Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells

This is the accepted version of the following article: [Raghupathi, R., Duffield, M. D., Zelkas, L., Meedeniya, A., Brookes, S. J. H., Sia, T. C., Wattchow, D. A., Spencer, N. J. and Keating, D. J. (2013), Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells. The Journal of Physiology, 591: 5959–5975. doi: 10.1113/jphysiol.2013.259796], which has been published in final form at [http://dx.doi.org/10.1113/jphysiol.2013.259796]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery

Use of guideline-recommended adjuvant therapies and survival outcomes for people with colorectal cancer at tertiary referral hospitals in South Australia

Rationale, aims and objectives: Adjuvant care for colorectal cancer (CRC) has increased over the past 3 decades in South Australia (SA) in accordance with national treatment guidelines. This study explores the (1) receipt of adjuvant therapy for CRC in SA as related to national guideline recommendations, with a focus on stage C colon and stage B and C rectal cancer; (2) timing of these adjuvant therapies in relation to surgery; and (3) comparative survival outcomes. Methods: Data from the SA Clinical Cancer Registry from 4 tertiary referral hospitals for 2000 to 2010 were examined. Patterns of care were compared with treatment guidelines using multivariable logistic regression. Disease‐specific survivals were calculated by treatment pathway. Results: Four hundred forty‐three (60%) patients with stage C colon cancer and 363 (46%) with stage B and C rectal cancer received guideline‐recommended care. While an overall increase in proportion receiving adjuvant care was not evident across the study period, the proportion having neoadjuvant care increased substantially. Older age was an independent predictor of not receiving adjuvant care. Patients with stage C colon cancer who received recommended adjuvant care had a higher 5‐year survival than those not receiving this care, ie, 71.2% vs 53.2%. Similarly adjuvant therapy was associated with better outcomes for stage C rectal cancers. The median time for receiving adjuvant care was 8 weeks. Conclusions: Survival was better for stage C CRC treated according to guidelines. Adjuvant care should be provided except where clear contraindications present. Other possible contributors to guideline adherence warranting additional investigation include co‐morbidity status, multidisciplinary team involvement, and choice.Pamela Adelson, Kellie Fusco, Christos Karapetis, David Wattchow, Rohit Joshi, Timothy Price, Greg Sharplin, David Rode

Contesting authentic practice and ethical authority in adventure tourism

This paper examines the discourses of authenticity and ethics used among adventure tourists regarding the use of the natural environment. In one case, full-time traveling rock climbers use their dedication to the sport and annual visits to the Red River Gorge as evidence for their authoritative voice on ethical climbing practice. While they identify the growing numbers of leisure climbers as a problem for sustainability, many also take up temporary employment as guides and are directly involved in the introduction of new climbers to the area. In another case, two groups of wilderness enthusiasts – “ADK 46ers” and “Summit Stewards” – lament the environmental and social impacts of other recreational users in the Adirondack Park. Despite being visitors themselves, Summit Stewards and 46ers use their sense of place and knowledge of Adirondack history and ecology to substantiate their authority as purveyors of ethical practice. In both cases, senses of responsibility are inspired by senses of place, but are articulated through notions of authenticity and used as justification for ethical authority. While validating their presence in these outdoor spaces, the use of such rhetoric also minimizes their own impacts yielding further tensions among user groups

Discovery and Validation of Molecular Biomarkers for Colorectal Adenomas and Cancer with Application to Blood Testing

BACKGROUND & AIMS: Colorectal cancer incidence and deaths are reduced by the detection and removal of early-stage, treatable neoplasia but we lack proven biomarkers sensitive for both cancer and pre-invasive adenomas. The aims of this study were to determine if adenomas and cancers exhibit characteristic patterns of biomarker expression and to explore whether a tissue-discovered (and validated) biomarker is differentially expressed in the plasma of patients with colorectal adenomas or cancer. METHODS: Candidate RNA biomarkers were identified by oligonucleotide microarray analysis of colorectal specimens (222 normal, 29 adenoma, 161 adenocarcinoma and 50 colitis) and validated in a previously untested cohort of 68 colorectal specimens using a custom-designed oligonucleotide microarray. One validated biomarker, KIAA1199, was assayed using qRT-PCR on plasma extracted RNA from 20 colonoscopy-confirmed healthy controls, 20 patients with adenoma, and 20 with cancer. RESULTS: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers compared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated in independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was selected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an uncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/40) compared to neoplasia-free controls (6/20). CONCLUSIONS: Colorectal neoplasia exhibits characteristic patterns of gene expression. KIAA1199 is differentially expressed in neoplastic tissues and KIAA1199 transcripts are more abundant in the plasma of patients with either cancer or adenoma compared to controls

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events

This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.© 2008 Augestad et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Sugar responses of human enterochromaffin cells depend on gut region, sex, and body mass

Gut-derived serotonin (5-HT) is released from enterochromaffin (EC) cells in response to nutrient cues, and acts to slow gastric emptying and modulate gastric motility. Rodent studies also evidence a role for gut-derived 5-HT in the control of hepatic glucose production, lipolysis and thermogenesis, and in mediating diet-induced obesity. EC cell number and 5-HT content is increased in the small intestine of obese rodents and human, however, it is unknown whether EC cells respond directly to glucose in humans, and whether their capacity to release 5-HT is perturbed in obesity. We therefore investigated 5-HT release from human duodenal and colonic EC cells in response to glucose, sucrose, fructose and α-glucoside (αMG) in relation to body mass index (BMI). EC cells released 5-HT only in response to 100 and 300 mM glucose (duodenum) and 300 mM glucose (colon), independently of osmolarity. Duodenal, but not colonic, EC cells also released 5-HT in response to sucrose and αMG, but did not respond to fructose. 5-HT content was similar in all EC cells in males, and colonic EC cells in females, but 3 to 4-fold higher in duodenal EC cells from overweight females (p < 0.05 compared to lean, obese). Glucose-evoked 5-HT release was 3-fold higher in the duodenum of overweight females (p < 0.05, compared to obese), but absent here in overweight males. Our data demonstrate that primary human EC cells respond directly to dietary glucose cues, with regional differences in selectivity for other sugars. Augmented glucose-evoked 5-HT release from duodenal EC is a feature of overweight females, and may be an early determinant of obesity.Amanda L. Lumsden, Alyce M. Martin, Emily W. Sun, Gudrun Schober, Nicole J. Isaacs, Nektaria Pezos, David A. Wattchow, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L. Due, Christopher K. Rayner, Nam Q. Nguyen, Alice P. Liou, V. Margaret Jackson, Richard L. Young, and Damien J. Keatin