The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of P oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens=24 from six patients, p<0*001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the P oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis. (Gut 1995; 36: 93-99)
Previous studies have shown that butyrate is an important energy source for the distal colon, and that its metabolism may be defective in . ulcerative colitis (UC). A (Gut 1993; 34: 1552-1558 of the colonic epithelium. Colitis, which is histologically similar to ulcerative colitis, has also been described in association with pellagra.5 How the various forms of nutritional colitis relate to ulcerative colitis (UC) is uncertain, but studies have suggested that metabolism of the short chain fatty acid butyrate is impaired in UC.i In these studies, in common with many others, it has not been possible to discover if the change was a primary defect or merely a secondary effect of the disease process.The frequency of 'pouchitis' in ulcerative colitis patients who have colectomy and pouch construction contrasts with the apparent rarity of pouchitis in patients who have the same operation for familial polyposis. '°This implies a potential abnormality of the ileal mucosa in ulcerative colitis that is not evident when the ileum and colon are in normal continuity, with the possible exception of 'backwash ileitis'. In view of this it seems appropriate to study mucosal metabolism in ileal as well as colonic mucosa in UC patients and controls in the expectation that any abnormalities that could be detected in the histologically normal ileum of ulcerative colitis patients would be unlikely to be secondary phenomena.A further problem with the interpretation of some previous studies of mucosal metabolism67 has been concern that the procedure used for isolating a pure epithelial cell population from resected bowel specimens may itself have introduced artefacts, and that these artefactual changes might well have been different in the inflamed colitic tissue from those in the histologically normal colon.This paper describes a technique that allows metabolism of nutrients to be assessed in whole epithelial biopsy specimens, and this technique has been used to assess the metabolism of butyrate and glutamine by ileal and colonic biopsy specimens from patients with idiopathic ulcerative colitis and controls.
1. We speculated that corticosteroids might cause beneficial stimulation of mucus synthesis, since this is a known action of carbenoxolone, itself a corticosteroid, and has also been proposed as a possible mechanism for the protective effect of smoking on ulcerative colitis. We have therefore compared the effects of corticosteroids including carbenoxolone, and nicotine on mucin synthesis, assessed by incorporation of N-[3H]acetylglucosamine into mucin by colonic epithelial biopsies in culture. 2. In histologically normal biopsies from the left colon, hydrocortisone and prednisolone caused a very marked concentration-dependent increase in mucin synthesis, with maximal effect (580 and 300% of control values respectively) at 6 mumol/l [P < 0.001, n = 35 biopsies (seven patients)] and 1.5 mumol/l [P < 0.001, n = 35 (seven patients)] respectively. The maximal effect of hydrocortisone was significantly greater than that of prednisolone (P < 0.05). Carbenoxolone, 0.17 mmol/l, also increased mucin synthesis in the left colon by 242% [P < 0.05, n = 15 (three patients)]. In contrast, these corticosteroids caused only a small, non-significant increase in mucin synthesis in the histologically normal right colon; fludrocortisone, 2 and 20 mumol/l, and aldosterone, 0.1-10 mumol/l, had no effect. Nicotine significantly increased mucin synthesis (180-220% of control values) between 62.5 nmol/l and 6.25 mumol/l (P < 0.05 at all concentrations) in both the right and left colon. In biopsies from the relatively uninvolved right colon of patients with ulcerative colitis, corticosteroids and nicotine caused relatively smaller increases in mucin synthesis. 3. The marked stimulation of mucin synthesis by corticosteroids suggests that this may account, at least in part, for their therapeutic effect in ulcerative colitis.
Intraluminal duodenal diverticulum is a recognised but rare cause ofacute pancreatitis. This patient had three attacks of pancreatitis, each requiring a stay in hospital, within a four month period. The apex of the diverticulum was incised endoscopicaily, whereupon peas and food debris gushed from the incision site. The patient has had no further symptoms in the 12 months since the endoscopic procedure. (Gut 1994; 35: 557-559) Intraluminal duodenal diverticulum is thought to be part of the spectrum of congenital abnormalities, which includes duodenal atresia. It usually presents in adults, after enlargement of the diverticulum with food or ingested foreign bodies, resulting in obstruction of the duodenal lumen, or more rarely of the ampulla of Vater. Definitive treatment has historically been surgical, but we report on a patient with recurrent pancreatitis in whom a satisfactory outcome was achieved with an endoscopic sphincterotome. As far as we are aware, this technique has not previously been reported for treatment of an intraluminal diverticulum.graphy showed changes compatible with acute pancreatitis but no other abnormality and plasma calcium and lipid analyses were repeatedly normal. Endoscopic retrograde cholangiopancreatography (ERCP) was scheduled, but before this could be performed, he had a further attack of pancreatitis, which again settled quickly.At ERCP a small (approx 7 mm diameter) diverticular opening was seen at the presumed site of the ampulla of Vater, with a 5 cm long polypoid swelling protruding into the duodenal lumen distal to the ampulla (Fig 1). The mucosa overlying this swelling looked normal, but was baccate (as if containing spherical objects). When prodded with a cannula the texture was soft and compressible. This was initially felt to be a prolapsing ampulla, possibly with a stone at the lower end of a dilated bile duct, although the possibility of an intraluminal diverticulum was considered. The ampullary opening could not be located, and so a small precut was carefully made at the apex of the swelling. On enlarging the opening with a conventional sphincterotome, several peas and other food debris gushed into Gastroenterology Unit
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