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Intestinal mucosa layers

V. cholerae is a gram-negative bacillus. Vibrios pass through the stomach to colonize the upper small intestine. Vibrios have filamentous protein extensions that attach to receptors on the intestinal mucosa, and their motility assists with penetration of the mucus layer.2 The cholera enterotoxin consists of two subunits, one of which (subunit A) is transported into the cells and causes an increase in cyclic AMP, which leads to a deluge of fluid into the small intestine.20 This large volume of fluid results in the watery diarrhea that is characteristic of cholera. The stools are an electrolyte-rich isotonic fluid, the loss of which results in blood volume depletion followed by low blood pressure and shock.2 Of note, the diarrheal fluid is highly infectious. [Pg.1122]

The identification and characterization of cell culture systems (e.g., Caco-2-cells) that mimic in vivo biological barriers (e.g., intestinal mucosa) have afforded pharmaceutical scientists the opportunity to rapidly and efficiently assess the permeability of drugs through these barriers in vitro. The results generated from these types of in vitro studies are generally expressed as effective permeability coefficients (Pe). If Pe is properly corrected to account for the barrier effects of the filter (PF) and the aqueous boundary layer (PAbl) as previously described in Section II.C, the results provide the permeability coefficient for the cell monolayer... [Pg.325]

Figure 8.1 (A) Cross-sectional view of the organization of the small intestine, illustrating the serosa, the longitudinal and circular muscle layers (=muscularis externa), the submucosa, and the intestinal mucosa. The intestinal mucosa consists of four layers, the inner surface cell monolayer of enterocytes, the basal membrane, the lamina propria (connective tissue, blood capillaries), and the muscularis mucosae, (B) Schematic representation of an enterocyte (small intestinal epithehal cell) (according to Tso and Crissinger [151], with permission). Figure 8.1 (A) Cross-sectional view of the organization of the small intestine, illustrating the serosa, the longitudinal and circular muscle layers (=muscularis externa), the submucosa, and the intestinal mucosa. The intestinal mucosa consists of four layers, the inner surface cell monolayer of enterocytes, the basal membrane, the lamina propria (connective tissue, blood capillaries), and the muscularis mucosae, (B) Schematic representation of an enterocyte (small intestinal epithehal cell) (according to Tso and Crissinger [151], with permission).
Bile contains conjugates of cholic acid and cheno-deoxycholic acid, which emulsify dietary fat, facilitate lipolysis, and transport lipid molecules through the unstirred layer of the intestinal mucosa by micellar solubilization. The ability of bile salts to promote lipid... [Pg.31]

The epithelium is supported underneath by lamina propria and a layer of smooth muscle called muscularis mucosa (3-10 cells thick). These three layers, i.e., the epithelium, lamina propria, and muscularis mucosa, together constitute the intestinal mucosa.On the apical surface, the epithelium along with lamina propria projects to form villi. The cell membranes of epithelial cells that comprise the villi contain uniform microvilli, which give the cells a fuzzy border, collectively called a brush border. These structures, although greatly increase the absorptive surface area of the small intestine, provide an additional enzymatic barrier since the intestinal digestive enzymes are contained in the brush border. In addition, on the top of the epithelial layer lies another layer, the UWL, as previously described. The metabolic and biochemical components of the epithelial barrier will be discussed. [Pg.1246]

Fig. 2 Schematic depiction of two-section villi and a crypt to illustrate the small intestine mucosa. Also shown is an aqueous boundary layer located at the intestinal lumen and membrane interface. (Illustration by Leigh A. Rondano, Boehringer Ingelheim Pharmaceuticals, Inc.)... Fig. 2 Schematic depiction of two-section villi and a crypt to illustrate the small intestine mucosa. Also shown is an aqueous boundary layer located at the intestinal lumen and membrane interface. (Illustration by Leigh A. Rondano, Boehringer Ingelheim Pharmaceuticals, Inc.)...
With the difficulties associated with accurate estimation of permeability based only on physicochemical properties, a variety of methods of measuring permeability have been developed and used, among which are (l)cul-tured monolayer cell systems, such as Caco-2 or MDCK ( 2 diffusion cell systems that use small sections of intestinal mucosa between two chambers (3) in situ intestinal perfusion experiments performed in anesthetized animals such as rats and (4)intestinal perfusion studies performed in humans (40,54-62). All of these methods offer opportunities to study transport of drug across biological membranes under well-controlledconditions. Caco-2 mono-layer systems in particular have become increasingly commonly used in recent years and human intestinal perfusion methods are also becoming more commonly available. Correlations between Caco-2 permeability and absorption in humans have been developed in several laboratories (63-72). As shown in Fig. [Pg.659]

Figure 11.26 A schematic diagram of an apparatus used to obtain estimates of the passive permeability of a drug candidate across the intestinal mucosa using Caco-2 cells. A monolayer of Caco-2 cells is grown on a porous polyethylene terephthalate (PET) membrane (a so-called confluent monolayer of cells that grows only in two dimensions on such a substrate from an initial small inoculation). In the experiment the cells are submerged in Hanks s Balanced Salt Solution (HBSS) buffer (contains Na+, K+, CP, phosphate, glucose, and in some formulations also Ca +, Mg + and S04 ) the Caco-2 cell layer provides the only connection between an apical (donor) reservoir, into which the drug candidate is dosed, and a basolateral (receiver) reservoir. For the assay, aliquots are removed for analysis from the apical reservoir at Omin, and from both reservoirs at 120 min. Reproduced from Van Pelt, Rapid Commun. Mass Spectrom. 17, 1573 (2003), with permission of John Wiley Sons Ltd. Figure 11.26 A schematic diagram of an apparatus used to obtain estimates of the passive permeability of a drug candidate across the intestinal mucosa using Caco-2 cells. A monolayer of Caco-2 cells is grown on a porous polyethylene terephthalate (PET) membrane (a so-called confluent monolayer of cells that grows only in two dimensions on such a substrate from an initial small inoculation). In the experiment the cells are submerged in Hanks s Balanced Salt Solution (HBSS) buffer (contains Na+, K+, CP, phosphate, glucose, and in some formulations also Ca +, Mg + and S04 ) the Caco-2 cell layer provides the only connection between an apical (donor) reservoir, into which the drug candidate is dosed, and a basolateral (receiver) reservoir. For the assay, aliquots are removed for analysis from the apical reservoir at Omin, and from both reservoirs at 120 min. Reproduced from Van Pelt, Rapid Commun. Mass Spectrom. 17, 1573 (2003), with permission of John Wiley Sons Ltd.
The presence of a layer of thick surface mucus, covering intestinal mucosa, has been postulated to constitute a mechanical barrier, preventing normal BA absorption absorption of BA to the abnormal intestinal mucus may occur, as it has been demonstrated to occur in vitro[19]. The addition of N-Acety1-Cysteine to pancreatic enzymes resulted in an improvement of fat absorption in CF patients with steatorrhea[20], but this finding must be confirmed by clinical studies on larger patients population. [Pg.238]

Such interactions are directly relevant to the effect of surfactants on drug absorption. Fig. 10.5a shows the relationship between absorption of salicylate or L-valine across rat jejunal tissue in vivo and release of protein and phospholipid by a series of surfactants. Fig. 10.5b shows the relative activity of a series of non-ionic surfactants of the Brij series and sodium taurodeoxycholic acid (NaTDC), sodium dodecyl sulphate (NaDS) and CTAB [30]. An association between protein release and increased absorption of solutes has also been reported by Feldman and Reinhard [31] and Walters et al. [32]. Anionic, non-ionic and cationic surfactants tended to accelerate the breakdown of the mucous layer covering the epithelium and at high concentrations were thought to interfere with the structure of the mucosal surface itself. Exposure of various anionic and nonionic surfactants to rabbit intestinal mucosa causes epithelial desquamation and necrosis [33]. [Pg.622]


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See also in sourсe #XX -- [ Pg.184 ]




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