No abstract

Our data suggest that the CYP3A4 and CYP3A5 polymorphisms are unlikely to influence donepezil metabolism and/or clinical outcome. On the other hand, the ABCB1 polymorphisms may play a role in donepezil disposition and clinical outcome.

Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. “Exerkine” has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving the way for both physiological novel insights and potential medical strategies. The five exerkines identified all play a significant role in the healthy effect of exercise. Specifically: miR-1192, released by muscles and myocardium into circulation, by modulating cardioprotective effect in trained mice; miR-342-5p, located into exosomes from vascular endothelial cells, also a cardioprotective miRNA in trained young humans; apelin, released by muscles into circulation, involved in anti-inflammatory pathways and muscle regenerative capacity in rats; GDF-15, released into circulation from yet unknown source, whose effects can be observed on multiple organs in young men after a single bout of exercise; oxytocin, released by myoblasts and myotubes, with autocrine and paracrine functions in myotubes. The systemic transport by vesicles and the crosstalk between distant organs deserve a deep investigation. Sources, targets, transport mechanisms, biological roles, population samples, frequency, intensity, time and type of exercise should be considered for the characterization of existing and novel exerkines. The “exercise is medicine” framework should include exerkines in favor of novel insights for public health.

Altitude hypoxia induces changes in iron homeostasis with serum ferritin (sFER) response being recently linked to erythropoiesis. The main aim of this study was to investigate sFER and Vitamin D (Vit D) response to hypobaric hypoxia, taking into account factors including nutrition and ethnic origin. As part of a "Kanchenjunga Exploration & Physiology" project, 6 Italian trekkers and 6 Nepalese porters took part in a 19-days long altitude trek in the Himalayas self-recording daily food consumption. Blood samples were collected and analyzed before and after the trek for sFER and Vit D. A webbased system calculated the dietary intake, generating reports that were used for later statistical analyses. sFER decreased after the trek (on average by 26% p = 0.013, partial η 2 = 0.479) in both groups, whereas Vit D did not change in both groups. Nepalese tended to have lower sFER, but this difference was reduced when corrected for the dietary intake. Mean Cell Volume (MCV) and Hematocrit (HCT), in respect to baseline, remained higher 10 days after the trek (respectively, 87.37-88.85 fL with p = 0.044, and 43.05-44.63% with p = 0.065) in Italian trekkers. The observed reduction of sFER levels was related to altitude per se as inflammation or anemia were medically excluded. sFER, therefore, may act as a primary factor in the examination of hypobaric hypoxia in field studies. The results of this study open a new door into the mechanisms of iron homeostasis in specific tissues related to hypoxia adaptations, taking into account dietary intake and ethnic origin.