In contrast, deletion of

ACE2 resulted in a fourfold increase in the ratio of intrarenal Any II/Ang 1-7 in the UUO nephropathy. These changes were associated with the development of more intensive tubulointerstitial fibrosis (alpha-SMA, collagen 4SC-202 datasheet I) and inflammation (TNF-alpha, IL-1 beta, MCP-1, F4/80(+) cells, and CD3(+)T cells) in Ace2(-/y) mice at day 3 (all P < 0.05) after UUO, becoming more profound at day 7 (all P < 0.01). Enhanced renal fibrosis and inflammation in the UUO kidney of Ace2(-/y) mice were largely attributed to a marked increase in the intrarenal Ang II signaling (AT1-ERK1/2 mitogen-activated protein kinase), TGF-beta/Smad2/3, and NF-kappa B signaling pathways. Further studies revealed that enhanced TGF-beta/Smad and NE-kappa B signaling in the UUO kidney of Ace2(-/y) mice was associated with upregulation of an E3 ligase Smurf2 and a loss of renal Smad7. In conclusion, enhanced Any II-mediated TGE-beta/Smad and NE-kappa B signaling may be the mechanisms by which loss of Ace2 enhances renal fibrosis and inflammation. Smad7 ubiquitin HDAC inhibitor degradation mediated by Smurf2 may be a central mechanism by which Ace2(-/y) mice promote TGF-beta/Smad2/3-mediated renal fibrosis and NE-kappa B-driven renal inflammation in

a mouse model of UUO nephropathy. Laboratory Investigation (2012) 92, 650-661; doi:10.1038/labinvest.2012.2; published online 13 February 2012″
“Background: Cocaine-induced psychosis (CIP) is among the most

serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the involvement of BDNF in CIP are lacking. Methods: A total of 22 cocaine-dependent patients (aged 33.65 +/- 6.85) who had never experienced psychotic symptoms under the influence of cocaine (non-CIP) and 18 patients (aged 34.18 +/- 8.54) with a history of CIP completed a 2-week detoxification program in an inpatient facility. Two serum samples were collected from each patient at baseline and at the end of the protocol. Demographic, consumption and Idelalisib cell line clinical data were recorded for all patients. A paired group of healthy controls was also included. Results: At the beginning of the detoxification treatment, serum BDNF levels were similar in both the non-CIP and the CIP groups. During early abstinence, the non-CIP group exhibited a significant increase in serum BDNF levels (p = 0.030), whereas the CIP group exhibited a decrease. Improvements in depression (Beck Depression Inventory, BDI, p = 0.003) and withdrawal symptoms (Cocaine Selective Severity Assessment, CSSA, p = 0.013) show a significant positive correlation with serum BDNF levels in the non-CIP group, whereas no correlation between the same variables was found in the CIP group.