1. To establish the speed on onset of jejunal and ileal mucosal hypoplasia and hypofunction in parenterally fed rats, we measured three indices of mucosal mass, three mucosal enzymes and quantitative histology after 3, 6, 10 and 15 days of total parenteral nutrition and compared the results with those in two orally fed control groups, one with and one without intravenous catheters and metabolic cage restraint. The kinetics of galactose absorption in vivo were also measured after 10 days of total parenteral nutrition and in both control groups. 2. The most striking decrease in both jejunal and ileal mucosal wet weight and protein and DNA content per 10 cm length of intestine, occurred after only 3 days of total parenteral nutrition; thereafter the mean values showed only a slight further decrease. 3. The results of the morphometric studies showed that the hypoplasia affected the villi slightly more than the crypts. Within 3 days of starting total parenteral nutrition, mean jejunal mucosal thickness decreased by 16% and after 15 days it had fallen by 28%. The ileum showed similar, although less marked, changes. In the jejunum (not the ileum) modest cellular hypotrophy accompanied the mucosal hypoplasia; there were more epithelial cells/unit length of mid-villus and there was more DNA per g of mucosa in the total parenteral nutrition group than in the control group of rats. 4. Jejunal galactose absorption from the 16, 32 and 64 mmol/l solutions was significantly less in the 10-day total parenteral nutrition rats than in the controls, the apparent Vmax. being five times greater in the orally fed animals. The apparent Michaelis constant (Km) was also significantly less than normal in the jejunum of the parenterally fed rats, suggesting increased affinity of the hypothetical carrier for galactose, perhaps as a result of functionally hypermature cells. 5. Mucosal alkaline phosphatase and catalase activities per unit length of intestine decreased and alpha-D-glucosidase activity increased in the jejunum and ileum of the total parenteral nutrition rats. 6. These results show that during total parenteral nutrition, the ileum and particularly the jejunum show marked reductions in mucosal mass and function after only 3 days of total parenteral nutrition and that there is a more gradual and progressive loss of mucosal mass thereafter up to 15 days.
An abnormal metabolism of histamine has been suspected in urticaria and the role of diamine oxidase (DAO: histaminase) is therefore of interest. We have studied DAO activity in plasma and jejunal biopsy material and have measured the post-heparin DAO release in 11 control subjects and nine with recurrent urticaria, three of whom had had concurrent episodes of abdominal pain. Two of the nine urticaria subjects had only a minimal rise in plasma DAO activity after heparin, three had a response which was at the lower end of the normal range, and four were normal. In four out of five cases in which jejunal biopsy activity was obtained, there was concordance between mucosal DAO activity and the post-heparin plasma DAO response. Those with abdominal symptoms had abnormally low mucosal DAO activity and the subject who was most severely affected had proven episodes of small bowel oedema.
The aim of this study was to assess the effect inhibiting diamine oxidase (DAO) activity on intestinal adaptation after 80% proximal small bowel resection in the rat. Aminoguanidine (AG), a DAO inhibitor, was administered subcutaneously (25 mg kg-1 day-1) to rats for 11 days after small bowel transection (n = 6) or resection (n = 6). Two additional groups of animals (n = 6) served as transection or resection controls and received normal saline subcutaneously for the same period. On day 12 after operation, the animals were sacrificed, mucosal homogenates prepared from the ileal remnants (or from the control ileum), analysed for DAO and ornithine decarboxylase (ODC) activities, and the concentrations of the polyamines putrescine, spermidine, spermine, and the indices of mucosal mass (wet weight, protein and DNA) measured. The results were expressed both per unit length intestine and per milligram mucosal DNA. AG treatment completely inhibited DAO activity in both the transection control and resected rats. In the AG-treated resection group, inhibition of DAO activity was accompanied by increases (p < 0.005) in all three indices of mucosal mass (wet weight, protein and DNA per centimetre intestine), putrescine concentrations (p < 0.05) and ODC activity per centimetre intestine (p < 0.001) when compared with the saline-treated resection controls. The results of this study suggest that inhibition of the putrescine-degrading enzyme, DAO, enhances the adaptive response to intestinal resection. Therefore, DAO may play a major role in regulating adaptive intestinal mucosal growth. Furthermore, inhibition of DAO activity could be important therapeutically in patients with the short bowel syndrome.
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