Experiments were performed in male Wistar rats under free-feeding and fasting conditions. We measured hypothalamic neuropeptides and monoamines by in situ hybridization and HPLC respectively as well as
plasmatic levels of relevant endocrine signals. OEA administration induced changes in hypothalamic monoaminergic activity and in the anorexigenic neuropeptide CART expressed in the paraventricular nucleus (PVN) but lacked effect on neuropeptides expression in nucleus arcuatus. In addition, OEA induced peripheral changes Batimastat solubility dmso in gut peptides, with marked effects on PYY and Chrelin. These results further suggest that anorexigenic properties of OEA are mediated by peripheral signals and by central alterations in neuropeptides expressed by feeding-involved hypothalamic structures receiving input from peripheral sensory systems, such as the PVN. (C) 2010 Elsevier Ltd. All rights reserved.”
“We prospectively studied the impact of several cytogenetic abnormalities (CAs) in patients with relapsed/refractory myeloma who received lenalidomide and dexamethasone (RD) with or without the addition of bortezomib (V). On
the basis of the presence of previous neuropathy, 50 patients were treated with RD and 49, without preexisting neuropathy, with VRD. The overall response rate was 63%, similar for RD and VRD. Poor risk cytogenetics were associated with lower response rates in RD (P = 0.01), but not in VRD (P = 0.219). The median progression-free survival (PFS) was similar for RD (9 months) and VRD (7 months). PLK inhibitor The median overall survival (OS) for all Apoptosis antagonist patients was 16 months, with no differences between RD or VRD regimens. Poor risk cytogenetics, especially del17p, resistance to previous thalidomide, elevated lactate dehydrogenase (LDH) and presence of extramedullary disease were associated with inferior response to therapy and shorter PFS and OS. The impact of other CAs on OS was
more pronounced in RD. In conclusion, the presence of CAs is an important adverse prognostic factor for patients with relapsed/refractory myeloma, but resistance to previous thalidomide, elevated LDH and presence of extramedullary disease remain of major prognostic importance. The outcome of patients with del17p remains extremely poor even with VRD combination. Leukemia (2010) 24, 1769-1778; doi: 10.1038/leu.2010.175; published online 26 August 2010″
“The function of 5-HT6 receptors, one of the last additions to the large family of 5-HT receptors, is largely unknown due to the limited knowledge of their transduction mechanisms, lack of full centrally acting agonists and inconsistencies in the pharmacological and neurochemical effects of the antagonists. Recently, a new full agonist, ST1936, with nanomolar affinity for 5-HT6 receptors, has become available.