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Oud-Turnhout, Belgium

Tack J.,Catholic University of Leuven | Feng Y.,Across Health | Schenck F.,Across Health | Specht Gryp R.,Shire Movetis NV
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Data on treatment satisfaction in European men and women with chronic constipation are limited. Aim To assess satisfaction with current treatment among European men and women with chronic constipation. Methods An internet-based survey was conducted in 2009 in 10 European countries: Austria, Germany, France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands. Participants had self-reported chronic constipation (<3 bowel movements/week and ≥1 symptoms for ≥6 months of: pain during defecation; lumpy/hard faeces; and feeling of incomplete evacuation). Demographic data and disease history were collected. For participants using laxatives, drug name/class, satisfaction with treatment and interest in other treatments were collected. Results Of the 1941 participants screened, 1355 had chronic constipation and met the inclusion criteria (chronic constipation population). The majority of the chronic constipation population who disclosed their sex (n = 811) were women (82%). Sixty-eight per cent of respondents (n = 855/1255) reported using laxatives, with the proportion of laxative users differing between subsets. Twenty-eight per cent (n = 225/793) were (very) satisfied with their treatment, whereas 44% (n = 345/793) were neutral and 28% (n = 223/793) (very) dissatisfied. There was no relationship between type of laxative and degree of (dis)satisfaction. Interest in other treatments was high with 83% (n = 686/827) of respondents 'absolutely' or 'probably' interested. Respondents dissatisfied with their treatment were more likely to be interested in other treatments. Conclusions Laxative-use is common for chronic constipation. In this large survey, 28% of participants were dissatisfied with their treatment, with the majority interested in other treatments. © 2012 Blackwell Publishing Ltd.

Loos M.,Ghent University | Hellemans A.,Shire Movetis NV | Cox E.,Ghent University
Veterinary Immunology and Immunopathology | Year: 2013

Enterotoxigenic Escherichia coli (ETEC) are a major cause of infectious diarrhea both in human and pigs. After ingestion of contaminated food or water, ETEC bacteria colonize the small intestine where they produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, which induce watery diarrhea. We investigated the possibility of eliciting STa-induced secretion in jejunal segments of anesthetized pigs using a small-intestinal segment perfusion (SISP) model. Five consecutive mid-jejunal segments of anaesthetized piglets were perfused for 6. h with different concentrations of STa in a physiologic salt solution. Changes in intestinal net fluid absorption were measured. From the results we could conclude that the STa response was dose-dependent and that continuous perfusion with 50. nM of STa or more was required to reduce net absorption. This concentration was sufficient to reduce net absorption compared to control segments in 12 out of 14 piglets. STa-induced responses however showed relative high variation between different jejunal segments of one pig, similar to the inter-segment variation seen in control animals where segments were perfused with physiologic salt solution. These results indicate that more optimization is required before this model could be used to test compounds that could interfere with the STa-induced fluid secretion. © 2012 Elsevier B.V.

Weninger S.,Ghent University | De Maeyer J.H.,Shire Movetis NV | Lefebvre R.A.,Ghent University
Naunyn-Schmiedeberg's Archives of Pharmacology | Year: 2013

Our objective was to investigate the role of phosphodiesterase (PDE)3 and PDE4 and cGMP in the control of cAMP metabolism and of phosphorylation of troponin I (TnI) and phospholamban (PLB) when 5-HT4 receptors are activated in pig left atrium. Electrically paced porcine left atrial muscles, mounted in organ baths, received stimulators of particulate guanylyl cyclase (pGC) or soluble guanylyl cyclase (sGC) and/or specific PDE inhibitors followed by 5-HT or the 5-HT4 receptor agonist prucalopride. Muscles were freeze-clamped at different moments of exposure to measure phosphorylation of the cAMP/protein kinase A targets TnI and PLB by immunoblotting and cAMP levels by enzyme immunoassay. Corresponding with the functional results, 5-HT only transiently increased cAMP content, but caused a less quickly declining phosphorylation of PLB and did not significantly change TnI phosphorylation. Under combined PDE3 and PDE4 inhibition, the 5-HT-induced increase in cAMP levels and PLB phosphorylation was enhanced and sustained, and TnI phosphorylation was now also increased. Responses to prucalopride per se and the influence thereupon of PDE3 and PDE4 inhibition were similar except that responses were generally smaller. Stimulation of pGC together with PDE4 inhibition increased 5-HT-induced PLB phosphorylation compared to 5-HT alone, consistent with functional responses. sGC stimulation hastened the fade of inotropic responses to 5-HT, while cAMP levels were not altered. PDE3 and PDE4 control the cAMP response to 5-HT4 receptor activation, causing a dampening of downstream signalling. Stimulation of pGC is able to enhance inotropic responses to 5-HT by increasing cAMP levels, while sGC stimulation decreases contraction to 5-HT cAMP independently. © 2013 Springer-Verlag Berlin Heidelberg.

Tack J.,University Hospital | Stanghellini V.,University of Bologna | Dubois D.,Free University of Colombia | Joseph A.,Health Economics and Outcomes Research | And 2 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: Prucalopride is a 5-HT4 receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three 12-week, double-blind trials evaluated the effect of prucalopride 2 mg q.d. on common constipation symptoms in women in whom laxatives had failed to provide adequate relief. The effect of prucalopride on bowel function was outside the scope of the analysis and has been described elsewhere. Methods: Women with self-reported inadequate relief from laxatives and included in the prucalopride 2 mg or placebo arm of the trials were selected for analysis. Symptom severity was determined with the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Observed changes from baseline in individual item scores were also evaluated by calculating Cohen's D effect sizes using baseline standard deviation (SD) (>0.2-0.5, >0.5-0.8 and >0.8 for small, moderate and large effects, respectively). Key Results: Data were analyzed for 936 women. The proportion of women with a PAC-SYM severity score >2 at baseline was 50.0% for abdominal symptoms, 71.4% for stool symptoms, and 15.5% for rectal symptoms. Excluding the women without presence of a symptom at baseline from the effect size calculations showed that prucalopride 2 mg had a large effect (>0.8) on all PAC-SYM items, including abdominal pain, abdominal discomfort, bloating, straining, and painful bowel movements. For abdominal symptoms and stool symptoms, effect sizes with prucalopride 2 mg were 1.3-2.3 times larger than those with placebo. Conclusions & Inferences: Prucalopride 2 mg q.d. for 12 weeks alleviates common constipation symptoms in women in whom laxatives had failed to provide adequate relief. © 2013 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd..

Emmanuel A.V.,University College London | Kamm M.A.,St. Vincents Hospital | Kamm M.A.,Imperial College London | Roy A.J.,University College London | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2012

Background Chronic intestinal pseudo-obstruction is a disabling condition for which there are no established drug therapies. The condition is caused by a diverse range of intestinal myopathies and neuropathies. Aim To assess the therapeutic efficacy of prucalopride, a selective high-affinity 5-HT 4 receptor agonist, we employed a multiple n = 1 study design. Each patient acted as his/her own control, each day counting as one treatment episode, allowing comparison of 168 days on each of active drug and placebo. Methods Double-blind, randomised, placebo-controlled, cross-over trial of four 12-week treatment periods, with 2-4 mg prucalopride or placebo daily. In each of the first and second 6 months there was a prucalopride and a placebo treatment. Patients with proven chronic intestinal pseudo-obstruction, including dilated gut, were included. Evaluation was by patient diary and global evaluation. Results Seven patients participated (mean 42 years, five female, median symptom duration 11 years). Three discontinued, two due to study length, and one on prucalopride due to unrelated malnutrition and bronchopneumonia. Four patients (three visceral myopathy and one visceral neuropathy) completed the study; prucalopride significantly improved pain in three of four patients, nausea in two, vomiting in one, bloating in four and analgesic intake. Bowel function was not changed substantially. Conclusions n = 1 studies in rare conditions allow drug efficacy assessment. Prucalopride relieves symptoms in selected patients with chronic pseudo-obstruction. © 2011 Blackwell Publishing Ltd.

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