Journal ArticleDOI
Role of alkaline phosphatase in colitis in man and rats
A Tuin,Klaas Poelstra,A. de Jager-Krikken,Lisette Bok,W. Raaben,M. P. Velders,Gerard Dijkstra +6 more
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The rat model demonstrates that oral administration of active iAP enzymes in the intestinal tract results in a significant reduction of inflammation, which provides new insight on IBD pathology and a novel treatment approach to this severe inflammatory disease.Abstract:
Background & Aims: Crohn9s disease (CD) and ulcerative colitis (UC) are chronic multifactorial inflammatory bowel diseases with unknown etiology, but a deregulated mucosal immune response to gut-derived bacterial antigens is thought to be involved. Toll-like receptor ligands, especially lipopolysaccharide (LPS), contribute to the maintenance of the disease. We have previously shown that the enzyme alkaline phosphatase (AP) is able to detoxify LPS and the aim of this study was to examine a possible role in inflammatory bowel diseases. Methods: Intestinal AP (iAP) mRNA expression and LPS-dephosphorylation in intestinal biopsies of control persons and IBD patients were examined, and we subsequently studied the effect of orally administered iAP-tablets on the progression of dextran sodium sulphate-induced colitis in rats. Results: In healthy persons, iAP mRNA and enzyme activity was high in the ileum relative to the colon. In UC and Crohn9s patients iAP mRNA expression was found markedly reduced when inflamed tissue was compared to non-inflamed tissue. Oral administration of iAP-tablets to colitic rats resulted in a significant attenuation of colonic inflammation as reflected by reduced mRNA levels for TNFα, IL-1β, IL-6 and iNOS, a reduced iNOS-staining and inflammatory cell influx, and a significantly improved morphology of the intestinal wall. Conclusions: The present study shows that epithelial iAP mRNA expression is reduced in both UC and Crohn9s patients. The rat model demonstrates that oral administration of active iAP-enzymes in the intestinal tract, results in a significant reduction of inflammation. This provides new insight on IBD pathology and a novel treatment approach to this severe inflammatory disease.read more
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Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials.
Gordon S. Doig,Gordon S. Doig,Philippa T. Heighes,Fiona Simpson,Elizabeth A. Sweetman,Andrew Davies +5 more
TL;DR: The detection of a statistically significant reduction in mortality is promising, overall trial quality was low, trial size was small, and the findings may be restricted to the patient groups enrolled into included trials.
Journal ArticleDOI
Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet
TL;DR: IAP has a pivotal role in intestinal homeostasis and its activity could be increased through the diet, especially true in pathological situations in which the involvement of commensal bacteria is suspected and when intestinal AP is too low to detoxify a sufficient amount of bacterial lipopolysaccharide.
Journal ArticleDOI
Intestinal alkaline phosphatase: novel functions and protective effects
TL;DR: The IAP gene family has a strong evolutionary link to food-driven changes in gastrointestinal tract anatomy and microbiota composition, and stimulation of IAP activity by dietary intervention is a goal for preserving gut homeostasis and health by minimizing low-grade inflammation.
Journal ArticleDOI
Critical review evaluating the pig as a model for human nutritional physiology.
Eugeni Roura,S.J. Koopmans,Jean-Paul Lallès,Isabelle Le Huërou-Luron,Nadia de Jager,T. Schuurman,David Val-Laillet +6 more
TL;DR: Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake and the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability.
Journal ArticleDOI
Animal models of ulcerative colitis and their application in drug research
TL;DR: This review focuses on common animal models that are particularly useful for the study of UC and its therapeutic strategy and recent reports of the latest compounds, therapeutic strategies, and approaches tested on UC animal models are discussed.
References
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Journal ArticleDOI
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
Journal ArticleDOI
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Yasunori Ogura,Denise K. Bonen,Naohiro Inohara,Dan L. Nicolae,Felicia F. Chen,Richard Ramos,Heidi M. Britton,Thomas M. Moran,Reda Karaliuskas,Richard H. Duerr,Jean-Paul Achkar,Steven R. Brant,Theodore M. Bayless,Barbara S. Kirschner,Stephen B. Hanauer,Gabriel Núñez,Judy H. Cho +16 more
TL;DR: It is shown that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease, and a link between an innate immune response to bacterial components and development of disease is suggested.
Journal ArticleDOI
Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.
Stephen E. Girardin,Ivo G. Boneca,Jérôme Viala,Mathias Chamaillard,Agnès Labigne,Gilles Thomas,Dana J. Philpott,Philippe J. Sansonetti +7 more
TL;DR: It is shown here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptIDoglycan motif common to all bacteria.
Journal ArticleDOI
Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2 IMPLICATIONS FOR CROHN′S DISEASE
Naohiro Inohara,Yasunori Ogura,Ana Fontalba,Olga Gutierrez,F. Pons,Javier Crespo,Koichi Fukase,Seiichi Inamura,Shoichi Kusumoto,Masahito Hashimoto,Simon J. Foster,Anthony P. Moran,Jose L. Fernandez-Luna,Gabriel Núñez +13 more
TL;DR: NOD2 mediates the host response to bacterial muropeptides derived from peptidoglycan, an activity that is important for protection against Crohn's disease and has implications for understanding adjuvant function and effective vaccine development.
Journal ArticleDOI
Differential Alteration in Intestinal Epithelial Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory Bowel Disease
Elke Cario,Daniel K. Podolsky +1 more
TL;DR: The data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that alterations in the innate response system may contribute to the pathogenesis of these disorders.
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