Fasting-induced intestinal damage is mediated by oxidative and inflammatory responses.

BACKGROUND: Green tea has been shown to repair fasting-induced mucosal damage in rat intestine. The aim of this study was to elucidate the underlying mechanism. METHODS: Five groups of rats were used. Group 1 had free access to chow diet and water, and those in group 2 were fasted for 3 days. Animals in group 3 were fasted for 3 days, then were allowed drinking water for a further 7 days. Groups 4 and 5 were fasted for 3 days, then given drinking water containing green tea or vitamin E respectively for 7 days. Blood was collected for estimation of total plasma antioxidants, and jejunal samples were used for immunohistochemical analysis of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and for estimation of myeloperoxidase (MPO) activity. RESULTS: Use of green tea was associated with a significant increase in total plasma antioxidants (P < 0.001), and mucosal SOD (P < 0.001), catalase (P = 0.006) and GPx (P = 0.017), but a significant decrease in MPO activity (P < 0.001). Vitamin E produced similar changes, but the effects were smaller. CONCLUSION: Green tea reverses the fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect.

Blockade of tumor necrosis factor-alpha-converting enzyme improves experimental small intestinal damage by decreasing matrix metalloproteinase-3 production in rats.

OBJECTIVE: Tumor necrosis factor (TNF)-alpha-converting enzyme (TACE), which has been purified, regulates maturity of TNF-alpha. Matrix metalloproteinases (MMPs) play a key role in various inflammatory conditions. The incidence of intestinal damage has increased, but the mechanism and treatment have not been well understood. The purpose of this study was to investigate the roles of TACE and MMP in indomethacin (Indo)-induced intestinal damage as well as the therapeutic effects of TACE inhibitor and selective MMP inhibitor (sMMPi) on this intestinal damage in rats. MATERIAL AND METHODS: In the first experiment, serial changes in intestinal ulcers and the production of MMP were investigated. In the second experiment, we assessed the effect of three TACE and/or MMP inhibitors and the production of TNF-alpha, TACE, MMP-3, -9 and tissue inhibitor of MMP (TIMP)-1. The rats were divided into five groups: a control group, and four groups that received Indo alone, Indo plus TACE inhibitor (GM6001), Indo plus a selective MMP-3 inhibitor and Indo plus an MMP-9/13 inhibitor, respectively. RESULTS: MMP-3 was overexpressed at 24 h after Indo administration, when intestinal injury was most prominent macroscopically and microscopically. GM6001 significantly decreased ulcer severity and suppressed MMP-3 in a dose-dependent fashion. The selective MMP-3 inhibitor dose-dependently ameliorated intestinal damage to the same degree as GM6001, but the MMP-9 inhibitor had no effect on the injury. CONCLUSIONS: MMP-3 inhibition ameliorates intestinal damage without apparently affecting either TNF-alpha or TACE production and the dose-response curve suggests that the beneficial effect of the so-called TACE inhibitor is actually mainly mediated via MMP-3 inhibition rather than TNF-alpha inhibition.

The prevalence and severity of intestinal disaccharidase deficiency in human immunodeficiency virus-infected subjects.

BACKGROUND: Gastrointestinal symptoms are distressing features of human immunodeficiency virus (HIV) infection, and management is often empirical, including withdrawal of dietary lactose. We assessed the prevalence and severity of intestinal disaccharidase deficiency in vitro and in vivo. METHODS: Fifty-four HIV-seropositive patients (19 HIV well +/- mild diarrhoea, 7 acquired immunodeficiency syndrome (AIDS) well, and 28 AIDS with diarrhoea) were studied with a combined non-invasive absorption-permeability-disaccharidase test that enables quantitative assessment of the rate of intestinal hydrolysis of lactose, sucrose, and palatinose. Thirty patients had jejunal biopsy specimens suitable for histomorphometric assessment, and 36 had in vitro disaccharidase activity measurement. RESULTS: Patients with HIV (with mild diarrhoea) and AIDS (with and without severe diarrhoea) had frequent but mild histomorphometric changes in jejunal specimens. This was associated with frequent (21%-100%) and often severe in vitro jejunal disaccharidase deficiency. In vivo hydrolysis of lactose, sucrose, and palatinose was impaired in 25%-75% of patients, apart from HIV well patients, who were normal. The prevalence of the in vivo lactase and sucrase deficiency was significantly (P < 0.006) lower than in vitro and severe in about 30%. CONCLUSIONS: Intestinal disaccharidase deficiency is common both in vitro and in vivo in HIV-seropositive patients but sufficiently severe to consider lactose withdrawal only in about a quarter of the patients with AIDS and diarrhoea.

Exposure to ionizing radiation increases responsiveness to neural secretory stimuli in the ferret jejunum in vitro.

Experiments were designed to determine the effects of ionizing radiation on jejunal epithelial function in the ferret in vitro. Basal and stimulated electrolyte transport were determined in Ussing chambers at 0.5, 2, 24 and 48 h post-irradiation. Tissue histamine and 5-hydroxytryptamine levels were measured. Myeloperoxidase activity was also measured as an index of inflammation. Basal short circuit current was reduced at 2 h post-irradiation, but was elevated at 48 h. Basal conductance was significantly increased by 24 and 48 h. Responsiveness to electrical field stimulation was depressed at 0.5 h, and was greater than control by 24 and 48 h post-irradiation. Similarly, short circuit current responses to prostaglandin E2 were depressed at 0.5 h and elevated at 24 h. No significant change was observed in the response to carbachol post-irradiation, indicating that alterations in responsiveness were not likely at the level of the enterocyte. Changes in responsiveness to electrical field stimulation correlated significantly with increases in mucosal mast cell numbers. Myeloperoxidase activity, indicative of neutrophil infiltration, did not increase post-irradiation, nor was there histological evidence of an inflammatory cell infiltrate. There were no changes in tissue histamine or 5-hydroxytryptamine. Histology also revealed little microscopic morphological change from shams in tissue from irradiated ferrets. The results of this study demonstrate effects of irradiation on electrolyte transport in the ferret jejunum. The enhanced neurally evoked electrolyte transport observed at 24-48 h post-irradiation was not correlated with the development of inflammation, but was correlated with changes in mast cell numbers.

Experimental intestinal obstruction in rats. Studies on structure and disaccharidase activities.

An experimental model of congenital intestinal obstruction (CIO) was created in rats by means of fetal intrauterine surgery between the 16th and 20th days of gestation. By the use of a microsurgical technique areas at the mid-jejunum or the jejuno-ileal junction were infarcted by coagulation of mesenteric vessels. Gestation was terminated by Cesarean section within 24 hours before expected term to avoid cannibalism. The structure of the intestinal mucosal cells proximal and distal to the CIO at the light microscopy as well as the ultrastructure level was not changed indicating that the surgical method was successful. The activities of the brush border enzymes, maltase and lactase were significantly reduced distal to the obstruction as compared to controls. Proximal to the obstruction lactase was the only enzyme showing reduced activity in comparison to controls. These findings were not dependent on the localization of the obstruction or when it was performed and suggest that CIO causes selective changes of the biochemical properties of the cell membrane. The results are in agreement with the findings of disaccharidase activities in biopsies taken from human infants with CIO and point to the importance of a normal intestinal passage for the development of brush border enzymes.

Development of wheat-sensitive enteropathy in Irish Setters: biochemical changes.

Biochemical changes in the small intestine during development of naturally acquired wheat-sensitive enteropathy of Irish Setters were investigated. To distinguish primary biochemical abnormalities from secondary effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were sequentially obtained between weaning and 1 year of age; specific activity and reorientating sucrose density-gradient distribution of organelle marker enzymes were determined. Major primary biochemical abnormalities were not detected in affected progeny. In affected dogs fed wheat, there was a selective, but secondary, loss of the brush border alkaline phosphatase and aminopeptidase N activities. This loss was associated with the development of partial villus atrophy, but represented a specific effect of dietary wheat on the brush border, not merely a nonspecific effect of mucosal damage, because other brush border enzymes, including disaccharidases, were not similarly affected. Increased soluble activities of lysosomal and peroxisomal marker enzymes late in the disease process may represent alterations in these 2 organelles as a secondary consequence of mucosal damage.

[A rapid test for the analysis of lactase and sucrase activity in the jejunum (a comparative study)]. / A jejunum laktáz és szaharáz aktivitásának kimutatása gyorsteszttel. (Osszehasonlítóvizsgálat)]

Jejunal lactase and sucrase activities were demonstrated in biopsy specimens obtained endoscopically using a rapid test which had been developed previously. The results were compared with enzyme activities determined by Dahlquist's method. The data suggest that the rapid test is suitable for the demonstration about the presence of lactase and sucrase, and the results are correlated with enzyme activities measured by assay. The main advantage of the test, that it is rapid, simple and cheap, no special equipments are necessary, so it can be used in every endoscopic department.

Effect of glucocorticoid on piglet jejunal mucosa during acute viral enteritis.

We measured the effect of pharmacological doses of glucocorticoid on piglet jejunal structure and function during acute viral diarrhea. Weaned piglets, infected experimentally with transmissible gastroenteritis virus, a coronavirus that induces a diarrheal illness similar to human rotavirus infection, received methylprednisolone (30 mg/kg) or saline intramuscularly at 48 and 72 h after infection; noninfected littermate controls were similarly injected with methylprednisolone. Animals were killed at 96 h, at the height of diarrhea, and jejunal epithelium was studied in vitro. Transmissible gastroenteritis, as expected, induced structural, enzyme, and Na transport abnormalities. Methylprednisolone did not affect small intestinal structure or function of noninfected control piglets. In transmissible gastroenteritis-infected piglets, jejunal villi were longer and glucose-facilitated Na absorption was greater after methylprednisolone than after saline treatment. Increased glucose stimulation of Na flux in vitro in the methylprednisolone-treated infected group was not attributable to enhanced Na+-K+-ATPase activity and occurred despite persistence of the virus within mucosal cells, shown by immunofluorescence microscopy. In this piglet model of viral diarrhea, early regeneration of absorptive surface that precedes recovery of disaccharidase function is accelerated by glucocorticoid therapy.

Ultrastructural and biochemical changes in human jejunal mucosa associated with enteropathogenic Escherichia coli (0111) infection.

A case of prolonged diarrhoea following Escherichia coli 0111 gastroenteritis is reported. Electron microscopy of the jejunal biopsy revealed effacement of the brush border and attachment of bacteria by pedestal formation. Specific activities of brush border enzymes showed marked depression of disaccharidases, zinc-resistant alpha-glucosidase, and alkaline phosphatase. In contrast, marker enzymes for basolateral membranes and endoplasmic reticulum were unaffected. The biochemical changes support the pathogenic mechanism suggested by ultrastructural studies previously reported.