In the current study, the pharmacodynamics of norhydrocodone were evaluated and compared with hydrocodone and hydromorphone. Binding studies established that norhydrocodone, similar to hydrocodone and hydromorphone, is a m-selective opioid ligand. In vivo analgesia studies (tail flick) CX-6258 demonstrated that, following subcutaneous, intrathecal, and intracerebroventricular

administration, norhydrocodone produced analgesia. Following subcutaneous administration, norhydrocodone was similar to 70-fold less potent, and hydromorphone was similar to 5.4-fold more potent than hydrocodone in producing analgesia. Following intrathecal administration, norhydrocodone produced a shallow analgesia dose-response curve and maximal effect of 15-45%, whereas hydrocodone and hydromorphone produced dose-dependent analgesia. Intrathecal hydromorphone was similar to 174-fold more potent than intrathecal hydrocodone. Following intracerebroventricular administration, norhydrocodone had similar potency to hydrocodone in producing analgesia, while learn more hydromorphone was similar to 96-fold more potent than hydrocodone. Analgesia induced by the three drugs following subcutaneous, intrathecal, and intracerebroventricular administration was antagonized by subcutaneous naltrexone, confirming that it is opioid receptor-mediated. Subcutaneous norhydrocodone-induced analgesia was completely

blocked by intracerebroventricular naltrexone, indicating that

norhydrocodone-induced analgesia is likely a supraspinal effect. Seizure activity was observed following intrathecal administration of all three drugs. Norhydrocodone and hydromorphone were similar to 3.7 to 4.6-fold more potent than hydrocodone in inducing seizure activity. Naltrexone did not antagonize Fer-1 opioid-induced seizure activity, suggesting that seizures were not opioid receptor-mediated. Taken together, norhydrocodone is an active metabolite of hydrocodone and may contribute to therapeutic and toxic effects following hydrocodone administration.”
“Ablation of Barrett’s esophagus using Argon plasma coagulation (APC) is usually followed by the formation of a neosquamous epithelium. Investigating simple columnar or stratified squamous epithelium associated cytokeratin and microRNA (miRNA) expression in neo-squamous epithelium could help determine the identity and stability of the neosquamous epithelium.\n\nNine patients underwent ablation of Barrett’s esophagus with APC. Biopsies were collected from Barrett’s esophagus mucosa and proximal normal squamous epithelium before ablation, and from neosquamous and normal squamous epithelium after ablation. Additional esophageal mucosal biopsies from ten nonrefluxing subjects were used as a reference. RNA was extracted and real-time polymerase chain reaction was used to measure the expression of the cytokeratins CK-8 and CK-14 and the microRNAs miR-143 and miR-205.