Epithelia colon

Differences have been observed in the infrared spectra of normal and abnormal tissues for cervical epithelium, - colon, prostrate gland, etc. In the region 1100-950 cm (9.09-10.53 pm), a loss of structure and a slight increase in intensity has been observed between normal and cancerous cells. 

Whipworm (Trichuris trichiurd) adult females are 5 cm long. These worms thread their entire body into the epithelium of the colon, where they feed on tissue juice and small amounts of blood. Infections of several hundred worms may cause irritation and inflammation of the mucosa, with abdominal pain, diarrhea, and gas. Eggs are discharged and passed into the feces. Infections result from the swallowing of eggs that are obtained directly from contaminated soil. Untreated adult worms Hve for years. 

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... 

Helicobacter pylori normally resides in the human stomach and is transmitted via the fecal-oral route or through ingestion of fecal-contaminated water or food. Infection with HP is more common in developing countries because of crowded conditions and the presence of contaminated food and water. HP colonization does not necessarily reflect an active infection since the organism can attach itself to the gastric epithelium... 

The passage of fluids into and out of the colon is regulated by epithelial cells. In IBS, the colonic lining (epithelium) appears to work properly. However, increased movement of the contents in the colon can overwhelm its absorptive capacity. 

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. 

Four major tissue layers, from the lumen outward, form the large intestine the mucosa, submucosa, muscularis externa, and serosa (Fig. 88-2). Complete replacement of surface epithelial cells occurs approximately weekly, with the total number of epithelial cells remaining constant in normal colonic tissue. As patients age, abnormal cells accumulate on the surface epithelium and protrude into the stream of fecal matter their contact with fecal mutagens can lead to further cell mutations and eventual adenoma formation.4... 

Familial adenomatous polyposis An inherited condition in which numerous polyps form, mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs 100% of the time when not treated. 

The Caco-2 cell line was isolated from a human colon carcinoma, and has been characterized as one of the best in vitro models of intestinal epithelium. Indeed, in contrast to other intestinal cell lines, Caco-2 cells are able to constitute a homogenous monolayer and to spontaneously differentiate into polarized cells, highly similar to human mature enterocytes, after approximately 2 weeks of culture. Furthermore, the Caco-2 cells present microvillosities at the apical side and have a high transmembrane resistivity, which confirms the fact that the cells are confluent and link to one another via gap junctions. Finally, they can absorb different compounds, express many enzymes involved in intestinal metabolic pathways (Pinto et al. 1983, Musto et al. 1995, Salvini et al. 2002), and give reproducible in vitro results consistent with results obtained in in vivo studies (Artursson and Karlsson 1991). 

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. 

Fig. 1. Typical presentation of pseudomembranous colitis. At endoscopy (left), the mucosal surface of the colon appears hyper-emic and almost completely covered by a yellow-green exudate. The mucosa itself is somewhat eroded. Microscopically (right), the pseudomembrane is composed of inflammatory cells, necrotic epithelium, and mucus in which the overgrowth of microorganisms usually takes place. 

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... 

Recently, an approach mimicking the GI tract and feasible for pharmaceutical dissolution studies has been published [47], Coming from the area of nutritional research, this approach reflects some promising aspects, such as relevant luminal pH values, peristalsis, luminal bacterial colonization, and relevant fluid volumes. However, permeation is only reflected by diffusion through hollow fiber membranes and thus is not in the scope of this chapter. Nevertheless, it will be interesting to see whether it will be possible to expand such a perfect in vitro device toward a more realistic intestinal epithelium. 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

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). 

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