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Induction and repression of genes of the rat small intestine mucosa with excess and insufficiency of alimentary iron.

Three-month-old Wistar rats were fed with either an iron-deficient diet for 21 days or an iron-excessive diet for 10 days. Fifty thousand clones of a cDNA library of small intestine mucosa were hybridized with two radioactive samples synthesized on mRNA from the small intestine of rats fed with iron-excessive or iron-deficient diets. As a result, genes were found with mRNA level depending on the content of alimentary iron. Iron deficiency increased the mRNA level of genes of apolipoprotein AIV and class 1 antigen and decreased the mRNA level of the apolipoprotein AI gene and of an unknown gene, while no change was found in the mRNA level of the gene of fatty acid-binding protein. Excess of dietary iron resulted in the increase in mRNA of this gene and in a decrease in the apolipoprotein AI gene and in the unknown gene. The mRNA of apolipoprotein AIV did not change. The data indicate that changes in the level of alimentary iron influence the expression of genes involved in metabolism of lipids.

Animals↗

Carnitine and carnitine transferases in the intestinal mucosa of suckling rats.

Carnitine acetyltransferase and palmitoyltransferase activity in the mucosa of the small intestine of rats rises after birth and falls at the time of weaning. The carnitine contents of the mucosa (free, acetyl-, palmitoyl- and total) decrease postnatally, reaching adult levels at the time of weaning. Orally administered 14C-carnitine is only slowly absorbed so that radioactivity is still high in plasma and organs 6 h later, whereas label given subcutaneously disappears from the plasma and tissues more rapidly. The intestinal mucosa also takes up carnitine from 14C-carnitine administered subcutaneously. It is concluded that carnitine plays an important role in the gut of suckling rats.

Acetyltransferases↗

Mycobacterium avium subsp. paratuberculosis enters the small intestinal mucosa of goat kids in areas with and without Peyer's patches as demonstrated with the everted sleeve method.

The main lesions of paratuberculosis in ruminants are in the small intestine. Previous studies have shown that the bacterium enters the small intestine through M cells found in the follicle-associated epithelium lining the domes of the Peyer's patches. The everted sleeve method, devised for the in vitro study of intestinal absorption, was used in this study to investigate the uptake of Mycobacterium avium subsp. paratuberculosis in goat intestine. Everted small intestinal sleeves of goat kids, prepared from areas with and without Peyer's patches, were incubated for 60 min in 3H-labeled bacterial solution. The results of this study imply that the bacteria can enter the intestinal mucosa of the jejunum, both in areas with and without Peyer's patches. These findings indicate, therefore, that M. avium subsp. paratuberculosis bacteria not only enter through M cells but also through enterocytes.

Animals↗

Cell cultures as models for drug absorption across the intestinal mucosa.

This review deals with cell culture models for studies of drug absorption across the intestinal mucosa. The selection of appropriate cells and cell culture conditions is discussed, guidelines for the characterization of the cell models are presented, and the intestinal barriers to drug absorption are discussed and compared with those in the cell culture models. Finally, recent applications of the cell culture models in drug and peptide absorption and metabolism studies are reviewed.

Cells, Cultured↗

Selective affinity of dimethyl sulphoxide (DMSO) and 2-amino-4-phenylsulphonylbenzenesulphonamide (NSD 3004) for the large intestinal mucosa of mice.

Whole-body autoradiography of 14C-labelled dimethyl sulphoxide and 35S-labelled 2-amino-4-phenylsulphonylbenzenesulphonamide revealed a selective accumulation of labelled substance in the large intestinal mucosa of mice. The mechanism of accumulation is discussed with regard to previous results on sulphone-containing compounds with tissue-specific distribution patterns.

Animals↗

Peptide hydrolase activity of human intestinal mucosa in adult coeliac disease.

The levels of two peptide hydrolases were studied in intestinal mucosa from normal subjects, patients with untreated coeliac disease, and treated patients. The mucosa from the untreated patients had significantly reduced activity against glycyl-glycine and leucylleucine. No such difference was found for the treated patients and it was concluded that the reduction in peptidase activity was secondary to the mucosal damage.

Adult↗

Immune response of the intestinal mucosa to cholera toxoid.

The intestinal immune response to cholera toxoid was studied in dogs and rats. Oral or intraperitoneal priming followed by duodenal boosting with toxoid reulted in antitoxin-containing plasma cells (ACC) in jejunal lamina propria of rats. Priming and boosting by the intraperitoneal route alone induced almost no jejunal response. Lamina propria ACC were derived largely from migrating immunoblasts, which appeared earlier among thoracic duct lymphocytes. Protection of dogs after repeated subcutaneous immunization with toxoid was mediated largely, or entirely, by serum-derived antibody. The sequence of subcutaneous priming and repeated oral boosting induced longer lasting protection mediated almost entirely by the local intestinal immune mechanism. The results suggest that cholera immunization should be specifically designed to stimulate the intestinal immune mechanism and that the subcutaneous oral immunizing sequence may be an efficient way to do this.

Administration, Oral↗

Isolation of deoxyribonuclease II from bovine intestinal mucosa.

Musoca from bovine small intestine was homogenized in Krebs-Ringer phosphate buffer, pH 7.8 the homogenate centrifuged at 16300 X g, and the supernatant solution filtered through cheesecloth to remove lipid material. The filtrate was centrifuged at 105000 X g and the supernatant solution chromatographed on DEAE-cellulose. The major peak of DNase II activity, eluted with 20 mM phosphate - 10 mM EDTA buffer, pH 7.8, was purified further by ion-exchange chromatography on CM-cellulose and gel filtration on Sephadex G-100. The enzyme was purified 78-fold in 13% yield. Evidence was adduced to indicate that the second minor peak of DNase II activity, eluted from the DEAE-cellulose by a potassium chloride gradient in the 20 mM phosphate - 10 mM EDTA buffer, was an artifact arising from the presence of significant amounts of DNA in the 105000 X g supernatant. The enzyme degraded DNA endonucleolytically to 3'-PO4, 5'-OH oligonucleotides and is similar in its properties to DNase II from other tissues.

Animals↗

[Alkaline phosphatases in human feces, intestinal mucosa and bile, and the occurrence of 5'-nucleotidase in feces (author's transl)].

Alkaline phosphatase (EC 3.1.3.1) in extracts of human feces resembles alkaline phosphatase in extracts of duodenal mucosa, except for its electrophoretic mobility in starch gel. It is very probable that the normal feces alkaline phosphatase derives from intestinal mucosa. Gall bladder alkaline phosphatase, which is markedly different, has not been found in normal feces. Some patients with acute viral hepatitis or protozoasis excrete an alkaline phosphatase which resembles gall bladder alkaline phosphatase and has the characteristics of 5'-nucleotidase (EC 3.1.3.5). The appearance of this enzyme correlates with low total alkaline phosphatase activity of the excreta.

Adult↗

Fat absorption and triglyceride synthesis and secretion by cultured human intestinal mucosa.

Uptake and esterification of fatty acids from micellar lipid solutions by human small intestinal mucosa was studied in vitro. Small bowel biopsies, obtained during endoscopy, were incubated at 37 C in RPMI 1640 medium containing various concentrations of micellar lipids (sodium taurocholate, oleate and monoolein). Oleate uptake from the micellar solution was enhanced and correlated positively with micellar ingredient concentration at a range of 2.4 to 9.6 mmol/l taurocholate. Triglyceride (TG) synthesis during incubation was affected by micellar bile salt concentration, as well as by micellar concentration of oleate and monoolein. At a high concentration of bile salt, TG synthesis was decreased. Boiling of tissue specimens resulted in complete inhibition of TG synthesis, but did not affect oleate uptake. When intestinal biopsy tissue was incubated in a micellar lipid solution and subsequently organ-cultured, gradual depletion of tissue oleate and TG content was evident, concomitant with TG secretion to the medium. TG secretion persisted during 24 h of organ culture, but decreased with time. Intestinal TG synthesis was not affected by methylprednisolone, pentagastrin, nicotinic acid or insulin, but was decreased by cimetidine.

Cimetidine↗

Intestinal mucosa of celiacs in remission is unable to abolish toxicity of gliadin peptides on in vitro developing fetal rat intestine and cultured atrophic celiac mucosa.

Subfraction 2R of fraction 9 from a peptic-tryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1-0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction 2R, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission.

Animals↗

The influence of gut function on lymphoid cell populations in the intestinal mucosa of lambs.

The number and type of lymphoid cells in the intestinal mucosa of lambs change during the first weeks after birth. The influence of gut function on these changes was examined by comparing the evolution of lymphoid cell populations in normal ileum with that in lengths of ileum which had been isolated surgically from the functional intestinal tract of the lamb before birth. The isolated lengths of ileum had a normal blood and nerve supply and they remained healthy throughout a period of at least 2 years, although they did not have a normal histological development. In comparison with normal ileum, the villi of the isolated ileal segments were much smaller and there were many fewer intraepithelial lymphocytes; the lamina propria had significantly fewer lymphocytes than the functional ileum and only a few plasma cells. When isolated ileal segments were reconnected into the intestinal tract after having been isolated from it for 1-3 months, the histology of the mucosa reverted to that of the normal gut, with the same number and types of lymphoid cells. Radiolabelled lymphoblasts collected from intestinal lymph and injected intravenously accumulated to only a small extent in isolated segments of ileum compared with either the normal or the reconnected segments of ileum. This suggested that the paucity of lymphocytes in the mucosa of the isolated segments was due to a reduced extravasation of these cells there. The influence which the gut contents exert on the lymphoid cell population in the mucosa is probably associated with antigenic stimulation but may also be related to other factors concerned in the normal digestive functions of the gut.

Animals↗

T lymphocytes and immunoglobulins in small and large intestinal mucosa in children with ulcerative colitis.

In 52 children, aged 4-16 years, with ulcerative colitis, behaviour of A,M,G,E globulins and T lymphocytes in the small and large intestinal mucosa was evaluated. The investigations were performed both in the acute phase and remission of the disease. In the final stage of the disease, numerous plasma cells with intensive reaction to IgA and IgM were found in the stroma, while on the epithelial surface they were less marked. An intensive reaction to IgA was observed in remission. Reaction to T lymphocytes was found in single mononuclear stroma cells both in the acute phase and in remission.

Adolescent↗

Role of alkaline phosphatase in phosphate uptake into brush border membrane vesicles from human intestinal mucosa.

In order to elucidate the physiological function of intestinal alkaline phosphatase, the characteristics of human intestinal alkaline phosphatase bound to brush border membrane vesicles were compared under optimal and physiological pHs. The Km value of this enzyme towards p-nitrophenylphosphate at the physiological pH was lower than that at the optimal pH. At the physiological pH, phosphate, arsenate and vanadate competitively inhibited the alkaline phosphatase activity, as they did at optimal pH, and the K1 values of these inhibitors at the physiological pH were also lower than those at the optimal pH. The effects of various inhibitors and antibody to human intestinal alkaline phosphatase on phosphate uptake into brush border membrane vesicles were investigated. The results indicated that phosphate uptake was affected by various inhibitors and the antibody to human intestinal alkaline phosphatase, but L-homoarginine, levamisole, and ouabain had no effect. From the above findings, it is strongly suggested that human intestinal alkaline phosphatase may function as a phosphate binding protein at low phosphate concentrations under physiological conditions.

Alkaline Phosphatase↗

Ethanol inhibits triglyceride synthesis and secretion by human small intestinal mucosa.

We studied the effect of ethanol on human intestinal lipid absorption and on triglyceride synthesis and secretion. Human duodenojejunal biopsy specimens were incubated in a micellar lipid solution containing carbon 14-labeled oleate in the presence of ethanol 0.1%, 1.0%, and 5.0% (vol/vol). Tissue triglyceride synthesis was significantly decreased by 52.0% +/- 7.7%, 57.0% +/- 9.0%, and 81.3% +/- 4.0% (mean +/- SEM), respectively, when compared with triglyceride synthesis by control biopsy specimens incubated in the absence of ethanol. Tissue levels of oleate were increased in biopsy specimens incubated in the presence of ethanol by 90% +/- 30% and 115% +/- 5% for ethanol concentrations of 1.0% and 5.0% (vol/vol), respectively (P less than 0.02). At ethanol concentration of 0.01%, no change in tissue oleate or triglyceride levels was noted. The effect of 1.0% and 5.0% ethanol on triglyceride synthesis may reflect in large part their significant increase of the medium osmolarity. However, the osmolarity of the medium containing 0.1% ethanol was similar to that of the ethanol-free medium, and its effect is therefore probably specific. Duodenojejunal biopsy specimens were also preincubated for 30 minutes in a micellar lipid solution containing 14C-oleate, and subsequently were organ cultured in micellar-free medium in the presence or absence of ethanol 1.0% (vol/vol). During organ culture, the decrease in tissue oleate levels was similar in biopsy tissue cultured in the presence or absence of ethanol. However, in the presence of ethanol, triglyceride secretion to the organ culture medium was reduced by 49.9% +/- 11.1% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenum↗

Prostaglandin E1 maintains structural integrity of intestinal mucosa and prevents bacterial translocation during experimental obstructive jaundice.

The absence of bile in the gut lumen induces mucosal injury and promotes bacterial translocation (BT). Prostaglandin E (PGE) has a protective effect on the mucosal layer of the alimentary tract. We hypothesize that PGE1 may prevent BT by its beneficial action on the mucosa of the small bowel. Thirty Wistar albino rats were divided equally into 3 groups; Group 1 (control) underwent sham laparotomy, group 2 obstructive jaundice (OJ) and group 3 (OJ + PGE1) underwent common bile duct (CBD) ligation and transection. Groups 1 and 2 received; 1 mL normal saline and group 3 received 40 mg of the PGE1 analogue misoprostol dissolved in 1 mL normal saline administered by orogastric tube once daily. After 7 days, laparotomy and collection of samples for laboratory analyses were performed, including bacteriological analysis of intestine, mesenteric lymph nodes (MLNs), and blood, and histopathologic examination of intestinal mucosa to determine mucosal thickness and structural damage. Serum bilirubin and alkaline phosphatase levels confirmed OJ in all animals with CBD transection. The mucosal damage score was significantly reduced in jaundiced animals receiving PGE1 compared to jaundiced controls (2.15 +/- 0.74 vs 5.3 +/- 0.59; p < .00001) and mucosal thickness was greater (607 +/- 59.1 microm vs. 393 +/- 40.3 microm; p < .00001). The incidence of BT to MLNs decreased from 90% to 30% (p < .02) when jaundiced rats received PGE1. PGE1 treatment reduced the detection rate of viable enteric bacteria in the blood from 60% to 10% (p < .057). We conclude that administration of PGE1 provides protection against OJ-induced atrophy and damage of intestinal mucosa, and thereby prevents translocation of enteric bacteria to underlying tissues.

Alkaline Phosphatase↗

[A case of umbilical polyp with aberrant pancreas and small intestinal mucosa--analysis of cases of umbilical polyp reported in Japan].

We report a case of a 60 year-old man with an umbilical polyp composed of the aberrant pancreas and small intestinal mucosa. This is an extremely rare lesion which originates in remnants of omphalomesenteric duct and is usually diagnosed in the infant period. Microscopic examination disclosed the aberrant pancreas with exocrine glands and ducts, but no islets of Langerhans. The above findings suggested that the pancreas might have been HEINRICH II in type.

Abdominal Neoplasms↗