Studies from University of Alberta provide new data on gene therapy
2007 NOV 22 -- "A breakdown in intestinal barrier function and increased bacterial translocation are key events in the pathogenesis of sepsis and liver disease. Altering gut microflora with noninvasive and immunomodulatory probiotic organisms has been proposed as an adjunctive therapy to reduce the level of bacterial translocation and prevent the onset of sepsis," scientists in Edmonton, Canada report. "The purpose of this study was to determine the efficacy of a probiotic compound in attenuating hepatic and intestinal injury in a mouse model of sepsis. Wild-type and interleukin-10 (IL-10) gene-deficient 129 Sv/Ev mice were fed the probiotic compound VSL#3 far 7 days. To induce sepsis, the mice were injected with lipopolysaccharide OLPS) and D-galactosamine (Ga1N in the presence and absence of the peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibitor GW9662. The mice were killed after 6 hours, and their colons were removed for the measurement of the cytokine production and epithelial function. The functional permeability was assessed by the mannitol. movement and cyclic adenosine monophosphate- dependent chloride secretion in tissue mounted in Ussing chambers. The livers were analyzed for bacterial translocation, cytokine production, histological injury, and PPAR gamma levels. The tissue levels of tumor necrosis factor alpha, interferon gamma, IL-6, and IL-12p35 ribonudeic acid were measured by semiquantitative reverse transcription polymerase chain reaction. Mice injected with LPS/Ga1N demonstrated a breakdown in colonic barrier function, which correlated with enhanced proinflaminatory cytokine secretion, bacterial translocation, and significant hepatic injury. A pretreatment with oral probiotics prevented the breakdown in intestinal barrier function, reduced bacterial translocation, and significantly attenuated liver injury," wrote J. Ewaschuk and colleagues, University of Alberta. The researchers concluded: "The inhibition of PPAR gamma with GW9662 abrogated the protection induced by probiotics Orally administered probiotics prevented liver and intestinal damage in a mouse model of sepsis through a PPAR gamma-dependent mechanism." Ewaschuk and colleagues published their study in Hepatology (Problotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Hepatology, 2007;46(3):841-850). For more information, contact K. Madsen, University of Alberta, Dept. of Medical, 6146 Dental Pharmacy Bldg, Edmonton, AB T6G 2N8, Canada. Publisher contact information for the journal Hepatology is: John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. Keywords: Canada, Edmonton, Biotechnology, Gene Therapy, University of Alberta. This article was prepared by Genetics & Environmental Business Week editors from staff and other reports. Copyright 2007, Genetics & Environmental Business Week via NewsRx.com.
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