Therapeutic use of a receptor mimic probiotic reduces intestinal Shiga toxin levels in a piglet model of hemolytic uremic syndrome

BACKGROUND: Hemolytic uremic syndrome (HUS) is a systemic and potentially fatal complication of gastroenteritis secondary to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infection characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage. Shiga toxin (Stx), the toxin principle in HUS, is produced locally within the gut following EHEC colonization and is disseminated via the vasculature. Clinical development of HUS currently has no effective treatment and is a leading cause of renal failure in children. Novel post-exposure therapies are currently needed for HUS; therefore, the purpose of this study was to investigate the efficacy of a Stx receptor mimic probiotic in a porcine model of HUS. Edema disease, an infection of swine caused by host adapted Shiga toxin-producing Escherichia coli (STEC) and mediated by Shiga toxin 2e (Stx2e), shares many pathogenic similarities to HUS. In this study, three-week old piglets were inoculated with STEC and 24 hours later treated twice daily with a probiotic expressing an oligosaccharide receptor mimic for Stx2e to determine if the probiotic could reduce intestinal toxin levels. METHODS: Piglets were orally inoculated with 10(10) CFU of STEC strain S1191 eight days after weaning. Beginning day 1 post-inoculation, piglets were treated orally twice daily with 5 × 10(11) CFU of either the receptor mimic probiotic or a sham probiotic for 10 days. Intestinal Stx2e levels were assessed daily via Vero cell assay. The efficacy of the probiotic at reducing intestinal Stx2e, vascular lesions, and clinical disease was evaluated with repeated measures ANOVA and Fisher's exact test as appropriate. RESULTS: The probiotic significantly reduced intestinal Stx2e, as reflected by decreased fecal toxin titers on days 3-8 post-inoculation (p < 0.01). Despite this reduction in intestinal toxin levels, however, the probiotic failed to reduce the incidence of vascular necrosis in target organs and had no effect on clinical disease. CONCLUSIONS: The data suggest that post-exposure treatment with a Stx-binding probiotic is effective in reducing intestinal toxin burden. Future studies could target this approach for possible development of post-exposure interventions.Shannon J Hostetter, Amy F Helgerson, James C Paton, Adrienne W Paton, and Nancy A Cornic

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The following report presents results of the Tascotal detailed geochemical survey for Trans-Pecos, Texas. Field and laboratory data are presented for 337 groundwater and 611 stream sediment samples

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Documentation outlining characteristics of field data samples taken in the Buffalo-Lignite detail area

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The following report provides results from a geochemical survey for Thomas Range-Wasatch, Utah. Field and laboratory data are presented for 15 groundwater and 79 stream sediment samples

Bedrock erosion by root fracture and tree throw: A coupled biogeomorphic model to explore the humped soil production function and the persistence of hillslope soils

In 1877, G. K. Gilbert reasoned that bedrock erosion is maximized under an intermediate soil thickness and declines as soils become thinner or thicker. Subsequent analyses of this “humped” functional relationship proposed that thin soils are unstable and that perturbations in soil thickness would lead to runaway thinning or thickening of the soil. To explore this issue, we developed a numerical model that simulates the physical weathering of bedrock by root fracture and tree throw. The coupled biogeomorphic model combines data on conifer population dynamics, rootwad volumes, tree throw frequency, and soil creep from the Pacific Northwest (USA). Although not hardwired into the model, a humped relationship emerges between bedrock erosion and soil thickness. The magnitudes of the predicted bedrock erosion rates and their functional dependency on soil thickness are consistent with independent field measurements from a coniferous landscape in the region. Imposed perturbations of soil erosion during model runs demonstrate that where bedrock weathering is episodic and localized, hillslope soils do not exhibit runaway thinning or thickening. The pit-and-mound topography created by tree throw produces an uneven distribution of soil thicknesses across a hillslope; thus, although episodes of increased erosion can lead to temporary soil thinning and even the exposure of bedrock patches, local areas of thick soils remain. These soil patches provide habitat for trees and serve as nucleation points for renewed bedrock erosion and soil production. Model results also suggest that where tree throw is a dominant weathering process, the initial mantling of bedrock is not only a vertical process but also a lateral process: soil mounds created by tree throw flatten over time, spreading soil over bedrock surfaces

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Results of the Chinati Mountains project area of the detailed geochemical survey fro Trans-Pecos, Texas are reported

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Results of the Dryden project area of the detailed geochemical survey for Trans-Pecos, Texas are reported

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Results of the Stillwell Mountains project area of the detailed geochemical survey for Trans-Pecos, Texas are reported