Comparison of Magnetic Resonance Enterography Global Score (MEGS) with indices of Crohn's disease activity in South Asian population.

PURPOSE: Assessment of disease activity in Crohn's helps predict important clinical outcomes. Among the various modalities available to assess disease activity, magnetic resonance enterography (MRE) is considered a safe and reliable imaging option. Various MRE-based scoring systems have been developed to measure disease activity, one of which being the MRE global score (MEGS). We aimed to correlate MEGS with some of the important indices of Crohn's disease activity. METHODOLOGY: Crohn's disease patients referred for MRE were included in the study. Along with demographic profile and relevant investigations, MRE parameters related to MEGS were also assessed. RESULT: A total of 47 patients were recruited for the study. Their median age was 34 years (range 18-68 years), and male:female ratio was 16:31. There was modest positive correlation between MEGS and faecal calprotectin (r = 0.3, p = 0.04), CRP level (r = 0.34, p = 0.02) and Harvey Bradshaw index (r = 0.3, p = 0.043), respectively. However, there was strong correlation between segmental MEGS and Simple Endoscopic Score in those with terminal ileal disease (r = 0.81, p < 0.001). Mural thickness was the only MRE parameter that correlated with active disease (OR - 1.35, 95% CI 1.01, 1.81, p = 0.041) on multivariate analysis. There was moderate inter-observer agreement (Lin's r = 0.78, p < 0.001). CONCLUSION: MEGS showed modest correlation with indices of Crohn's disease activity which corroborates the complementary role of MRE in management of such patients.

An Unusual Presentation of Hemorrhagic Disease in an Infant: A Probable Case of Abetalipoproteinemia.

We report a probable case of abetalipoproteinemia in an infant who presented with unusual symptoms of late-onset vitamin K deficiency. Abetalipoproteinemia is a rare autosomal recessive disease caused by mutation of the microsomal triglyceride transfer protein gene, resulting in the absence of microsomal triglyceride transfer protein function in the small bowel. It is characterized by the absence of plasma apolipoprotein B-containing lipoproteins, fat malabsorption, hypocholesterolemia, retinitis pigmentosa, progressive neuropathy, myopathy, and acanthocytosis. A biopsy of the small intestine characteristically shows marked lipid accumulation in the villi of enterocytes. Large supplements of fat-soluble vitamins A, D, E, and K have been shown to limit neurologic and ocular manifestations. Dietary fat intake is limited to medium-chain triglycerides.

Protective role of aspirin, vitamin C, and zinc and their effects on zinc status in the DMH-induced colon carcinoma model.

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria.

Spontaneous bacterial peritonitis is a major cause of mortality after liver cirrhosis. Altered permeability of the mucosa and deficiencies in host immune defenses through bacterial translocation from the intestine due to intestinal bacterial overgrowth have been implicated in the development of this complication. Molecular mechanisms underlying the process are not well known. In order to understand mechanisms involved in translocation of bacteria, this study explored the role of oxidative stress in mediating changes in intestinal mucosal glycosylation and luminal bacterial content during cirrhosis. CCl4-induced cirrhosis in rats led to prolonged oxidative stress in the intestine, accompanied by increased sugar content of both intestinal brush border and surfactant layers. This was accompanied by changes in bacterial flora in the gut, which showed increased hydrophobicity and adherence to the mucosa. Inhibition of xanthine oxidase using sodium tungstate or antioxidant supplementation using vitamin E reversed the oxidative stress, changes in brush border membrane sugar content, and bacterial adherence. In conclusion, oxidative stress in the intestine during cirrhosis alters mucosal glycosylation, accompanied by an increased hydrophobicity of luminal bacteria, enabling increased bacterial adherence onto epithelial cells. This might facilitate translocation across the mucosa, resulting in complications such as spontaneous bacterial peritonitis.

Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB.

Butyrate enemas have been demonstrated to ameliorate inflammation in ulcerative colitis. The mechanism of this protective effect of butyrate is not known, and this study examines the effect of butyrate on epithelial function, inducible heat shock protein 70 (HSP70) expression, and NF-kappaB activation in experimental colitis. Colitis was induced in rats by oral dextran sulfate sodium (DSS) and by butyrate or saline enemas. Mucosal barrier function was assessed by electrical resistance and [14C]mannitol permeability. HSP70 production was determined by [35S]methionine labeling, Western blot analysis, and immunohistochemistry. Activation of heat shock factors (HSFs) and NF-kappaB was evaluated by EMSA. Butyrate showed a significant protection against the decrease in cell viability, increase in mucosal permeability, and polymorphonuclear neutrophil infiltration seen in DSS colitis. Butyrate inhibited HSP70 expression in DSS colitis and also inhibited the activation of HSF and NF-kappaB. Thus butyrate enema was found to be cytoprotective in DSS colitis, an effect partly mediated by suppressing activation of HSP70 and NF-kappaB.

Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation.

BACKGROUND: The small intestine is susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals, leading to mucosal damage. Heat preconditioning has been shown to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on surgical manipulation-induced intestinal mitochondrial alterations. METHODS: Control and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from isolated enterocytes and structural and functional alterations were assessed. RESULTS: Surgical manipulation of the intestine resulted in mitochondrial alterations as seen by ultrastructural changes and altered lipid composition. Mitochondria were functionally impaired as evidenced by altered calcium flux, decreased respiratory control ratio, and increased tetrazolium dye reduction and swelling. Along with this, biochemical alterations such as increased lipid and protein oxidation were seen following surgical manipulation. Mild heat preconditioning of the animal prevented these damaging effects. CONCLUSIONS: These studies suggest that stress in the small intestine due to surgery can affect enterocyte mitochondrial structure and function and these effects can be prevented by mild whole body hyperthermia prior to surgery.