Tag: Chloride secretion

How can we battle the scourge of diarrhea: CONCLUSIONS

Diarrhea remains a worldwide scourge, and its prevalence and impact is also under-recognized and perhaps increasing even in developed countries. Studies from our laboratory, as well as many others, are beginning to reveal the spectrum of mechanisms that are exploited by invasive pathogens, which complements our understanding of enterotoxigenic diarrheal disease. We may also gain…

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Salmonella typhi

How can we battle the scourge of diarrhea: SHOULD WE BATTLE?

I will finally make some points about the potential benefits to the host of a diarrheal response, based in part on some new studies we have initiated with another invasive pathogen, Salmonella typhi. This organism is very closely related to S typhimurium at the genetic level, yet causes a quite different clinical picture . Thus,…

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How can we battle the scourge of diarrhea: INTESTINAL EPITHELIAL CELL FUNCTIONS (Part 4)

We also examined whether probiotic bacteria, commensals that exert health benefits beyond inherent nutrition if ingested in certain numbers, are capable of altering signaling events and their functional outcomes induced in epithelial cells by invasive pathogens. We undertook these studies because there is significant anecdotal evidence that probiotic preparations alleviate the symptoms of intestinal infections…

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Late signaling events

How can we battle the scourge of diarrhea: INTESTINAL EPITHELIAL CELL FUNCTIONS (Part 3)

Infected epithelial cells also show heightened secretory responses to a variety of cAMP-dependent and other chloride secretagogues, such as galanin, further exacerbating fluid loss. The increases in both basal and stimulated secretion appear to result from the sequential induction of expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In turn, the products of…

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How can we battle the scourge of diarrhea: INTESTINAL EPITHELIAL CELL FUNCTIONS (Part 2)

We speculate, therefore, that the recruitment of EGF receptor-dependent signaling events that limit calcium-dependent chloride secretion allows the Salmonella infection to become established by preventing the short burst of chloride (and accompanying fluid) secretion from washing away the bacteria before they are able to invade (Figure 2). While these data do not explain why patients…

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Early signaling events

How can we battle the scourge of diarrhea: INTESTINAL EPITHELIAL CELL FUNCTIONS (Part 1)

Let us now consider the mechanisms of diarrheal disease caused by invasive bacterial pathogens. Invasive bacteria account for more than half of the mortality due to foodborne illness in the United States, yet we are only beginning to understand how they cause diarrhea . This lack of understanding contrasts with that for diarrhea caused by…

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How can we battle the scourge of diarrhea: EPITHELIAL SECRETORY FUNCTION (Part 3)

We are beginning to develop an understanding of the complex set of integrated signalling events that cooperate to limit the extent of epithelial chloride secretion in intestinal epithelial cells, details of which are provided in Figure 1. The significance of these findings lies in the knowledge that chloride secretion is demonstrably subject to inhibitory as…

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Signaling pathways

How can we battle the scourge of diarrhea: EPITHELIAL SECRETORY FUNCTION (Part 2)

Moreover, because EGF receptors and relevant ligands (including EGF itself and transforming growth factor-alpha [TGFa]) may be regulated in the setting of intestinal injury and inflammation, the beneficial effects of EGF on net fluid transport may represent an adaptive response that protects the body from excessive fluid loss . We have shown that EGF inhibits…

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How can we battle the scourge of diarrhea: EPITHELIAL SECRETORY FUNCTION (Part 1)

Thus, in a disease like cholera, where there is an irreversible increase in cAMP levels in intestinal epithelial cells, diarrhea is likely worsened by the simultaneous stimulation of chloride secretion and inhibition of sodium chloride absorption. Notably, however, sodium-coupled nutrient absorption remains intact, providing a rationale for treatment with oral rehydration solutions. We and other…

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basolateral membrane of crypt epithelial cells

How can we battle the scourge of diarrhea: BASIC MECHANISMS OF DIARRHEA (Part 3)

Glucose then exits basolaterally via a facilitated diffusion glucose transport pathway (GLUT-2). In between meals, when nutrients are not available, water absorption can alternatively be driven by the coupled uptake of chloride and sodium across the apical membrane via the downregulated in adenoma (DRA) chloride/bicarbonate exchanger and the sodium/hydrogen exchanger (NHE-3), respectively . Again, this…

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