Nociceptin/orphanin FQ – NOP receptor system: novel genetic and pharmacological tools

The neuropeptide nociceptin/orphanin FQ (N/OFQ) selectively binds and activates the N/OFQ peptide (NOP) receptor. In cells expressing the NOP receptor N/OFQ inhibits cAMP accumulation and Ca2+ conductance and stimulates K+ currents. Via these mechanisms N/OFQ regulates several biological functions in the central nervous system (pain, locomotion, memory, emotional responses, food intake), as well as in the periphery (airways, cardiovascular, genitourinary and gastrointestinal systems). Several research tools including knockout mice and NOP selective agonists and antagonists have been developed in the past and used to investigate the role played by this peptidergic system in pathophysiology and to identify possible therapeutic indications of NOP receptor ligands. The aim of the present study was to make available to the scientific community novel genetic and pharmacological tools to speed up the process of target validation of the NOP receptor. Knockout rats for the NOP receptor gene (NOP(-/-)) have been recently generated. These animals were used in the present study to investigate their emotional (open field, elevated plus maze, and forced swimming test), locomotor (drag and rotarod test), and nociceptive (plantar and formalin test) phenotype in comparison to NOP(+/+) littermates. The results were in line with previous findings obtained with selective NOP receptor antagonists in mice and rats and with mouse knockout studies and indicated that the blockage of N/OFQergic signalling elicits antidepressant and motor stimulant effects. A detailed pharmacological characterization of novel NOP receptor non peptide ligands has been performed. The compound GF-4 displayed high affinity and potency at recombinant human NOP receptor associated with pure antagonist properties. This profile was confirmed in N/OFQ sensitive animal tissues. In vivo GF-4 elicited, similar to other NOP antagonists, beneficial effects in animal models of Parkinson disease. The NOP non-peptide agonists Ro 65-6570, SCH 221510 and compound 6d were characterized in vitro using a calcium mobilization assay and electrically stimulated mouse and rat vas deferens tissues. The results of these studies demonstrated that Ro 65-6570 and SCH-221510 behaved as full agonists showing however some level of NOP selectivity in rat, but not mouse, tissues. Compound 6d did not display NOP selectivity. Finally, mixed NOP/MOP receptor agonists were generated. [Dmt1]N/OFQ(1-13)NH2 was selected as the most potent compound. The mixed NOP/MOP full agonist activity and high affinity of [Dmt1]N/OFQ(1- 13)NH2 was confirmed at human recombinant receptors in receptor and [35S]GTPgS binding studies, at rat spinal cord receptors in [35S]GTPgS binding experiments, and at guinea pig receptors inhibiting neurogenic contractions in the ileum. In vivo in the mouse tail withdrawal assay in mice [Dmt1]N/OFQ(1-13)NH2 was also able to elicit a robust antinociceptive effect being more potent than N/OFQ (by 30 fold) and morphine (by 3 fold). The antinociceptive properties of spinal [Dmt1]N/OFQ(1-13)NH2 were confirmed in non human primate studies. Collectively these results demonstrate that [Dmt1]N/OFQ(1-13)NH2 behaves as mixed NOP/MOP agonist and susbtantiate the suggestion that such mixed ligands are worthy of development as innovative spinal analgesics

Case study: evaluating performance outcomes of a technology change management initiative in a health care organization

The purpose of this research was to examine a case study by evaluating performance outcomes of a technology change management initiative in a health care organization. This study was developed with an array of issues surrounding change management programs with technology platforms, the management of complex change and the amount of criticism that became the impetus behind the implementation of the Electronic Health Records Management Systems (EHRMS) across the healthcare industry and its long-term transformative effects. Despite recognition that user response largely determined the success of a technology implementation or change management program and the fact significant resources are spent on strategic programs to promote acceptance, there was very little research in terms of evaluating performance outcomes which make a change management program more successful in health care settings. The study was challenging and the findings were inconclusive for the research questions. However, the qualitative data gathered from the comments/recommendations section of the eCare Research Survey provided additional information in great detail concerning the research topic. The capture of detailed opinions, attitudes, beliefs and comments/recommendations expressed by the respondents provided suggestions for revisions of the eCare change management program. This qualitative data also provided implications for future research in the field of change management

The BG News January 30, 2006

The BGSU campus student newspaper January 30, 2006. Volume 96 - Issue 89https://scholarworks.bgsu.edu/bg-news/8546/thumbnail.jp

Annual reports of the town officials of Bennington, New Hampshire for the year ended December 31, 2021.

This is an annual report containing vital statistics for a town/city in the state of New Hampshire