An examination of the relationship between the endoscopic appearance of duodenitis and the histological findings in patients with epigastric pain.

The endoscopic appearance of duodenitis is a common finding in patients undergoing endoscopy because of epigastric pain however, the relationship of the visual findings to histology is poorly defined. We set out to ascertain if there was a correlation between the endoscopic and histological appearances of the duodenal mucosa. Consecutive patients with epigastric pain referred for diagnostic gastroduodenoscopy were studied. The visual appearances of 'duodenitis' (erythema, erosions and sub-epithelial haemorrhage) were reported independently by two endoscopists. Duodenal biopsies were taken and assessed for: neutrophil infiltrate, mononuclear infiltrate, gastric metaplasia, villous atrophy and a breach in the mucosa. H pylori status was determined. Of the 93 patients with endoscopic features of duodenitis an increase in histological markers of inflammation was found in 75 (81%). However, histological inflammation was absent or minimal in 68 (73%). Conversely, biopsies from normal-looking mucosa revealed histological evidence of inflammation in 26 (27%). For patients with the endoscopic features of duodenitis the positive & negative predictive value for neutrophilic infiltrate was 39% and 98% respectively. Biopsies from erosions confirmed a breach in the mucosa in only 2 of 40 patients. Neutrophilic infiltrate occurred with NSAI ingestion and infection with H pylori. The endoscopic appearance of the duodenal mucosa is unreliable in determining the presence of histological inflammation. The endoscopic appearance of 'erosions' is not usually associated with a mucosal breach.

Myosin light chain kinase inhibition: correction of increased intestinal epithelial permeability in vitro.

PURPOSE: To examine whether myosin light chain kinase (MLCK) inhibitors can reduce intestinal epithelial permeability increases in vitro. MATERIALS AND METHODS: Isolated rat, mouse and human colonic tissue mucosae and Caco-2 monolayers were exposed to cytochalasin D (cD) and sodium caprate (C10), in the absence and presence of the MLCK inhibitors, ML-9 and D PIK. Transepithelial electrical resistance (TEER) and Papp of [14C]-mannitol or FITC-dextran 4000 (FD-4) were measured. Western blots were used to measure MLC phosphorylation. RESULTS: Increases in Papp of [14C]-mannitol and decreases in TEER were induced by tight junction openers. These changes were attenuated by ML-9. D-PIK offset the FD-4 Papp increase induced by C10 in Caco-2 only, while ML-9 and PIK inhibited MLC directly, cD induced constriction of peri-junctional actin in Caco-2 monolayers, but this was prevented by ML-9. Although mannitol fluxes across colonic mucosae from dextran-sulphate (DSS)-treated mice were higher than control, they were not ameliorated by either ML-9 or PIK in vitro. CONCLUSIONS: ML-9 inhibits paracellular permeability increases in several intestinal epithelial models. D-PIK reduced stimulated paracellular fluxes in Caco-2 monolayers, but not in tissue. Pre-established increases were not modified by two MLCK inhibitors in a mouse model of IBD.

Alteration of sulfate and hydrogen metabolism in the human colon by changing intestinal transit rate.

OBJECTIVES: Changes in intestinal transit rate are also implicated in the etiology of many colonic diseases and strongly influence many metabolic processes in the colon. We set out to investigate whether intestinal transit time could influence the activity of the hydrogen-consuming bacterial flora and sulfate metabolism. METHODS: Normal volunteers underwent four interventions while taking a low-sulfate diet: placebo, sulfate supplements, or sulfate supplements with either senna or loperamide. Stools were cultured and analyzed for sulfate, sulfide, methionine, sulfate reduction rates, methionine reduction rates, acetic acid production rates, methane production rates, short-chain fatty acids, and bile acids. Urine was analyzed for sulfate. RESULTS: The addition of sulfate alone increased fecal and urinary excretion of sulfate, fecal sulfide, sulfate reduction rates, and acetic acid production rates; it reduced fecal methanogenic bacterial concentrations. Faster intestinal transit increased fecal sulfate, sulfide, bile acids, the reduction rates of sulfate, and methionine and the production rates of acetic acid. Reduction in fecal methanogens and methane production was seen. The reverse effects were seen with loperamide. CONCLUSIONS: Both sulfate supplements and changes in intestinal transit rate markedly alter the activity of the colonic bacterial flora with respect to sulfate metabolism and hydrogen disposal. Dietary influences on intestinal transit and sulfate consumption may influence disease processes. While a variety of processes govern sulfate metabolism and hydrogen disposal, our knowledge is far from complete. How far the observed changes in sulfate metabolism seen in certain diseases are relevant to the pathogenesis of the disease or secondary to the disease itself is unclear.