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Necrotizing enterocolitis: A multifactorial disease with no cure

World Journal of Gastroenterology 2008年第14期14卷 2142-2161页

作者： kareena l schnabl John E Van Aerde Alan BR Thomson Michael T Clandinin Nutrition and Metabolism Research Groups Department of Medicine University of Alberta Edmonton T6G 2P5 Canada Department of Pediatrics University of Alberta Edmonton T6G 2P5 Canada Department of Medicine Division of Gastroenterology University of Alberta Edmonton T6G 2P5 Canada Alberta Institute for Human Nutrition University of Alberta Edmonton T6G 2P5 Canada

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

关键词： Necrotizing enterocolitis Diagnosis Pathogenesis Prevention Disease models Vasoactive/ inflammatory mediators

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Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2015年第35期21卷 10080-10090页

作者： John J Miklavcic Glen K Shoemaker Vera C Mazurak M Tom Clandinin Tasha Dl Hart kareena l schnabl Gordon M lees Bodil MK larsen Oliver F Bathe Alan BR Thomson M Tom Clandinin Alberta Institute for Human Nutrition University of Alberta Edmonton AB T6G 2R1 Canada Department of laboratory Medicine and Pathology University of Alberta Edmonton AB T6G 2B7 Canada Division of General Surgery University of Alberta Edmonton AB T6G 2B7 Canada Alberta Health Services Edmonton AB T6G 2B7 Canada Alberta Health Services Calgary AB T2N 4N2 Canada Division of Gastroenterology Western University London ON N6A 5A5 Canada Department of Medicine University of Alberta Edmonton AB T6G 2B7 Canada

AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESUlTS: Relative GM3 ganglioside content was 2-fold higher(P lammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P l intestine exhibited 3-fold higher(P lative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P lative content of HEXA in IBD intestine was increased 1.7-fold(P ld

关键词： Ganglioside Phospholipid Fatty acid lipid Inflamma

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