Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT)–PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas

A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients

The Charcot-Marie-Tooth Neuropathy Score (CMTNS) was developed as a main efficacy endpoint for application in clinical trials of Charcot-Marie-Tooth disease type 1A (CMT1A). However, the sensitivity of the CMTNS for measuring disease severity and progression in CMT1A patients has been questioned. Here, we applied a Rasch analysis in a French cohort of patients to evaluate the psychometrical properties of the CMTNS. Overall, our analysis supports the validity of the CMTNS for application to CMT1A patients though with some limitations such as certain items of the CMTNS being more suitable for moderate to severe forms of the disease, and some items being disordered. We suggest that additional items and/or categories be considered to better assess mild-to-moderate patients

Look at the time: diel variation in the flight initiation distance of a nectarivorous bird

Abstract: When approached by a predator, foraging animals should adjust escape behavior based on their current energetic status to minimize opportunity costs (foraging time) and maximize the chance of escape. Animals should therefore be more reluctant to leave a foraging patch when their energy reserves are low and should flee using low-energy escape tactics, but be quicker to flee and use the best escape tactic when satiated. Nectarivorous birds have little capacity for energy storage; thus, they should be particularly sensitive to variation in nutritional status throughout the day. We tested whether New Holland honeyeaters (Phylidonyris novaehollandiae) alter their antipredator behavior by testing whether flight initiation distance (FID—the distance at which an individual flees from an approaching predator) and escape tactic (hopping or flying) vary over the course of the day. Honeyeater FID was shortest in the morning, following the overnight fast, and longest at midday. In the evening, though FID tended to shorten, responses were more variable overall, likely due to individual variation in foraging success. In the morning, honeyeaters were equally likely to hop or fly when approached, but increasingly favored flight as the day progressed. These results suggest a strong link between individual energetic condition and antipredator responses. We suggest that time of day is a useful and important variable influencing escape behavior, the potential effects of which should be more consistently considered as a covariate in the widely used FID protocol. Significance statement: Diel variation in internal and external conditions can alter behavioral responses. In this study, we observed antipredator response behaviors in foraging New Holland honeyeaters, small passerines sensitive to changes in energy status throughout the day. We found that honeyeaters allowed researchers to approach more closely in the morning and evening before fleeing and escaped by flying more often than hopping as the day progressed. Our results suggest that antipredator behaviors are sensitive to current energy status and impending energy needs. In addition, we show that time of day is an important consideration in the experimental design and statistical analysis of behavior studies