Characterization of the intrinsic and extrinsic innervation of the gall bladder epithelium in the Australian Brush-tailed possum (Trichosurus vulpecula)

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Pain-related gene expression profile during the onset and resolution of caerulein-induced acute pancreatitis in mice

Bazargan M, Hussey DJ, Schloithe AC, Blackshaw LA, Davison JS, Toouli J, Saccone GT

Toward more efficient surveillance of Barrett’s esophagus: identification and exclusion of patients at low risk of cancer

Background: Endoscopic surveillance of Barrett’s esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost-effective surveillance was sought. Methods: The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals. Results: During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2\ua0cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CL

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse

United State

A Method for Increasing the Robustness of Stable Feature Selection for Biomarker Discovery in Molecular Medicine Developed Using Serum Small Extracellular Vesicle Associated miRNAs and the Barrett’s Oesophagus Disease Spectrum

The biomarker development field within molecular medicine remains limited by the methods that are available for building predictive models. We developed an efficient method for conservatively estimating confidence intervals for the cross validation-derived prediction errors of biomarker models. This new method was investigated for its ability to improve the capacity of our previously developed method, StaVarSel, for selecting stable biomarkers. Compared with the standard cross validation method, StaVarSel markedly improved the estimated generalisable predictive capacity of serum miRNA biomarkers for the detection of disease states that are at increased risk of progressing to oesophageal adenocarcinoma. The incorporation of our new method for conservatively estimating confidence intervals into StaVarSel resulted in the selection of less complex models with increased stability and improved or similar predictive capacities. The methods developed in this study have the potential to improve progress from biomarker discovery to biomarker driven translational research

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice

AbstractBackgroundWe have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP.MethodsAcute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured.ResultsGalantide significantly reduced AP-induced hyperenzymaemia by 39–45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28–45%.ConclusionsTreatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action

Sleeve sphincter of Oddi (SO) manometry: a new method for characterizing the motility of the sphincter of Oddi

The original publication can be found at www.springerlink.comBackground/Purpose Perfused multilumen sphincter of Oddi (SO) manometry is accepted as the gold standard for diagnosis of SO dysfunction. However, this technique is associated with a relatively high incidence of post-procedure acute pancreatitis. In addition, triple-lumen manometry recordings may be difficult to interpret, as movement may produce artifacts. We have refined the development of a sleeve sensor for human SO manometry. This assembly aims to overcome the above limitations. In this study the accuracy of sleeve SO manometry (SOM) has been evaluated and compared with standard triple-lumen perfused SOM. Methods Patients undergoing SO manometric studies consented to having both standard triple-lumen and sleeve SOM. A total of 32 paired studies were performed in 29 patients. Diagnosis was made only from standard triple-lumen SOM and the patient treated accordingly. For each study, SO basal pressure, contraction, amplitude, and frequency were recorded. Results There was no statistically significant difference in the recordings of SO basal pressure, contraction, amplitude, and frequency between the two techniques. A strong correlation was demonstrated between SO basal pressure determined with the two catheters. The accuracy of sleeve SOM is comparable to standard triple-lumen SOM, with less movement artifact. One patient developed mild post-manometric pancreatitis. Conclusions The sleeve catheter records SO pressures with comparable values to standard triple-lumen SOM. The sleeve assembly potentially can replace the use of the perfused triple-lumen catheter for the objective diagnosis of SO dysfunction.Masahiko Kawamoto, Joseph Geenen, Taher Omari, Ann C. Schloithe, Gino T. P. Saccone and James Tooul