Intestinal adhesions

Obstruction of the intestines, intestinal adhesions and intussusception are acute abdominal syndromes and they have severe pathological consequences. They cause accumulation of feces, Qi, blood, heat and fire-toxin in the intestines. As well as regular western medical treatment, certain intestinal adhesions, intussusception and the primary stage of simple or partial intestinal obstruction can be treated with Chinese herbal medicine. 

Multilamellar liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) were prepared by the formation of a thin lipid film and subsequent sonication, and coated with chitosan (Ch) [36], Liposomes with a size of approximately 5 pm were used in the experiment. The Ch-coated and plain liposomes were compared in terms of mucoadhesion to the rat stomach and intestinal parts. Although both the liposomes were less adhesive to the stomach, Ch-coated liposomes displayed much higher mucoadhesion to all the intestinal parts in vitro than the plain liposomes. The intestinal adhesion of the plain liposomes were minimal. Further, Ch-coated liposomes showed a great mucoadhesion to the intestine at acidic and neutral pH values. This was also confirmed by fluorescence microscopy when pyrene-loaded Ch-coated liposomes were used in the mucoadhesion test. 

Intestinal adhesion, the most frequent cause of bowel obstruction, cannot be demonstrated on sonography. Likewise, internal hernia and congenital fibrotic band can rarely be identified at sonography. Previous history of abdominal operation in patients without a sonographically visible cause of obstruction can lead to a diagnosis of adhesive ileus. 

A Lactobacillus strain was recently shown to inhibit competitively adhesion of enteropathogenic E. coli to pig ileum and interfered with bacterial attachment to the mucosal layer of ileal conducts (Blomberg et al., 1993). Although L. acidophilus inhibits the adhesion of several enteric pathogens to human intestinal cells in culture, when pathogen attachment preceded L. acidophilus treatment, no inhibitory interference occurred indicating that steric hindrance of site occupation is important in the inhibition of adhesion. Thus, therapeutic use is likely to be limited to preventive application of probiotics. 

More recently, increasing research attention has focused upon the use of mucoadhe-sive delivery systems in which the biopharmaceutical is formulated with/encapsulated in molecules that interact with the intestinal mucosa membranes. The strategy is obviously to retain the drug at the absorbing surface for a prolonged period. Non-specific (charge-based) interactions can be achieved by the use of polyacrylic acid, whereas more biospecihc interactions are achieved by using selected lectins or bacterial adhesion proteins. Despite intensive efforts, however, the successful delivery of biopharmaceuticals via the oral route remains some way off. 

DETA/NO is a stable NO-donor with the longest NO generation half-life of approximately 20 h. Thrombelastography performed on rabbit blood showed that DETA NONOate-derived NO significantly decreased coagulation activity and platelet activation [48]. Monitoring by intravital microscopy showed that DETA/NO attenuated the platelets/endothelial cells adhesion response to endotoxins (e.g. lipopolysaccharides) in murine intestinal venules [49]. The main mechanism of the antiadhesive action of DETA/NO on platelets was activation of soluble guanylate cyclase [49]. 

Baumler, A. J., TsoUs, R. M., Bowe, F. A., Kusters, J. G., Hoffmann, S., and Heffron, F. (1996a). The pef flmbrial operon of Salmonella typhimurium mediates adhesion to murine small intestine and is necessary for fluid accumulation in the infant mouse. Infect. Immun. 64, 61-68. 

Cleary, J., Lai, L.-C., Shaw, R. K., Straatman-lwanowska, A., Donnenberg, M. S., Frankel, G., and Knutton, S. (2004). Enteropathogenic Escherichia coli (EPEC) adhesion to intestinal epithelial cells Role of bundle-forming pili (BFP), EspA filaments, and intimin. Microbiology 150, 527-538. 

Laux, D. C., McSweegan, E. F., and Cohen, P. S. (1984). Adhesion of enterotoxigenic Escherichia coli to immobilized intestinal mucosal preparations A model of adhesion to mucosal surface components. /. Microbiol. Methods 2, 27-39. 

Smith, C. J., Kaper, J. B., and Mack, D. R. (1995). Intestinal mucin inhibits adhesion of human enteropathogenic Escherichia coli to HEp-2 cells. J. Pediatr. Gastroenterol. Nutr. 21,269-276. 

Shigella Colonization and invasion of epithelial cells in large intestine Replication in cytoplasm Aeromonas sp. Endotoxins, exotoxins, invasins, extracellular enzymes, adhesions, siderophores Clostridium Neurotoxins botulinum... 

A pulsed system, called Time-Clock System, has been developed. It comprises a solid dosage form coated with a hydrophobie surfactant layer to which a water-soluble polymer is attached to improve adhesion to the core [66]. The thickness of the outer layer determines the time required to disperse in an aqueous environment. Following the dispersion of the outer layer, the eore becomes available for dispersion. An advantage is that eommon pharmaceutical excipients can be used to manufacture this system. Studies performed on human volunteers showed that the lag time was not affeeted by gastrie residence time. Furthermore, the dispersion of the hydrophobic film was not influenced by the presence of intestinal digestive enzymes or by the mechanieal aetion of the stomach. 

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