Inflammatory intestinal response

Kirkpatrick BD, Daniels MM, Jean SS, Pape JW, Karp C, Littenberg B, Fitzgerald DW, Led-erman HM, Nataro JP, Sears CL Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian children. J Infect Dis 2002 186 94-101. 

Two case studies of acute intrusion of barium sulfate into the peritoneal space during barium enema examination of four men showed barium sulfate caused an acute inflammatory tissue response (Kay 1954 Yamamura et al. 1985), and in one case resulted in formation of a fibrous granuloma (Kay 1954). This is an extremely rare mode of entry and not of significant concern for individuals exposed at a hazardous waste site. Increased fluid accumulation in the intestinal lumen of rats was observed after intraperitoneal injection of barium chloride (Hardcastle et al. 1983b, 1985) however, this observation is not significant for individuals exposed at hazardous waste sites because of the route of exposure and because there has been no documentation of this effect occurring in humans following normal exposure routes. 

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

An alteration in the inflammatory response regulated by intestinal epithelial cells may also contribute to development of IBD. This may involve inappropriate processing of antigens presented to the GI epithelial cells.3 The inflammatory response in IBD may actually be directed at bacteria that normally colonize... 

Antibiotics have been studied based on the rationale that they may interrupt the inflammatory response directed against endogenous bacterial flora. Metronidazole and ciprofloxacin have been the two most widely-studied agents.32 Metronidazole may benefit some patients with pouchitis (inflammation of surgically-created intestinal pouches) and patients with CD who have had ileal resection or have perianal fistulas. Ciprofloxacin has shown some efficacy in refractory active CD. Both drugs may cause diarrhea, and long-term use of metronidazole is associated with the development of peripheral neuropathy. 

Behnke, J.M., Rose, R. and Little, J. (1994b) Resistance of the hookworms Ancylostoma ceylanicum and Necator americanus to intestinal inflammatory responses induced by heterologous infection. Intemationaljoumal of Parasitology 24, 91-101. 

The leading hypothesis for the development of chronic intestinal inflammation is that an abnormal immune response to normal flora might be crucial. This loss of tolerance might be due to a lack of regulatory mediators or cells, or a breakdown in barrier function which makes possible the access of inflammatory bacterial products to the local immune system, thereby overwhelming the normal regulation [3], These possibilities were supported by... 

Histamine (B). Histamine is stored in basophils and tissue mast cells. It plays a role in inflammatory and allergic reactions (p. 72, 326) and produces bronchoconstriction, increased intestinal peristalsis, and dilation and increased permeability of small blood vessels. In the gastric mucosa, it is released from enterochromaffin-like cells and stimulates acid secretion by the parietal cells. In the CNS, it acts as a neuromodulator. Two receptor subtypes (G-pro-tein-coupled), H and H2. are of therapeutic importance both mediate vascular responses. Prejunctional H3 receptors exist in brain and the periphery. 

Sulfasalazine is absorbed in the proximal intestine and is then excreted unchanged in the bile. In consequence most of orally administred sulfasalzine reaches the colon as such. It is then split by the intestinal flora into its components sulfapyridine, a sulfonamide antimicrobial agent, and 5-aminosalicylic acid (5-ASA). It has been proven that in inflammatory bowel disease 5-ASA is responsible for the beneficial effects while the sulpha component only contributes to the adverse reaction profile. Although some 5-ASA is absorbed and excreted in urine with a half-life of 0.5-1.5 hours, most is eliminated unchanged in the faeces. Sulfapyridine is to a major extend reabsorbed, metabolized in the liver and excreted in the urine with a half-life, depending on the acetylator phenotype, between 5 and 15 hours. 

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