Timing of Cholecystectomy in Acute Cholecystitis

Background

Cholecystitis is an inflammation of the gallbladder that most commonly occurs as a result of obstruction of the cystic duct by gallstones. The current standard of treatment for acute cholecystitis is cholecystectomy.

Challenges for opioid receptor nomenclature: IUPHAR Review 9

Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities

Several studies suggest that heteromerization between μ (MOP) and δ (DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β-arrestin-mediated signalling in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identification of a MOP-DOP receptor heteromer-biased agonist that activates both G protein-mediated and β-arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize findings regarding the biological and functional characteristics of the MOP-DOP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

Barrett's esophagus. Characterization and monitoring policy

The authors review the literature about the assessment of risks of adenocarcinoma occurring over the natural history of Barrett's oesophagus with an incidence much higher than in the general population. The best marker is histological analysis of the cylindric epithelium for signs of dysplasia or early carcinoma. Although there is much controversy about the practical benefit of regular surveillance, the authors recommend a yearly endoscopy with multiple site biopsies. With the new potent drugs aimed at controlling gastro-oesophageal reflux, regression of metaplasia might occur, as the authors have observed in 3 patients treated by 60 mg omeprazole. However, prospective studies are needed to confirm this finding and its possible effect on reducing the risk of adenocarcinoma.     

Endoscopic implantation of a biopolymer in the lower esophageal sphincter for gastroesophageal reflux: a pilot study

BACKGROUND: GERD is the most frequent disorder of the esophagus. Endoscopic minimally invasive treatment is desirable. However, the results of injection techniques have been disappointing. METHODS: A pilot study was conducted in patients with GERD, who required continuous therapy with a proton pump inhibitor, in which ethylene-vinyl-alcohol was injected into the muscle of the gastric cardia. Primary endpoints were the safety of the procedure, the effect on lower esophageal sphincter pressure and the stability of the injected material. A secondary endpoint was the effect on heartburn score after discontinuation of treatment with a proton pump inhibitor. RESULTS: Ethylene-vinyl-alcohol injection into the cardia resulted in circular diffusion of the product in 10 of 15 cases, suggesting that implantation into the muscle is feasible. Lower esophageal sphincter pressure was increased in 13 of 15 cases at 1 month and was sustained at a median follow-up of 6 months (range 4-12 months). Mean plus minus SEM of lower esophageal sphincter pressures (15 patients) were 12.2 plus minus 0.9, 18.7 plus minus 1.5 (p = 0.001 at baseline), and 16.7 plus minus 1.3 mm Hg (p = 0.038 from baseline) at, respectively, baseline, 1 month follow-up, and final follow-up. There was also a sustained reduction in heartburn score (off proton pump inhibitor) (3.40 plus minus 0.13 vs. 1.53 plus minus 0.24 and 1.87 plus minus 0.26 at baseline vs. 1 month and final follow-up, respectively; p < 0.01). Nine of the 15 patients had more than 50% of the injected material in place at second follow-up (at 6 months for 8 patients; at 12 months for 1 patient). In only 2 patients was there loss of more than 75% of injected ethylene-vinyl-alcohol. Persistence of greater than 50% of the material was associated with achievement of a circular injection. Only 4 patients had to resume therapy with a proton pump inhibitor. Mild retrosternal discomfort was observed in 8 patients; this disappeared in all cases after a maximum of 3 days. CONCLUSIONS: Ethylene-vinyl-alcohol implantation in the muscle of the cardia is feasible and safe. It leads to a sustained increase in resting lower esophageal sphincter pressure. This is associated with a sustained improvement in heartburn score for patients who previously required continuous therapy with a proton pump inhibitor.