cholecystokinin and Colitis--Ulcerative

Topics: Bradykinin; Cecum; Cholecystokinin; Colitis, Ulcerative; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Diverticulum, Colon; Gastrins; Gastrointestinal Motility; Humans; Muscle Contraction; Parasympathomimetics; Prostaglandins; Radiography; Rectum; Serotonin

Gastric emptying (GE) is delayed in a subset of patients with inflammatory bowel disease (IBD). We have shown before that altered release of gastrointestinal hormones may contribute to GE disturbances, but overall effects of disease activity remain unclear. Thus, we aimed to evaluate GE in patients with IBD during active disease and following therapy.. A total of 20 healthy subjects (HC) and 26 patients with IBD hospitalized because of an acute episode of their disease (Crohn's disease (CD) n = 13, ulcerative colitis (UC) n = 13) underwent a standardized (13) C-octanoic acid GE breath test (baseline test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured periodically throughout the test. A total of 16 patients underwent a second GE test after 3-4 months of therapy.. At baseline, nine patients with IBD had pathologically delayed GE half-time (T½ > 150 min) (P = 0·028 vs. HC). Moreover, T½ was significantly longer in the total group of patients with IBD than in HC (129 ± 12 min vs. 96 ± 7, P = 0·030). Postprandial GLP-1 responses were elevated in IBD (P = 0·002 vs. HC) and correlated with T½ (P = 0·05). Following therapy clinical activity indices and T½ were decreased in IBD (P ≤ 0·01 vs. baseline), and T½ no longer differed from HC (P > 0·5). Moreover, GLP-1 plasma levels decreased significantly (P = 0·031).. Higher disease activity in IBD is associated with prolonged GE and increased release of GLP-1. Following effective therapy, GE is accelerated and GLP-1 release decreases significantly. Thus, increased release of GLP-1 from the inflamed mucosa might contribute to GE disturbances in IBD.

Topics: Adolescent; Adult; Aged; Blood Glucose; Breath Tests; Case-Control Studies; Cholecystokinin; Colitis, Ulcerative; Crohn Disease; Female; Gastric Emptying; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Peptide YY; Postprandial Period; Young Adult

It is unclear why patients with inflammation of the distal bowel complain of symptoms referable to the upper gastrointestinal tract, specifically to gastric emptying (GE) disturbances. Thus we aimed to determine occurrence and putative pathomechanisms of gastric motor disorders in such patients. Thirteen healthy subjects (CON), 13 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 7 with diverticulitis (DIV) underwent a standardized (13)C-octanoic acid gastric emptying breath test. Plasma glucose, CCK, peptide YY, and glucagon-like peptide-1 (GLP-1) were measured periodically and correlated with GE parameters. Results were given in means +/- SD. Compared with CON, GE half time (T) was prolonged by 50% in CD (115 +/- 55 vs. 182 +/- 95 min, P = 0.037). Six CD, 2 DIV, and 2 UC patients had pathological T (>200 min). Postprandial plasma glucose was increased in all patients but was highest in DIV and correlated with T (r = 0.90, P = 0.006). In CD, mean postprandial CCK levels were increased threefold compared with CON (6.5 +/- 6.7 vs. 2.1 +/- 0.6 pmol/l, P = 0.027) and were correlated with T (r = 0.60, P = 0.041). Compared with CON, GLP-1 levels were increased in UC (25.1 +/- 5.2 vs. 33.5 +/- 13.0 pmol/l, P = 0.046) but markedly decreased in DIV (9.6 +/- 5.2 pmol/l, P < 0.0001). We concluded that a subset of patients with CD, UC, or DIV has delayed GE. GE disturbances are most pronounced in CD and might partly be caused by excessive CCK release. In DIV there might be a pathophysiological link between decreased GLP-1 release, postprandial hyperglycemia, and delayed GE. These explorative data encourage further studies in larger patient groups.

Topics: Acute Disease; Adult; Aged; Blood Glucose; C-Reactive Protein; Cholecystokinin; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Diverticulitis, Colonic; Fasting; Female; Gastric Emptying; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Peptide YY; Postprandial Period; Steroids; Young Adult

Ulcerative colitis is associated with altered contractile activity and transit time of colon. On the other hand, cholecystokinin (CCK) has been shown to play an important role in regulation of gastrointestinal motor function including colonic contraction and transit. In the present study, an attempt was made to study the effect of proglumide, a CCK receptor antagonist on experimental colitis in rats. Experimental colitis was induced in male Sprague-Dawley rats by instilling 1 ml of 4% acetic acid followed by flushing with 0.5 ml air. The rats were kept in a head-down position for 30s. Finally, each rat received 1.5 ml colonic wash with 1.5 ml saline. Four groups of rats received proglumide orally (0, 250, 500 and 1000mg/kg). The first dose of proglumide was given 1 h before acetic acid challenge, whereas the second dose of proglumide was given 25 h after the first dose. Sham control rats received an equal volume of saline instead of acetic acid. Forty-eight hours after the acetic acid challenge, the colon was removed, weighed and split longitudinally and scored for injury. Part of the colon was used for histopathological study as well as analysis of myeloperoxidase (MPO) activity (as a marker of neutrophil activity). Acetic acid produced severe diarrhea and exfoliation of the colonic epithelium accompanied by extensive destruction of the mucosal interstitium. Proglumide dose dependently protected rats against acetic acid-induced increase in colon weight, diarrhea, MPO activity and colonic injury. Inhibition of CCK exerts a beneficial effect in experimental colitis. Further studies are warranted to determine the mechanism of protection and the therapeutic potential of CCK inhibitors.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Cholecystokinin; Colitis, Ulcerative; Disease Models, Animal; Dose-Response Relationship, Drug; Indicators and Reagents; Male; Peroxidase; Proglumide; Rats; Rats, Sprague-Dawley

During total parenteral nutrition, gallbladder motility is impaired, resulting in sludge and stone formation. Little is known about gallbladder motility during prolonged enteral nutrition.. We studied gallbladder motility during continuous enteral nutrition (CEN) in nine hospitalized patients with active inflammatory bowel disease. The patients received a polymeric diet (2000 kcal/24 h) by CEN through a nasogastric tube for a prolonged period. Gallbladder volumes were obtained daily by ultrasonography, starting from day 0 (before CEN) and on 7 consecutive days during CEN. At days 0, 1, 4, and 7, the gallbladder response to i.v. cholecystokinin (CCK-33; 0.5 Ivy Dog unit/kg/h) was studied. Plasma CCK levels were determined at regular intervals by radioimmunoassay.. No significant differences were observed on day 0 between patients and a group of nine healthy control subjects in fasting gallbladder volumes (19.4 +/- 2.3 and 19.6 +/- 2.4 cm3, respectively) and gallbladder contraction during CCK infusion (56 +/- 14% and 69 +/- 7%, respectively). During CEN, from day 1 to day 7, mean gallbladder volume remained significantly (p < 0.05) reduced compared with fasting gallbladder volume, and mean plasma CCK levels remained significantly (p < 0.05) increased compared with fasting levels. Although gallbladder volume was significantly reduced during CEN, the gallbladder contractile response to CCK was not affected; at days 1, 4, and 7, gallbladder contraction was 36-57%.. During CEN, 1) gallbladder volume is significantly reduced and plasma CCK levels are significantly increased, 2) these effects are sustained over time (7 days), and 3) the gallbladder remains responsive to exogenous CCK. These results indicate that gallbladder contractility and gallbladder responsiveness to CCK are preserved during prolonged CEN in patients with inflammatory bowel disease.

Topics: Adult; Cholecystokinin; Colitis, Ulcerative; Crohn Disease; Energy Intake; Fasting; Female; Follow-Up Studies; Food, Formulated; Gallbladder; Gastrointestinal Agents; Hospitalization; Humans; Infusions, Intravenous; Intubation, Gastrointestinal; Male; Middle Aged; Pancreatic Polypeptide; Parenteral Nutrition, Total; Ultrasonography

Topics: Barium Sulfate; Celiac Disease; Cholecystokinin; Colectomy; Colitis, Ulcerative; Enteritis; Gastrointestinal Motility; Humans; Ileostomy; Intestinal Diseases; Intestine, Small; Radiography

Topics: Arthritis, Rheumatoid; Cholecystokinin; Colitis, Ulcerative; Gastrointestinal Hormones; Humans; Pancreas; Plasmacytoma; Secretin