women with active PD had an increased prevalence of SD compared with controls without active PD. In the male population, the study was unable to determine whether there was a difference as it was underpowered.

Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3-deoxyglucosone and their derived advanced glycation end products (AGEs), and increased d-lactate, reflecting greater methylglyoxal flux.

We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone, free AGEs and d-lactate using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) in the treatment arm receiving 300mg irbesartan (n=121) and a placebo group (n=101) at baseline and after 1 and 2years. Effect of treaare not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No #NCT00317915).Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a. A combination of CPT-11 and nutlin-3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT-11 in the absence of nutlin-3a. Enhancement of the growth inhibitory activity of CPT-11 by nutlin-3a suggests a possible new combinatorial MM chemotherapy regimen.

Ovarian torsion is a common gynecological emergency of reproductive ages, occurring at rates of 2.7-7.4%. This study aimed to evaluate the antioxidant effects of Nebivolol (NEB) and histopathological changes in experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries.

Forty-eight adult female rats were randomly separated into six groups as group 1 (control) receiving an oral saline solution for 3 days; group 2 (I) that underwent ischemia for 3 h with the application of atraumatic vascular clips; group 3 (I/R); group 4 (I + NEB) receiving 10 mg/kg NEB by oral gavage 30 min prior to the ischemia induction; group 5 (I/R + NEB) receiving 10 mg/kg NEB, and group 6 (control + NEB) receiving oral 10 mg/kg NEB for 3 days before ischemia induction followed by consequent reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured biochemically.

The levels of MDA and tumor necrosis factor-alpha (TNF-α), and TUNEL assay positivity scores increased in the I and I/R groups.

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