Here we used patch-clamp buy AG-120 technique in a whole-cell configuration to compare functional activity of 3′-fluoroepibatidine to that of epibatidine by itself on recombinant alpha 4 beta 2, alpha 7 and alpha 3 beta 4 neuronal nAChRs. The agonist effect of (+/-)-epibatidine
was partial and yielded comparable EC(50)s of 0.012 mu M (72% efficacy) and 0.027 mu M (81% efficacy) at alpha 4 beta 2 and alpha 3 beta 4 nAChRs, respectively, but was full at alpha 7 nAChRs with an EC(50) of 4.8 mu M. Testing of the analog at different concentrations revealed that it acts as a full agonist with an EC(50) of 0.36 mu M at alpha 4 beta 2 nAChRs and induces partial agonist effect (66% efficacy) at alpha 7 nAChRs with an EC(50) of 9.8 mu M and an IC(50) corresponding to 225 mu M. In contrast, the analog caused only 24% maximal activation at the range of concentrations from 0.1 to 100 mu M and, in addition, induced ail inhibition of alpha 3 beta 4 nAChR function with an IC(50) of 8.3 mu M. Our functional data, which are in agreement with previous binding and behavioral findings, demonstrate that 3′-fluoro Substitution Selleck SC75741 in the pyridine ring of epibatidine results in an improved pharmacological profile as observed by an increased efficacy and selectivity for alpha 4 beta 2 versus alpha 3 beta 4 nAChRs. (C) 2008 Elsevier Ltd. All rights reserved.”
“Objective:
The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two
techniques.
Methods: The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for subjects undergoing a Norwood procedure with either the right ventricle -pulmonary artery or modified Blalock-Taussig Pitavastatin mouse shunt. Infants with a diagnosis of single, morphologically right ventricle anomaly who are undergoing a Norwood procedure are eligible for inclusion in this study. The primary outcome is death or cardiac transplant 12 months after random assignment. Secondary outcomes include postoperative morbidity after Norwood and stage II palliation procedures, right ventricular function and pulmonary arterial growth at stage II palliation, and neurodevelopmental outcomes at 14 months old. Incidence of adverse events will also be compared between treatment groups.
Conclusion: This study will make an important contribution to the care of patients with hypoplastic left heart syndrome and related forms of single, morphologically right ventricle.
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