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Light and electron microscope study on developing intestinal mucosa in rat fetuses with special reference to the obliteration of the intestinal lumen.

The development of the small intestine in rat fetuses was studied by light and electron microscopy with special reference to morphological events during the stage of obliteration. Prior to this stage, the epithelium lining the intestinal lumen was simple, tall and columnar and consisted of undifferentiated cells mutually joined by the adluminal junctional complex. At the stage of obliteration, the epithelium appeared stratified and the intestinal lumen was identified as a narrow irregular slit. In addition to the junctional complex surrounding the intestinal lumen, secondary junctional complexes were scattered in the more basal parts of the epithelium. The intra-epithelial cavity was formed within the macula occludens of the secondary junctional complex and became larger by division of the surrounding cells. Since the small intestinal epithelium was essentially simple columnar, mitosis occurred facing the lumen. At the stage of obliteration when the number of epithelial cells was rapidly increasing, mitosis occurred facing not only the main intestinal lumen but also the intra-epithelial cavity. As the intra-epithelial cavities fused with the main intestinal lumen, mesenchyme invaded to form villi and the epithelium returned to a simple columnar form. Consequently, the intestinal lumen was enlarged and villi were formed. At the same time, absorptive cells with a brush border appeared in the villous epithelium and immature goblet cells were occasionally seen.

Animals↗

Alkaline phosphatase from calf intestinal mucosa in reversed micelle systems: modulation of enzyme membrane activity by pH variation.

The effect of pH variation in aqueous microphases of Aerosol OT (AOT, sodium bis(2-ethylhexyl)sulfosuccinate)/water/octane and brij 96 (oleyl poly(10)oxyethylene ether)/water/cyclohexane reversed micelle (RM) systems on the membrane activity of alkaline phosphatase (AP) from calf intestinal mucosa (EC 3.1.3.1) has been studied. The dependence of enzyme activity on surfactant concentration is observed only for membrane forms of enzymes, and is absent for water soluble forms. In the case of AP, the manifestation of this dependence was governed by the pH of the aqueous microphase of the RM system: it was not observed at the pH-optimum of the enzymatic reaction (pH 10.0-10.5), but appeared at pH below 9.7 and above 10.5. Such behavior may result from the pH-induced change of the enzyme conformation, which according to the fluorescence spectroscopy data takes place in the vicinity of the pH-optimum. This change is probably accompanied by the exposure/masking of an anchor group providing the AP interaction with the RM matrix.

Alkaline Phosphatase↗

Compactin inhibits cholesterol synthesis in lymphocytes and intestinal mucosa from patients with familial hypercholesterolaemia.

Compactin (2000 nmol/l), a potent competitive inhibitor of the rate-determinign enzyme for cholesterol synthesis (3-hydroxy-3-methyl-glutaryl coenzyme-A reductase), inhibited by about 90% cholesterol synthesis from 14C-acetate in isolated lymphocytes from healthy control and from patients heterozygous for familial hypercholesterolaemia (F.H.). In isolated intestinal mucosa, a physiologically important tissue for cholesterol synthesis, compactin (2000 nmol/l) suppressed cholesterol synthesis by approximately 50% in controls and F.H. patients. Compactin or its derivatives may prove to be useful in the treatment of hypercholesterolaemia.

Acetates↗

A synthetic analog of prostaglandin E(1) prevents the production of reactive oxygen species in the intestinal mucosa of methotrexate-treated rats.

Administration of methotrexate to rats results in severe enterocolitis and death. Previous our studies showed that a synthetic analog of prostaglandin E(1), OP-1206 [17S, 20-dimethyl-trans-Delta(2)-prostaglandin E(1)] ameliorated the anticancer agent-induced enterocolitis of rats. In the current study, we have focused on the biochemical effect of OP-1206 on the methotrexate-induced intestinal inflammation implicating reactive oxygen species (ROS). Methotrexate (15 mg/kg body weight) was orally administered to rats once daily for 5 days. OP-1206 (0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days. On the 6th day, the chemiluminescence from the jejunum was measured to evaluate the generation of ROS. Spontaneous chemiluminescence from the jejunum of the methotrexate-treated rats increased significantly, compared with the control. Luminol-enhanced chemiluminescence from inflamed mucosal scrapings from the jejunum of the methotrexate-treated rats indicated more remarkable enhancement than the control rats. The treatment of OP-1206 with methotrexate showed significantly lower chemiluminescence of both the jejunum and mucosal scrapings than those of the methotrexate-treated rats. The alkaline phosphatase (ALP) activity, as a marker of small intestinal differentiation, in the intestinal mucosa of the methotrexate-treated rats decreased remarkably, but that of the methotrexate and OP-1206-treated rats was significantly higher than that of the methotrexate-treated rats. Thus, OP-1206 may possibly help the anticancer chemotherapy by protecting the small intestine from the methotrexate-induced damage.

Alprostadil↗

Properties of the transferrin associated with rat intestinal mucosa.

The transferrin that is isolated from washed intestinal mucosal cell preparations consists partly of a fraction that has properties distinguishing it from serum transferrin. The serum transferrin contaminating mucosal preparations, even when fully saturated with iron and in the presence of proteinase inhibitors, also acquires the properties of the mucosal transferrin when the mucosa is homogenised. The mucosal transferrin is modified by a single cleavage of the polypeptide chain yielding a disulphide-linked peptide of 6550 daltons linked to the parent protein by a disulphide bridge. The amino-terminal sequence of the first 11 residues of this peptide could be aligned with both the known rat and human transferrin carboxy-terminal sequences. In both cases the sequence is preceded by a phenylalanine residue (residue 622 of human transferrin). This suggested that a mucosal chymotryptic enzyme was responsible even though rat transferrin is not susceptible to alpha-chymotrypsin if fully iron-saturated. Since transferrin mRNA is not found in the intestinal mucosa it must be imported from the serum. It remains uncertain whether the modified transferrin is present naturally and plays a role in iron absorption but these findings do indicate the eventual fate of any transferrin imported into an intestinal cell.

Amino Acid Sequence↗

The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa.

In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene. In this paper, the effects of polyamines and their analogues on the sedimentation properties of vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding activity of the receptor, were studied. In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D receptor dose-dependently. These findings show that polyamines can activate vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well. Sucrose density gradient analysis using various kinds of polyamine analogues having various numbers of cations showed that the number of cation of polyamines is important for the efficiency to change the sedimentation coefficient of vitamin D receptor, and that the distance between two cationic charges does not play an important role.

Animals↗

Fixing the intestinal mucosa in the bone marrow transplant patient: lessons from other intestinal immunodeficiencies and inflammatory disorders.

Gastrointestinal inflammation is common following bone marrow transplantation. Key pathogenetic events, such as major histocompatibility complex (MHC) expression on intestinal epithelial cells and local production of cytokines in the gastrointestinal mucosa, are common features of many gastrointestinal inflammatory disorders. Drawing from clinical experience of the treatment of other disorders associated with gastrointestinal inflammation, such as ulcerative colitis and Crohn's disease, a number of therapeutic alternatives may be relevant for the bone marrow transplant patient with significant graft-vs.-host disease (GvHD). Options to consider include therapeutics that alter inflammatory cell migration, anti-inflammatory cytokines, direct neutralization of proinflammatory cytokines, and cytokines that promote epithelial restitution in the gastrointestinal mucosa. In addition, a variety of nutritional and other novel treatments are available, which may improve epithelial function or which have anti-inflammatory actions. Prospective studies of combined nutrient and cytokine-modulating treatments for the bone marrow transplant patient are warranted.

Bone Marrow Transplantation↗

In vivo demonstration of T lymphocyte migration and amelioration of ileitis in intestinal mucosa of SAMP1/Yit mice by the inhibition of MAdCAM-1.

The aetiology of Crohn's disease (CD) remains unknown. Since SAMP1/Yit mice have been reported to develop CD-like spontaneous enteric inflammation, such mice have been studied as an animal model of CD. In this study, using this model we examined T lymphocyte migration in microvessels of intestinal mucosa in vivo and the expression of adhesion molecules by immunohistochemistry. Fluorescence-labelled T lymphocytes isolated from AKR/J (control) mice were injected into the tail veins of recipient mice, and T lymphocyte migration in the postcapillary venules of Peyer's patches, submucosal microvessels, and villus capillaries of the terminal ileum was monitored using an intravital microscope. Adhesion of T lymphocytes was significantly increased in 35 week old SAMP1/Yit mice compared with that in AKR/J or 15 week old SAMP1/Yit mice. Immunohistochemical study showed increased infiltration of CD4, CD8 and beta7-integrin-positive cells and increased expression of MAdCAM-1 and VCAM-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against MAdCAM-1 and VCAM-1 significantly inhibited adhesion of T lymphocytes to microvessels of the terminal ileum, and anti-MAdCAM-1 antibody showed stronger suppressive effect than the anti-VCAM-1 antibody. Periodical administration of anti-MAdCAM-1 antibody twice a week for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice, but submucosal hypertrophy was not significantly suppressed. Anti-VCAM-1 antibody treatment failed to show significant resolution of ileitis. In addition, anti-MAdCAM-1 antibody treatment also attenuated established ileitis. The results demonstrate that, although MAdCAM-1 and VCAM-1 play an important role in T lymphocyte-endothelial cell interactions in SAMP1/Yit mice, MAdCAM-1 may be a more appropriate target for therapeutic modulation of chronic ileitis.

Animals↗

Identification of apamin binding sites in rat intestinal mucosa.

Apamin, a specific blocker of one class of Ca(2+)-activated K+ channes, was used to detect the apamin receptors associated with K+ channels in the mucosa of the rat jejunum and colon. Two receptor sites for 125I-apamin have been identified. These sites differed in their affinity for apamin (jejunum: KD1 = 1.1 nM and KD2 = 170 nM; colon: KD1 = 0.5 nM and KD2 = 1.1 nM and KD2 = 140 nM) and the maximum number of sites (jejunum: B(max1) = 111 and B(max2) = 4030; colon: B(max1) = 187 and B(max2) = 7550 fmol/mg of protein). 125I-apamin binding was stimulated by K+ ions with K0.5 = 1.0 mM and inhibited by the neuromuscular blocker tubocurarine (KI = 50 microM). We interpret these data to demonstrate that the high-affinity, low-capacity binding sites reflect the existence of apamin-sensitive K+ channels in the intestinal mucosa.

Animals↗