Distal colon

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

Pseudomembranous colitis Same symptoms as colitis, but sigmoidoscopic examination reveals a characteristic membrane with adherent yellow or off-white plaques, usually in distal colon. 

B Hoffmann, I Nagel, W Clauss. (1990). Aldosterone regulates paracellular pathway resistance in rabbit distal colon. J Comp Physiol B 160 381-388. 

The results showed there to be an asymmetry in colonic distribution among healthy subjects, with two-thirds of the administered dose in the proximal colon and one-third in the distal colon. In the patients, this difference was even more pronounced, with only one-tenth of the administered dose in the distal segment. 

Fig. 23.4. Distribution of resin labeled with 111 In after four successive daily (morning) administrations among a cohort of normal volunteers and patients with active colitis. AC, ascending colon DC, distal colon RS, rectosigmoid colon TC, transverse colon.

Hammer, J., Pruckmayer, M., Bergmann, H., Rletter, K., Gangl, A., The distal colon provides reserve storage capacity during colonic fluid overload, Gut, 1997, 41, 658—663. 

Hebden, J. M., Blackshaw, E., Perkins, A. C., Wilson, C. G., Spiller, R. C., Limited exposure of the healthy distal colon to orally dosed... 

Spencer NJ, Smith TK Simultaneous intracellular recordings from longitudinal and circular muscle during the peristaltic reflex in guinea-pig distal colon. J Physiol 2001 533 ... 

Steinmetz and others (1994) have shown that risk of cancer in the distal colon was 50% lower in women with the highest consumption of garlic than in women who did not consume garlic. 

Lopez-Oliva ME, Agis-Torres A, Garcia-Palencia P, Goni I and Munoz-Martinez E. 2006. Induction of epithelial hypoplasia in cecal and distal colonic mucosa by grape antioxidant dietary fiber. Nutr Res... 

Additionally, tegaserod at low nanomolar concentrations increases intracellular cAMP concentrations in crypt cells isolated from rat distal colon and stimulates chloride and water secretion by activation of 5-HT4 receptors [34,35], These findings suggest a modulatory effect on intestinal electrolyte and water secretion in vivo. 

The anatomy of the distal colon, with its thick muscular walls, suggests a predominantly propulsive activity. Studies with single administrations of pellets or Pulsincap devices suggested that the distal part of the transverse colon area is difficult to treat since this area and the descending colon function as a conduit. Steady-state measurements confirm this assertion (48) and Weitschies group have also reported data showing mass movements propel objects quickly through the distal transverse colon. 

Morita, T., Kasaoka, S., Hase, K., and Kiriyama, S. (1999). Psyllium shifts the fermentation site of high-amylose cornstarch toward the distal colon and increases fecal butyrate concentration in rats. J. Nutr. 129,2081-2087. 

Luciano, L., Real, E., Rechkemmer, G., and von Engelhard , W., Structure of the zonula occludentes and the permeability of the epithelium to short-chain fatty acids in the proximal and the distal colon of guinea pig, J. Membr. Biol., 82 145-156 (1984). 

Given the large number of variables, Thomas et argued that it was important to carry out both univariate and multi-variate analyses of the data. Both types of analysis showed that LBTT, the activity of the 7a-dehydroxy-lation, and the distal colonic luminal pH were all significant risk factors for high proportions of DCA in serum (and by implication, in bile). Based on these results, the authors concluded that there was indeed prolonged colonic transit in conventional gallstone patients and that this, in turn, was likely to result in increased DCA formation, solubilisation (and therefore bioavailability) and absorption. 

The fact that the luminal pH of the healthy distal colon is slightly higher than that of the proximal small intestine has led to the development of oral dosage forms that are intended to release the drug at the colonic pH (pH-controlled drug release). 

Colonic motor function also has cyclic slow waves in the proximal colon. These contractions are primarily retrograde in the proximal colon, allowing segmentation and liquid reabsorption. In the distal colon a propulsive mass movement occurs intermittently. This may be stimulated by food ingestion and is termed the gastrocolonic reflex. 

To avoid the side effects of sulfapyridine, various preparations to target 5-ASA directly to sites of disease have been formulated. Also known as mesalamine, 5-ASA has been formulated in oral forms (Pentasa, Asacoi). Pentasa is a time-release capsule that releases the drug throughout the GI tract. Asacoi is a pH-dependent-release preparation that delivers drug to the distal small bowel and colon. The response of ulcerative colitis to this formulation appears to be identical to that seen with sulfasalazine. Mesalamine can also be administered as a suppository (Canasa) or enema (Rowasa) for distal colonic disease. 

Systemic administration of colonic carcinogois yields the entire spectrum of changes seen in human colon cancer, including abnormal crypt architecture with disrupted proliferation, papillary and adenomatous polyps, carcinoma in situ, and adenocarcinoma (Thumherr et al., 1973). The distal colon is affected with the greatest frequency, and squamous cell canc of the anus is also produced. Dietary fat enhances the production of colonic tumors (Nigro et al., 1975), perhaps by increasing bile flow (Narisawa et al., 1974). 

The effectiveness of 5-ASA therapy depends in part on achieving high drug concentration at the site of active disease. Thus, 5-ASA suppositories or enemas are useful in patients with ulcerative colitis or Crohn s disease confined to the rectum (proctitis) or distal colon (proctosigmoiditis). In patients with ulcerative colitis or Crohn s colitis that extends to the proximal colon, both the azo compounds and mesalamine formulations are useful. For the treatment of Crohn s disease involving the small bowel, mesalamine compounds, which release 5-ASA in the small intestine, have a theoretic advantage over the azo compounds. 

Deschner, E.E. (1978) Early proliferative defects induced by six weekly injections of 1,2-dimethylhydrazine in epithelial cells of mouse distal colon. Z. Krebsforsch., 91, 205-216 Deschner, E.E. Long, EC. (1977) Colonic neoplasms in mice produced with six injections of... 

---