Search PubMed⌕ Search

Biomedical subjects

S B Formal

Publications and source records attributed to S B Formal.

At least 91 records · Page 5Linked to original sources
PubMed1977

Effect of indomethacin on intestinal water transport in salmonella-infected rhesus monkeys.

Indomethacin, a nonsteroidal anti-inflammatory agent, will abolish salmonella-induced rabbit ileal secretion when given prior to the establishment of infection. In the present study, we assessed whether indomethacin can inhibit salmonella-induced intestinal secretion when administered after infection and net intestinal secretion are well established. A physiological model of salmonellosis, salmonella-infected rhesus monkeys, was used. This model also permitted an examination of the effects of indomethacin in both the small and large intestines. The effect of indomethacin in control monkeys was also studied. Indomethacin caused a striking enhancement of net intestinal water transport in the jejunum,, ileum, and colon of salmonella-infected monkeys. These effects occurred promptly and were of sufficient magnitude in the ileum and colon to cause a reversal in the direction of net transport from net secretion to net absorption. Indomethacin also enhanced net water transport in the jejunum ileum, and colon of normal animals. These data show that indomethacin markedly enhances net intestinal water transport in both the small and large intestines of salmonella-infected monkeys, even when administered after salmonella infection and intestinal secretion are well established. Similar enhancement also occurs in the normal intestine. The mechanism(s) by which indomethacin produces these effects is not known.

Animals↗
PubMed1976

Studies on the pathogenesis of enteric infections caused by invasive bacteria.

Salmonellae, shigellae and some Escherichia coli must invade the intestinal epithelial cell and multiply within the mucosa to cause disease. Although the bacterial cell most likely possesses several properties essential to this invasive ability, the nature of the cell envelope complex is at present the only characteristic which has been implicated in this process. While a number of pathophysiological events result from invasion, some of our recent efforts have concerned the site and mechanism of intestinal fluid loss in salmonellosis and shigellosis. In both these disorders, bacterial invasion of the colonic mucosa, associated with an acute inflammatory reaction and mucosal damage, is regularly seen and colonic salt and water transport is abnormal. These defects may account for mild diarrhoea in salmonellosis and the dysenteric stools of shigellosis. However, in salmonella-infected animals with severe watery diarrhoea and in shigella-infected animals with diarrhoea alone or in combination with dysentery, the jejunum is in a net secretory state. This secretion occurs in the absence of bacterial invasion or morphological abnormalities. Thus, the diarrhoea caused by invasive bacteria may result from the inability of the colon to reabsorb the increased volume of fluid entering it from the small intestine. Although colonic mucosal damage is a feature of invasive-type diarrhoeas, the permeability of both the colon and small intestine to small molecules, mannitol and erythritol, is not altered. Thus intestinal fluid loss cannot be ascribed to transudation. In addition, the results of our Ussing chamber experiments, employing salmonella-infected rabbit ileum, reveal that salt and water secretion is an active process. Since secretion occurs in the jejunum in the absence of bacterial invasion, this might suggest the participation of an enterotoxin. Shigella dysenteriae I is the best-studied invasive organism in which an enterotoxin has been found, yet mutant strains which do not invade but retain the ability to elaborate enterotoxin fail to cause disease in either monkeys or man. Thus, the physiological relevance of Shiga enterotoxin and the mechanism of jejunal secretion in these disorders remain unclear. Recent data suggest that invasive enteropathogens, like the enterotoxin-producing bacteria, activate the mucosal adenylate cyclase-cyclic AMP system and that this activation may play a role in intestinal fluid secretion.

Animals↗
PubMed1976

Role of plasma filtration in the intestinal fluid secretion mediated by infection with Salmonella typhimurium.

The mechanisms whereby invasive enteropathogens, e.g., Salmonella typhimurium, induce intestinal secretion are largely unknown. Since these organisms penetrate the intestinal epithelium, disrupt the brush border, and evoke an acute inflammatory reaction, increased plasma filtration through a damaged, more permeable epithelium might contribute to the secretory process. To examine this possibility, the plasma-to-lumen clearance of two different sized molecules, [51Cr]albumin and [14C]mannitol, was measured in the in vivo rabbit ileal loop and in vivo rhesus monkey models of salmonellosis. In the rabbit ileal loop model, the clearance of neither molecule was increased when compared to cholera toxin-exposed loops. In the rhesus monkey, clearance of [14C]mannitol into the jejunum, ileum, and colon of Salmonella-infected animals did not differ from the observed in control animals. These data indicate that invasion of the intestinal mucosa by S. typhimurium has not substantially altered the permeability characteristics of the intestinal mucosa and that plasma filtration through a damaged, more permeable mucosa does not contribute to the Salmonella-induced intestinal secretory process.

Animals↗
PubMed1976

Fluid and electrolyte transport in rhesus monkeys challenged intracecally with Shigella flexneri 2a.

Shigella flexneri 2a is an invasive enteric pathogen that may produce diarrhea when ingested by human beings and subhuman primates. We have previously shown that shigella diarrhea correlates with water and electrolyte transport abnormalities in the jejunum and colon. Dysentery alone is associated only with colonic transport abnormalities. To define the relationship between invasion and inflammation of the colon and the occurrence of jejunal transport abnormalities, we studied water and electrolyte transport, histology, and bacteriology in rhesus monkeys that were infected by introducing S. flexneri 2a directly into the cecum. In contrast to the pattern of disease seen after oral administration, cecal inoculation resulted in clinical disease in 64% of animals, of which 94% manifested dysentery alone, rarely preceded by mild diarrhea. Histologically, invasion and inflammation was limited to the colon. Secretion of water and sodium occurred in the colon of infected monkeys when compared with controls, whereas transport was normal in the jejunum and ileum. These data further demonstrate that severe dysentery can result from cecal injection of shigellae, but also suggest that the occurrence of watery diarrhea requires and may result from an undefined interaction between the jejunal mucosa and the organisms during transit through the small intestine.

Animals↗
PubMed1976

Activation of intestinal mucosal adenylate cyclase by Shigella dysenteriae I enterotoxin.

Because the mechanism whereby Shigella dysenteriae I enterotoxin induces intestinal secretion is unclear, the effect of this toxin on adenylate cyclase activity in rabbit ileal mucosa was studied under various in vitro and in vivo conditions. Activation of adenylate cyclase by Shigella enterotoxin was observed only when substrate (ATP) concentrations above the Km of adenylate cyclase were employed. These concentrations of ATP are greater than those required to demonstrate activation of adenylate cyclase by cholera toxin. Under optimal assay conditions, doses of Shigella toxin between 5.4 and 900 mug of toxin protein and in vivo incubation times between 6 and 18 hr all increased adenylate cyclase activity by about 100%. Shigella toxin produced significant but highly variable increases in mucosal cyclic AMP concentrations, which were less that the rises seen with a comparable dose of cholera toxin. This variability in cyclic AMP response to Shigella toxin and the disparity between Shigella and cholera toxins' effects on mucosal cyclic AMP are probably the result of the different kinetics of adenylate cyclase activated by these enterotoxins. Mucosal Na-K-ATPase activity was unaffected by Shigella toxin. These observations suggest that alterations in fluid and electrolyte transport induced by Shigella enterotoxin may, in part, be mediated by the adenylate cyclase-cyclic AMP system.

Adenosine Triphosphatases↗
PubMed1976

The role of altered intestinal permeability in the pathogenesis of salmonella diarrhea in the rhesus monkey.

The pathogenesis of Salmonella diarrhea is unclear. Bacterial invasion of the ileal and colonic mucosa resulting in an intense ileocolitis regularly occurs in concert with secretion of water and sodium in jejunum, ileum, and colon. To examine the role of altered permeability in Salmonella diarrhea we studied intestinal histology, water and electrolyte transport, clearance of intravenously injected [14C]erythritol and [3H]mannitol, and changes in transmural electrical potential difference in normal and Salmonella-infected rhesus monkeys. In normal animals, absorption of water and sodium occurred in jejunum, ileum, and colon and a gradient of diminishing permeability from jejunum to ileum to colon for both erythritol and mannitol was observed. Permeability as measured by determining permeability coefficients was not increased by Salmonella infection and in fact was significantly reduced for erythritol in the jejunum of infected animals. Perfusion with hypertonic erythritol and mannitol produced the same streaming potentials (deltaPD) in control and infected animals, indicating no differences in transmucosal permeability. As a positive control, perfusion with 25 mM ethylenediaminetetraacetic acid in normal animals increased permeability, resulting in increased plasma-to-lumen isotope flux and no deltaPD in response to hypertonic perfusates. These data show that despite severe alterations in intestinal histology, transmucosal permeability remains unchanged and thus is not a contributing factor in Salmonella diarrhea.

Animals↗
PubMed1975

Phage conversion of Shigella flexneri group antigens.

A temperate phage, designated Sf6, has been isolated from Shigella flexneri 3a. Characterization of Sf6 revealed that it possesses the capacity for converting the S. flexneri 3,4 group antigen complex to group factor 6. Serological studies and chemical analysis of lipopolysaccharide from converted strains suggest that group factor 6 is a reflection of an acetylation of the preexisting 3,4 antigen complex. Evidence is provided that the 3,4 group antigen complex functions, at least in part, as a cell surface receptor site for Sf6 adsorption.

Absorption↗
PubMed1975

Pathophysiology of Shigella diarrhea in the rhesus monkey: intestinal transport, morphological, and bacteriological studies.

In contrast to the "toxigenic diarrheas" caused by Vibrio cholerae and Escherichia coli, the site and mechanism of fluid loss in shigellosis are unknown. The occurrence of watery diarrhea in shigellosis suggests involvement of the small bowel. Therefore, jejunal, ileal, and colonic water and electrolyte transport was studied in Shigella flexneri 2a-infected monkeys. Infected animals fell into three groups: dysentery alone, diarrhea alone, or diarrhea and dysentery. In controls, net water, sodium, and chloride absorption was seen in the jejunum, ileum, and colon. All infected animals demonstrated diminished colonic absorption or net colonic secretion. In monkeys with dysentery alone, this was the only transport defect observed. In contrast, animals with diarrhea either alone or in combination with dysentery, exhibited net jejunum secretion. Ileal transport was normal in all animals. A severe colitis with intramucosal shigellae was seen in all symptomatic animals. In the jejunum or ileum, however, morphological changes were minimal and bacterial invasion was not seen. Therefore, unlike the "toxigenic" diarrheas," shigellosis is both a small and large intestinal disease. Mucosal invasion of the colon is essential to the development of a morphological and transport defect. Dysentery results from a colonic transport defect, while diarrhea is secondary to jejunal secretion superimposed on the defect in colonic absorption.

Animals↗
PubMed1975

Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin.

Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.

Adenosine Triphosphatases↗