Epacadostat (EPAC) is a first-in-class, orally active inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 and has demonstrated promising clinical activity. In humans, three major plasma metabolites have been identified: M9 (a glucuronide-conjugate), M11 (a gut microbiota metabolite), and M12 (a secondary metabolite formed from M11). It is proposed, based on the human pharmacokinetics of EPAC,...

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean M...

BACKGROUND No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants. METHODS Because remifentanil is rapidly metaboli...

PURPOSE this study examined the effects of heavy resistance training on the relationships between power loss and surface EMG (sEMG) indices and blood metabolite concentrations on dynamic exercise-induced fatigue with the same relative load as in pretraining. METHODS twelve trained subjects performed five sets consisting of 10 repetitions in the leg press, with 2 min of rest between sets befor...

The importance of propionate in intermediary metabolism is generally recognized (1). Reid (2) concludes from his work on sheep that for these animals propionic acid is the chief source of blood glucose. Similarly McClymont (3) suggests that ruminants in general maintain their blood sugar level by gluconeogenesis from propionic acid. Injection of C14-labeled propionate into a cow’s blood stream ...