A study of the relationship among survival, gut-origin sepsis, and bacterial translocation in a model of systemic inflammation.

Several factors, including uncontrolled inflammation, gut barrier failure, and sepsis, have been implicated in the development of multiple organ failure. To investigate the relative importance and interrelationships among some of these factors, increasing doses of the inflammatory agent zymosan were used to induce a systemic inflammatory state in mice. At nonlethal doses (0.1 and 0.5 mg/g body weight), zymosan caused injury to the intestinal mucosa, increased intestinal xanthine oxidase activity, and promoted bacterial translocation in a dose-dependent fashion. Inhibition or inactivation of xanthine oxidase activity was effective in reducing mucosal injury and bacterial translocation when zymosan was injected at 0.1 mg/g but not at 0.5 mg/g body weight. At a dose of 1 mg/g, the lethal effects of zymosan appeared to be related to gut-origin sepsis, since cefoxitin (1 mg/g) reduced the seven-day mortality rate from 100% to 20% (p less than 0.01). However, at a zymosan dose of 2 mg/g, antibiotics did not improve survival. Zymosan thus induced gut barrier failure and systemic infection in a dose-dependent fashion. Additionally, the mechanism of zymosan-induced bacterial translocation and the relationship of gut-origin sepsis to survival appeared to be related to the magnitude of the inflammatory insult (the dose of zymosan).

Rat small intestinal mucins: a quantitative analysis.

Although much is known about the qualitative distribution of mucin-secreting goblet cells in the small intestine, the quantitative distribution of stored mucins remains undefined. The purpose of this study was to determine the distribution of neutral stored mucin in the rat small intestine by using morphometric techniques and once established, to verify that this methodology could detect secretion in animals exposed to a known mucin secretagogue. Twelve male Wistar rats (five baseline, five pilocarpine-treated, and two vehicle controls) were fixed by vascular perfusion. After a brief fixation the intestine was removed, cut into 10 equal segments, sliced, and fixed overnight. Methacrylate sections from each segment were stained with periodic acid-Schiff and toluidine blue. For morphometry, the volume of epithelium per surface area of epithelial basal lamina was calculated with a Merz grid. The volume density of stored mucin per epithelium was determined by point-counting on a square lattice grid. Volumes were related to either surface area of epithelial basal lamina or mucosal surface area. Due mostly to contributions by villus stored mucin, the total amount of product was found to increase proximally to distally in the small bowel, with the most dramatic increases occurring in the first three segments. When subjected to pilocarpine, a massive secretory response was evoked, resulting in a near total depletion of crypt stored mucin at all levels of the small bowel. Secretion of villus stored mucin also occurred throughout the small intestine, however reaching levels of significance at only a few points. This study describes the distribution of stored mucin in the small intestine under baseline and accelerated secretory conditions.