This was associated with a lower muscle triglyceride content and higher AKT phosphorylation. Pair-feeding showed that mitochondrial effects of ghrelin are independent of changes in food intake, whereas combined ghrelin treatment and higher food intake were needed to enhance AKT phosphorylation. Thus, ghrelin-induced muscle mitochondrial changes and lower tissue triglycerides could favor insulin action and muscle anabolism in the presence of improvement in food intake.
Our study shows that combined effects of ghrelin on appetite and muscle mitochondria improve muscle metabolic and nutritional alterations in chronic kidney disease. This could have potential beneficial impact on patient morbidity and survival. Kidney International (2010) 77, 23-28; doi:10.1038/ki.2009.411; IPI-549 published online PLX4032 4 November 2009″
“Introduction: The serotonergic system, especially the 5-HT2A receptor, is involved in various diseases and conditions. It is a very interesting target for medicinal applications.
Methods: Two novel 5-HT2A tracers, namely, [F-18]DD-1 and the enantiomeric pure (R)-[F-18]MH.MZ, were radiolabeled by F-18-fluoroalkylation of the corresponding
desmethyl analogue. In vitro binding autoradiography on rat brain slices was performed to test the affinity and selectivity of these tracers. Moreover, first mu PET experiments of (R)-[F-18]MH.MZ were carried out in Sprague-Dawley rats.
Results: [F-18]DD-1 (K-i=3.23 nM) and (R)-[F-18]MH.MZ (K-i=0.72 nM) were F-18-fluoroalkylated by the secondary synthon [F-18]FETos in a radiochemical yield (RCY) of >70%. The final formulation for both tracers took no longer than 100 min with an overall RCY of similar to 40%. It provided [F-18]tracers with a purity >96% and a typical specific activity of 25-35 GBq/mu mol. Autoradiographic images of (R)-[F-18]MH.MZ (5) and [F-18]DD-1 (4) showed excellent visualization and selectivity of the 5-HT2A receptor for (R)-[F-18]MH.MZ and less specific binding for [F-18]DD-1. The binding potential (BP) of (R)-[F-18]MH.MZ
was determined to be 2.6 in the frontal cortex and 2.2 in the cortex (n=4), www.selleck.cn/products/blebbistatin.html whereas the cortex-to-cerebellum ratio was determined to be 3.2 at steady state (n=4). Cortex-to-cerebellum ratios of (R)-[F-18]MH.MZ were almost twice as much as compared with the racemic [F-18]MH.MZ. Thereby, equal levels of specific activities were used. High uptake could be demonstrated in cortex regions.
Conclusion: Labeling of both novel tracers was carried out in high RCY. Autoradiography revealed (R)-[F-18]MH.MZ as a very selective and affine 5-HT2A tracer (K-i=0.72 nM), whereas [F-18]DD-1 showed no reasonable distribution pattern on autoradiographic sections. Moreover, results from mu PET scans of (R)-[F-18]MH.MZ hint on improved molecular imaging characteristics compared with those of [F-18]MH.MZ. Therefore, (R)-[F-18]MH.MZ appears to be a highly potent and selective serotonergic PET ligand in small animals.