Chemical modifications of nociceptin/orphanin FQ (N/OFQ) peptide that result in increased potency and resistance to degradation have recently lead to the discovery of [(pF)Phe 4 Aib 7 Arg 14 Lys 15 ]N/OFQ-NH 2 (UFP-112), a novel N/OFQ peptide (NOP) receptor agonist. The aim of this study was to investigate the pharmacological profile of intrathecally administered UFP-112 in monkeys under different behavioral assays. Intrathecal UFP-112 (1-10 nmol) dose-dependently produced antinociception against an acute noxious stimulus (50 °C water) and capsaicin-induced thermal hyperalgesia. Intrathecal UFP-112-induced antinociception could be reversed by a NOP receptor antagonist, J-113397 (0.1 mg/kg), but not by a classic opioid receptor antagonist, naltrexone (0.03 mg/kg). Like intrathecal morphine, UFP-112 produced antinociception in two primate pain models with a similar magnitude of effectiveness and a similar duration of action that last for 4-5 h. Unlike intrathecal morphine, UFP-112 did not produce itch/ scratching responses. In addition, intrathecal inactive doses of UFP-112 and morphine produced significant antinociceptive effects when given in combination without increasing scratching responses. These results demonstrated that intrathecal UFP-112 produced long-lasting morphinecomparable antinociceptive effects without potential itch side effect. This study is the first to provide functional evidence that selective NOP receptor agonists such as UFP-112 alone or in conjunction with morphine may improve the quality of spinal analgesia.

Abstract-Evidence exists that protein kinase C and the mammalian target of rapamycin are important regulators of cardiac hypertrophy. We examined the contribution of these signaling kinases to cardiac growth in spontaneously hypertensive rats (SHRs

In microsurgical flap procedures, creation of an arteriovenous fistula (AVF) is a technique of vein grafting where the vein graft is connected to recipient vessels as a flow-through loop prior to harvest and inset of the flap. Controversy exists whether this technique can be used as a 2-stage procedure with the loop and flap transfer accomplished in sequential operations or if the loop and flap transfer should be performed in a single operation. We performed 12 consecutive 1-stage AVF-flap procedures, with 1 flap failure. We combined this series with previously published reports to compare outcomes of 1-stage and 2-stage procedures. We found no significant difference in flap outcomes or complication rates between the 2 strategies. We conclude from our experience and this analysis that single-stage AVF-flap procedures are the optimum application of this technique.