Colonic epithelium

E. histolytica invades mucosal cells of colonic epithelium, producing the classic flask-shaped ulcer in the submucosa. The trophozoite toxin has a cytocidal effect on cells. If the trophozoite gets into the portal circulation, it will be carried to the liver, where it produces abscess and periportal fibrosis. Liver abscesses are more common in men than women and are rarely seen in children. Amebic ulcerations can affect the perineum and genitalia, and abscesses may occur in the lung and brain. 

Water-soluble methylglyoxal adenine derivative 11 has recently been reported as a potentiator of wild-type and F508del-CFTR mutations in several cell lines [55]. Ex vivo addition of 11 to cftr mice colonic epithelium induced a dose-dependent elevation of chloride secretion with a measured EC50 of 175 + 1.1 pM. In vivo, in cftr+/ mice, addition of 11 in the presence of isoprenaline induced a dose-dependent salivary secretion with an EC50 of 7.1 + 1.1 pM whereas no effect of isoprenaline and 11 was observed on the salivary secretion of cftr mice. 

Roedinger WEW The colonic epithelium in ulcerative colitis An energy deficient disease Lancet 1980 ii 712—715. 

Sequential mutations within colonic epithelium result in cellular replication or enhanced invasiveness. Genetic changes include mutational activation of oncogenes and inactivation of tumor suppressor genes. 

By virtue of rendering iron catalytically inactive, dietary phytate may also suppress the incidence of colonic cancer (J2j>). Intestinal aerobic bacteria and/or minor inflammatory events generate substantial amounts of O27 leading to OH formation and lipid peroxidation. These two processes are thought to be important elements in tissue injury which occurs during inflammation. This argument is compatible with the observation that colonic cancer is frequently preceded, or accompanied, by pigmentation of the colonic epithelium lipofuscin, a byproduct of lipid... 

An increasing number of preclinical and clinical studies have been conducted in recent years aiming to clarify the barrier function of the colonic epithelium in more detail and to devise drug delivery strategies, for example, by modulating factors limiting colonic drug absorption. For preclinical... 

Thus, the apparent membrane permeability characteristics of hydrophilic compounds listed in Table 3.4 indicate that colonic epithelium is different from small intestinal epithelium in selectivity, or size or density distribution of the paracellular pathway. This is further complicated because of the possible involvement of unidentified carriers or channels for some compounds, as suggested for glycerol and D-xylose. However, the colon-to-SI ratios of the apparent membrane permeability are generally comparable with (or lower than) those calculated considering the morphological surface area, suggesting that such factors are not in favor for colonic absorption in most cases. Matching... 

Poquet L, Clifford MN, Williamson G. 2008b. Transport and metabolism of ferulic acid through the colonic epithelium. Drug Metab Dispos 36 190-197. 

A high fat diet may increase excretion of sterol metabolites in the gut, which in turn may promote tumorigenesis in the colonic epithelium. 

Sawada, T. Ogawa, T. Tomita, M. Hayashi, M. Awazu, S. Role of paracellular pathway in non-electrolyte permeations across rat colon epithelium enhanced by sodium caprate and sodium caprylate. Pharm. Res. 1991, 8, 1365-1371. 

The permeability of the colonic epithelium may not be sufficient for achieving a transport rate required for therapeutic activity. This hurdle may be overcome. 

Short-chain fatty acids, especially butyrate, are a preferred source of energy for the colonic epithelium. There is evidence to suggest that butyrate enemas are effective in the treatment of ulcerative cohtis. The seeds of Plantago ovata (a source of fermentable dietary fiber) increase fecal concentrations of butyrate and acetate. In a randomized, open, parallel-group, multicenter study in 105 patients with ulcerative cohtis, P. ovata seeds 10 mg bd were as effective as mesalazine 500 mg tds in maintaining remission over 12 months (10). Adverse effects were similar in the two groups, and included constipation, flatulence, nausea, and diarrhea. 

Riegler M, Sedivy R, Pothoulakis C, etal. (1995) Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. In J. Clin. Invest 95 2004-2011. 

S., Cho, K.R. and Fearon, E.R. (2002) CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology, 123 (5), 1565-1577. 

It is well appreciated that dietary fat retards proximal gastrointestinal transit. Since absorption of fats is generally complete in the healthy gut by the distal ileum, the colon epithelium is not equipped to process fats and excess load leads to steattorhea. 

The bulk luminal pH is heavily affected by the fermentation of carbohydrates to short-chain fatty acids however, near the colonic mucosa, the pH rises and changes in the bulk pH have little effect on the epithelial microclimate. Bicarbonate/chloride exchange is partly responsible for raising the pH against the challenge posed by the high colonic pCOi and the acid production by fermentation. The mucus has been shown to contain a distinct carbonic anhydrase, produced by epithelial tissues that help to carefully regulate the thick unstirred layer of the colonic epithelium. 

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