These results demonstrate that: i) the COX-2/PGE(2) pathway facilitates epileptiform bursting; and ii) SRIF exerts an anti-epileptic role by coupling to the COX-2/PGE(2) pathway. Selleckchem ICG-001 In conclusion, we have identified a key set of signalling events that underlie anti-convulsant effects of SRIF in a mouse model of hippocampal bursting, thus

providing useful data not only to identify alternative intervention points for the modulation of SRIF function, but also to exploit new chemical space for drug-like molecules. (C) 2008 Elsevier Ltd. All rights reserved.”
“The mechanisms underlying 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonergic (5-HT) toxicity remain unclear. It has been suggested that MDMA depletes 5-HT by increasing brain tyrosine levels, which via non-enzymatic hydroxylation leads to DA-derived free radical formation. Because this hypothesis assumes the pre-existence of hydroxyl radicals, we hypothesized that MDMA metabolism into pro-oxidant compounds is the limiting step in this process. Acute hyperthermia, plasma tyrosine levels and concentrations of MDMA and its main metabolites were higher after a toxic (15 mg/kg i.p.) vs. a non-toxic dose of MDMA (7.5 mg/kg i.p.). The administration

https://www.selleckchem.com/products/kpt-330.html of a non-toxic dose of MDMA in combination with L-tyrosine (0.2 mmol/kg i.p.) produced a similar increase in serum tyrosine levels to those found after a toxic dose of MDMA; however, brain 5-HT content remained unchanged. The non-toxic dose of MDMA combined with a high dose of tyrosine (0.5 mmol/kg i.p.), caused long-term 5-HT depletions in rats treated at 21.5 degrees C but not in those treated at 15 degrees C, conditions known to decrease MDMA metabolism. Furthermore, striatal perfusion of MDMA (100 mu M for 5 h) combined with tyrosine (0.5 mmol/kg i.p.) in hyperthermic rats did not cause see more 5-HT depletions. By contrast,

rats treated with the non-toxic dose of MDMA under heating conditions or combined with entacapone or acivicin, which interfere with MDMA metabolism or increase brain MDMA metabolite availability respectively, showed significant reductions of brain 5-HT content. Altogether, these data indicate that although tyrosine may contribute to MDMA-induced toxicity, MDMA metabolism appears to be the limiting step. (C) 2008 Elsevier Ltd. All rights reserved.”
“Purpose: The feasibility of histotripsy (transcutaneous nonthermal mechanical tissue fractionation) was previously demonstrated in an in vivo rabbit renal cortex model. We explored the spectrum of histotripsy bio-effects on different tissue types in an in vitro porcine kidney model.

Materials and Methods: Using an 18 element focused annular array ultrasound system we performed histotripsy treatments in 5 in vitro porcine kidneys, targeting 7 cortical volumes and 17 tissue volumes bridging the cortex, medulla and/or collecting system. Treated areas were observed using ultrasound.