PP1 and Fyn siRNA reduced IFN gamma-induced PI3K activity (indicated by decreased phospho-Akt) and the formation of the STAT5b/PI3K(p85 alpha) complex. Collectively, the results suggest the formation of a Fyn-dependent STAT5b/Gab2/PI3K complex that
links IFN gamma to PI3K signalling and the regulation of macromolecular permeability in a model enteric epithelium. Laboratory Investigation (2011) 91, 764-777; doi:10.1038/labinvest.2010.208; published online 14 February 2011″
“Objective: Oral mucositis is a severe, dose-limiting side effect of radio(chemo)therapy for head and neck tumors. The LGX818 epithelial radiation response (ulceration) is accompanied by inflammatory changes. Their interaction with the epithelial processes remains unclear. The present study was initiated to determine the effect of inhibition of TNF-alpha or COX-2 on the epithelial radiation response in the mouse tongue model.\n\nMethods: Daily fractionated irradiation was given with 5 x 3 Gy/week over one (days 0-4) or two weeks (days 0-4, 7-11). Each protocol was terminated by graded test doses (5 dose groups, 10 animals each) to a defined area of the lower tongue surface to generate full dose-effect curves for mucosal ulceration. A TNF-alpha inhibiting antibody (Infliximab) or a COX-2 inhibitor (Celecoxib) was administered.\n\nResults:
click here No effect of Infliximab or Celecoxib was found in any of the protocols. Isoeffective doses for ulcer induction were unchanged. Also, the time course of the response was largely unaffected.\n\nConclusions: Inhibition of TNF-alpha or COX-2, two dominating inflammatory pathways, did not result in modulation of the response of oral epithelium during fractionated irradiation. This suggests that the inflammatory changes mediated through TNF-alpha or COX-2 are not relevant for the epithelial radiation response of oral mucosa. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 472-476″
“An increasing number of studies have evaluated
the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has Stattic mouse been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-field task. The activity of HDAC was evaluated in amygdala, striatum, prefrontal, and hippocampus of animals. The microinjection of SB and VPA in the ventricle, amygdala, striatum, and prefrontal, but not in hippocampus blocked the hyperactivity induced by m-AMPH.