Electrical and structural remodelling in female athlete's heart: A comparative study in women vs men athletes and controls.

BACKGROUND: Athlete's heart is associated with physiological electrical and structural remodelling. Despite the plethora of data published on male athletes, solid data derived from female athletes, compared to male counterparts or sedentary women, are still scarce. OBJECTIVES: We aimed to analyze the electrical, structural, and functional characteristics of athlete's heart in female and male athletes vs sedentary controls. METHODS: Olympic athletes and sedentary controls were evaluated by resting ECG and echocardiography. Athletes were divided into 4 different sports groups. RESULTS: The study population included 1096 individuals (360 female athletes, 410 male athletes, 130 sedentary women and 196 sedentary men). Female athletes had lower resting heart rate, longer PR interval, higher voltage of R, and T waves and more frequently incomplete RBBB, left ventricular (LV) hypertrophy, early repolarization, and anterior T-wave inversion as compared to controls. Biventricular cavity dimensions and LV wall thickness were greater in female athletes than in female controls. However, women showed a lower degree of training-induced structural remodelling than men. In female athletes, both cavity dimensions and LV wall thickness increased from those engaged in skill and power to mixed and endurance disciplines. However, in female athletes, contrary to males, the ECG changes were not significantly different according to the different types of sport discipline. CONCLUSIONS: Highly-trained women demonstrate relevant training-induced electrical and structural remodelling. However, the type of sport did not influence ECG parameters in women, contrary to men, while it impacted biventricular morphologic remodelling, with endurance athletes showing the greatest degree of adaptation.

Identification of the First Synthetic Allosteric Modulator of the CB2 Receptors and Evidence of Its Efficacy for Neuropathic Pain Relief.

The direct activation of cannabinoid receptors (CBRs) results in several beneficial effects; therefore several CBRs ligands have been synthesized and tested in vitro and in vivo. However, none of them reached an advanced phase of clinical development due mainly to side effects on the CNS. Medicinal chemistry approaches are now engaged to develop allosteric modulators that might offer a novel therapeutic approach to achieve potential therapeutic benefits avoiding inherent side effects of orthosteric ligands. Here we identify the first ever synthesized positive allosteric modulator (PAM) that targets CB2Rs. The evidence for this was obtained using [3H]CP55940 and [35S]GTPγS binding assays. This finding will be useful for the characterization of allosteric binding site(s) on CB2Rs which will be essential for the further development of CB2R allosteric modulators. Moreover, the new CB2R PAM displayed antinociceptive activity in vivo in an experimental mouse model of neuropathic pain, raising the possibility that it might be a good candidate for clinical development.