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Pauwels A.,Catholic University of Leuven | Verleden S.,Catholic University of Leuven | Farre R.,Catholic University of Leuven | Vanaudenaerde B.M.,Catholic University of Leuven | And 7 more authors.
Journal of Cystic Fibrosis | Year: 2013

CF patients are often treated with proton pump inhibitors (PPIs) to reduce acidic gastro-esophageal reflux (GER) and bronchial aspiration of duodeno-gastric contents is common in CF. We have previously demonstrated that gastric juice (GJ) from patients "on" PPI can induce interleukin-8 (IL-8) production by bronchial epithelial cells in culture. We hypothesized that such effect would be more pronounced in CF patients known to have high inflammatory susceptibility. We aimed to evaluate the effect of GJ on IL-8 production by primary bronchial epithelial cells (PBEC), derived from a CF patient and a healthy subject. Methods: PBEC obtained from one donor (normal PBEC) and one receptor (CF-PBEC) for lung transplantation were stimulated with GJ from patients "off" and "on" PPI. IL-8 levels were measured in the supernatant. Results: GJ from patients "on" PPI provoked a significant higher IL-8 production compared to GJ from patients "off" PPI, both in normal PBEC [462 (200-1468) vs. 11 (4-28) pg/ml, p = 0.0001] as in CF-PBEC [1468 (841-2449) vs. 85 (26-131) pg/ml, p < 0.0001]. Exposure of the cells to GJ "off" PPI and "on" PPI provoked significantly higher IL-8 production in the CF-PBEC compared to the normal PBEC ["off" PPI 85 (26-131) vs. 11 (4-28) pg/ml, p = 0.01; "on" PPI 1468 (841-2449) vs. 462 (200-1468) pg/ml, p = 0.01]. Filtration (0.20 μm) of the GJ "on" PPI, to eliminate large particles and bacterial sub-products, resulted in a significant decrease of IL-8 production. Conclusion: Patients with CF, treated with PPIs, have GJ with high pH and high endotoxin levels. These patients often have GER and bronchial aspiration. The aspirated material (GJ "on" PPI) has a significantly enhanced inflammatory effect on CF bronchial epithelial cells in culture. As chronic PPI treatment in CF may result in a paradoxically increased inflammatory effect in the airways, alternative anti-reflux therapies should be considered in CF. © 2013 European Cystic Fibrosis Society. Source


Omran Y.A.,Queen Mary, University of London | Aziz Q.,The Wingate Institute of Neurogastroenterology
Advances in Experimental Medicine and Biology | Year: 2014

The interaction between the brain and the gut has been recognized for many centuries. This bidirectional interaction occurs via neural, immunological and hormonal routes, and is important not only in normal gastrointestinal function but also plays a significant role in shaping higher cognitive function such as our feelings and our subconscious decision-making. Therefore, it remains unsurprising that perturbations in normal signalling have been associated with a multitude of disorders, including inflammatory and functional gastrointestinal disorders, and eating disorders. © Springer New York 2014. Source


Carrington E.V.,The Wingate Institute of Neurogastroenterology | Carrington E.V.,The Surgical Center | Brokjaer A.,The Wingate Institute of Neurogastroenterology | Brokjaer A.,University of Aalborg | And 12 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: High-resolution anorectal manometry (HRAM) is a relatively new method for collection and interpretation of data relevant to sphincteric function, and for the first time allows a global appreciation of the anorectum as a functional unit. Historically, traditional anal manometry has been plagued by lack of standardization and healthy volunteer data of variable quality. The aims of this study were: (i) to obtain normative data sets for traditional measures of anorectal function using HRAM in healthy subjects and; (ii) to qualitatively describe novel physiological phenomena, which may be of future relevance when this method is applied to patients. Methods: 115 healthy subjects (96 female) underwent HRAM using a 10 channel, 12F solid-state catheter. Measurements were performed during rest, squeeze, cough, and simulated defecation (push). Data were displayed as color contour plots and analysed using a commercially available manometric system (Solar GI HRM v9.1, Medical Measurement Systems). Associations between age, gender and parity were subsequently explored. Key Results: HRAM color contour plots provided clear delineation of the high-pressure zone within the anal canal and showed recruitment during maneuvers that altered intra-anal pressures. Automated analysis produced quantitative data, which have been presented on the basis of gender and parity due to the effect of these covariates on some sphincter functions. In line with traditional manometry, some age and gender differences were seen. Males had a greater functional anal canal length and anal pressures during the cough maneuver. Parity in females was associated with reduced squeeze increments. Conclusions & Inferences: The study provides a large healthy volunteer dataset and parameters of traditional measures of anorectal function. A number of novel phenomena are appreciated, the significance of which will require further analysis and comparisons with patient populations. © 2014 John Wiley & Sons Ltd. Source

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