Following escalation of intake, animals received one of two selective CRF1 antagonists: antalarmin (6.3-25 mg/kg, i.p.) or N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5a]pyrimidin-7-amine LY2090314 mouse (MPZP; 3.6-27.5 mg/kg, s.c.).
Results By day 11 of the escalation period, LgA rats increased their cocaine intake, reaching an intake level of 15.1 mg/kg, compared to
11.1 mg/kg in ShA rats, during the first hour of sessions. Antalarmin reduced cocaine self-administration at the highest dose selectively in the LgA group but not the ShA group. MPZP reduced cocaine intake both in LgA and ShA rats. However, MPZP did so at a lower dose in LgA rats than in ShA rats. Within the LgA group, MPZP decreased cocaine intake in the first 10 min (loading phase) as well as in the latter session intake (maintenance phase).
Conclusion The data suggest that hypersensitivity of the CRF system occurs with extended access to cocaine
self-administration and that this altered CRF system may contribute to the increased motivation to self-administer cocaine that develops during psychostimulant dependence.”
“Regulation of protein function by S-nitrosation of critical cysteines is known to be an important mechanism Selleck AZD2281 for nitric oxide signaling. Evidence for this comes from several different experimental approaches including the ascorbate-based biotin switch method. However technical problems with specificity and sensitivity of ascorbate reduction of S-nitrosothiols limit its usefulness and reliability. In the current study we report the use of triphenylphosphine ester derivatives to selectively reduce SNO bonds in proteins. After triphenylphosphine ester reduction, thiols were tagged with biotin or fluorescently labeled maleimide reagents. Importantly
we demonstrate that these compounds are specific reductants of SNO in complex biological samples and do not reduce protein disulfides or protein thiols modified by hydrogen peroxide. Reduction proceeds efficiently CHIR-99021 research buy in cell extracts and in whole fixed cells. Application of this approach allowed us to demonstrate S-nitrosation of specific cellular proteins, label S-nitrosoproteins in whole fixed cells (especially the nuclear compartment) and demonstrate S-nitrosoprotein formation in cells expressing inducible nitric oxide synthase. (C) 2011 Elsevier Inc. All rights reserved.”
“Background: Patients with renal insufficiency (RI) are frequently excluded from trials assessing various endovascular revascularization concepts in critical limb ischemia (CLI) although information on clinical outcomes is scarce.
Methods: Consecutive patients with CLI undergoing endovascular lower limb revascularization during a 4.5-year time interval at a tertiary referral center were prospectively followed over a 12-month period.