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Solubilization of 1,25-dihydroxyvitamin D3 receptor with pyridoxal 5'-phosphate from hen intestinal mucosa.

1,25-Dihydroxyvitamin D3(1,25-(OH)2D3) receptor was solubilized in cytosol fractions upon homogenization of hen intestinal mucosa with pyridoxal 5'-phosphate contained in a low ionic strength buffer. Pyridoxal 5'-phosphate did not inhibit the binding of 1,25-(OH)2D3 to its receptor. The receptor solubilized with pyridoxal 5'-phosphate was similar to the KCl-solubilized receptor in its binding affinity to the hormone and sedimentation coefficient. A majority (greater than 90%) of the mucosal 1,25-(OH)2D3 receptors were obtained as associating with crude chromatin which was prepared with a low ionic strength buffer, and this fraction of the receptor was solubilized with pyridoxal 5'-phosphate. Ten millimolar pyridoxal 5'-phosphate was as effective as approx 0.2 M KCl in solubilizing the receptor from the crude chromatin. Pyridoxal 5'-phosphate also showed a potency to dissociate the 1,25-(OH)2D3-receptor complex previously bound to DNA-cellulose. Pyridoxal 5'-phosphate-related compounds such as pyridoxamine 5'-phosphate and pyridoxal did not show this potency. These results suggest that pyridoxal 5'-phosphate reduced the interaction of 1,25-(OH)2D3 receptor with its nuclear binding components without inhibiting the binding of the receptor to the hormone.

Animals↗

Quercetin-4'-glucoside is more potent than quercetin-3-glucoside in protection of rat intestinal mucosa homogenates against iron ion-induced lipid peroxidation.

Quercetin is a typical antioxidative flavonoid found in vegetables, which is more commonly present as its glucosides, quercetin-3-glucoside (Q3G) and quercetin-4'-glucoside (Q4'G). The main aim of this study was to estimate the antioxidant activity of Q3G and Q4'G on iron ion-driven lipid peroxidation of the gastrointestinal mucosa. Q4'G markedly suppressed the lipid peroxidation when rat gastrointestinal mucosa homogenates were incubated with Fe(NO3)3 and ascorbic acid. Its effectiveness was greater as compared to that of Q3G and comparable to that of quercetin aglycone. Furthermore, Q4'G yielded higher amounts of quercetin aglycone than Q3G on incubation with the homogenates. However, Q4'G showed a lower chelating activity in comparison to Q3G. These results indicate that Q4'G, even though it has a low chelating activity, because of its efficient conversion to antioxidative aglycone on exposure to the mucosa, can act as a powerful antioxidant on iron ion driven lipid peroxidation in the intestinal mucosa. Thus, vegetables rich in Q4'G, such as onion, are likely to serve as favorable antioxidant sources for suppressing iron-induced oxidative stress in the intestinal tract.

Animals↗

The effect of CdCl2 on the respiration of rat small intestine mucosa.

Process of oxygen consumption of rat small intestine have already been studied at the level of whole intestinal wall or mucosa only by means of manometric or polarographic methods. The influence of cadmium on mucosal respiration of three sections of rat small intestine was determined because of its toxicological importance. Oxygen consumption was measured polarographically with Clark electrode at 38 degrees C in Krebs Ringer phosphate medium with 0.011 mol/l glucose. Control as well as cadmium affected respiration values were measured one after the other on the same mucosa. High cadmium concentration (applied as CdCl2) that is 2.2 and 1.4 . 10(-2) mol/l significantly inhibited the respiration in duodenum, jejunum and ileum. Observed inhibition of 80 and 50% on the average approximately for these two concentrations was related (similarly as following effects) to 100% value of control respiration. Concentrations 7.8 and 4.5. 10(-3) mol/l caused mostly lower inhibition of oxygen consumption (with the exception of significant 53% inhibition of jejunal respiration for 7.8. 10(-3) mol/l CdCl2). Low concentrations 10(-4) - 10(-6) mol/l CdCl2 had either no effect or stimulated oxygen uptake in intestinal mucosa. In older rats (weight 300-350 g) the respiration of duodenal and jejunal mucosa was inhibited with cadmium chloride concentration of 10(-6) mol/l.

Animals↗

Intraepithelial leukocytes of the intestinal mucosa in normal man and in Whipple's disease: a light- and electron-microscopic study.

Intraepithelial lymphocytes (IEL) of the intestinal mucosa of normal man and of patients with Whipple's disease were studied by light microscopy of 1-micron-thick sections, and by electron microscopy of thin sections. IEL in normal human intestine tend to be elongated in outline, have few cytoplasmic organelles, have compact nuclei, and are unattached to epithelial cells. IEL in Whipple's disease are more likely to be activated in appearance, ie, to be larger and to contain more cytoplasmic organelles than IEL of normal intestine. The number of IEL/100 intestinal epithelial cells is similar in normal man and in patients with Whipple's disease. Other intraepithelial (IE) cells found in normal intestine include eosinophils and mast cells, and we note for the first time the presence of IE macrophages. There are no "globule leukocytes" in the intestine of normal man or of patients with Whipple's disease. Other IE cells found in the intestine in Whipple's disease include eosinophils, polymorphonuclear (PMN) leukocytes, and macrophages in untreated disease and intraepithelial macrophages in treated disease. These IE cells may be involved in the acute and chronic immune responses of the intestine.

Duodenum↗

Small bowel transit time and roentgenological changes of the intestinal mucosa after jejunoileostomy in obese patients.

In ten patients, operated jejunoileostomy and ileocolostmy because of longstanding obesity resistant to conventional therapy, roentgenological examinations of the small bowel were performed before and after the operation. Seven patients were examined preoperatively, and all were investigated at least twice during a period from 1 to 38 months postoperatively. Preoperatively, the passage time pylorus-cecum was 80-270 min, and postoperatively, it varied between 1 and 30 min. There was no tendency to slowing of the gastrointestinal passage with time. Immediately postoperatively, the patients had 6 to 12 loose stools daily. At investigations performed 6-38 months after the operation, the stool frequency had diminished to 1-4 a day, and the patients had lost 21 to 98 kg in weight. Roentgenologically, an increased thickness of the mucosal folds of the small bowel could be demonstrated in 9 of the 10 patients. The results suggest that in patients with jejunoileostomy, the gastrointestinal passage time is decreased. The bowel function tends to normalize with time, but the passage time remains shorter than normal. Compensatory changes in the intestinal mucosa occur.

Adult↗

[Activation of the processes of lipid peroxidation in the small-intestinal mucosa and liver in peritonitis and possible ways of their correction by a complex infusion-detoxification therapy].

Possibilities of lipid peroxidation (LPO) correction by infusion-detoxication therapy in peritonitis were studied in an experiment on 160 white rats and during clinical treatment of 88 patients with general peritonitis. It was shown that peritonitis development in rats was attended by an increase of LPO products--malonic dialdehyde and diene conjugates, in the hepatic tissue and small intestine mucosa, while the activity of antioxidant defense elements--superoxide dismutase and fat-soluble antioxidants, decreased. It was noted that LPO became normal after intravenous administration of exogenous superoxide dismutase (6 mg/kg) and the blood substitute Mafusol containing Krebs cycle substrate--sodium fumarate (9 ml/kg). Inclusion of Mafusol into the combined therapy of patients with general peritonitis contributed to the reduction of malonic dialdehyde and diene conjugate levels in the blood, normalization of its acid-base state, diminution of medium mass molecule content. Similar normalization of LPO was not recorded when lactosol was used. It has been concluded that blood substitute Mafusol used in the combined therapy of patients with general peritonitis significantly raises the treatment effectiveness.

Animals↗

To make a new intestinal mucosa.

A number of clinical conditions are caused by disorders affecting the mucosal lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal surface area due to congenital defects or due to surgical resections ("short bowel syndrome"). Other patients have inborn or acquired defects of certain mucosal functions (e.g., glucose-galactose malabsorption, bile acid malabsorption). Many patients with these mucosal disorders could be more effectively treated if healthy mucosa were available in larger quantities as a replacement or functional supplement. We therefore developed methods to transplant mucosal stem cells from one part of the intestine to another and to make bioengineered intestinal mucosa. We generated an animal model of bile acid malabsorption using rats that underwent resection of the distal 25% of their small intestine (ileum). This resulted in significant losses of bile acids with the fecal excretions in these animals. We subsequently harvested ileal stem cell clusters from neonatal donors, removed the mucosa from a segment of proximal intestine (jejunum), and implanted the stem cell clusters into the debrided segment of jejunum. After four weeks, the animals had developed a functional "neomucosa." We inserted the "neo-ileal" segment into continuity as a substitute ileum. Postoperative measurements of fecal bile acid excretion showed that we were able to reverse the malabsorption syndrome in this model. This was the first reported neo-mucosa-based treatment of a malabsorption syndrome in vivo. We subsequently studied different biodegradable PGA and PLLA scaffoldings to generate bioengineered intestinal mucosa. We implanted these materials into omentum of rats and were able to identify a PGA/PLLA hybrid material on which engraftment rates of 36% of the available surface area could be achieved. Most recently, we developed a novel technique that permits direct observation of cell-biomaterial interactions after implantation into omentum or intestine in vivo. This method will help to optimize engraftment conditions for stem cell clusters on biomaterials.

Animals↗

Effects of Echinostoma caproni infections on metallic ions in the intestinal mucosa of ICR mice.

Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to study metallic ions in the intestinal mucosa of ICR mice infected with Echinostoma caproni and the mucosa of uninfected control mice. Infected mucosa (n = 9 with about 100 mg wet weight per sample) were examined at 2 weeks p.i. in mice that were infected with about 25 worms per host. Uninfected mucosa (n = 9 with about 100 mg wet weight per sample) were examined in the same time frame as the infected mucosa. Five metals were measured in the mucosa by ICP-AES analysis, as follows: calcium, potassium, magnesium, sodium and zinc. There were no significant differences (Student's t-test, P > 0.05) in the concentrations of calcium, potassium or zinc in infected versus uninfected mucosa. The concentration of sodium was significantly greater (P < 0.05) in the mucosa of infected versus uninfected mucosa, but the situation was reversed in regard to magnesium.

Animals↗

Ion transport across the isolated intestinal mucosa of the winter flounder, Pseudopleuronectes americans: II. effects of cyclic AMP.

Addition of cyclic AMP and theophylline to the intestinal mucosa of the winter flounder, Pseudopleuronectes americanus decreased short-circuit current and net Na and Cl absorption and increased total conductance and the serosa-to-mucosa unidirectional Cl flux (JsmCl). The last two changes were independent of the original rate of NaCl absorption and persisted even when net absorption of Na and Cl had been abolished by ouabain. Voltage clamp experiments revealed that the increment in JsmCl produced by cyclic AMP is PD-insensitive and therefore not due to an increase in the Cl conductance of the paracellular shunt. Cyclic AMP appears, therefore, both to inhibit net NaCl absorption and to increase the Cl permeability and total conductance of the intestinal epithelial cells; its failure to stimulate secretion (in contrast to its action on mammalian intestine) may be related to the absence of crypts in flounder intestinal epithelium.

Animals↗

Effect of reserpine on the 5-hydroxytryptamine and adenosinetriphosphate of the dog intestinal mucosa.

Homogenates were prepared of the mucous membrane of the small intestine from dogs previously treated with high doses of reserpine. The granular material sedimented from these homogenates was centrifuged over a density gradient. The dense fraction usually rich in adenosinetriphosphate and 5-hydroxytryptamine contained little amine and no nucleotide; on the other hand, the less dense material, believed to consist mainly of mitochondria, contained amounts of adenosinetriphosphate similar to those found in animals not treated with reserpine.

Adenine Nucleotides↗

Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.

The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea.

Animals↗

The effect of step-down heating on mouse small intestinal mucosa.

Step-down heating (SDH) was investigated in mouse small intestine by giving a primary (conditioning) treatment at or above 43 degrees C followed by a test treatment below 43 degrees C. Crypt dose-response curves following SDH were compared with those obtained using the test treatment alone; the SDH effect was characterized by a reduction in shoulder (an additive effect) and an increase in slope (thermosensitization). The thermosensitization ratio, defined as slope SDH-heated/slope single-heated, was independent of the conditioning temperature but increased to a maximum of approximately three as the duration of conditioning increased. Thermosensitization was eliminated when the conditioning treatment was itself sufficient to cause significant crypt loss and, also, when the interval between the two treatments was 0.5 h or longer. This period was less than that required for either recovery of the 'shoulder' on the crypt dose-response curve or the development of thermotolerance following the primary treatment. Thermotolerance which develops in intestine during prolonged hyperthermia (after approximately 100 min) was not affected by SDH and Arrhenius analysis indicated that the activation energy for temperatures below 43 degrees C was not significantly altered by SDH. In summary, the SDH effect on small intestine, assessed using the crypt loss endpoint, was similar to thermosensitization observed in vitro. However, the lower magnitude of the effect and its complex dependence on the primary heat treatment suggest either that crypt cells respond to SDH in a unique and characteristic manner or that the crypt assay in vivo and reproductive survival in vitro do not reflect the same endpoint.

Adaptation, Physiological↗

[Properties of Na+/HCO3-(Cl-)-stimulated ATPase in rabbit small intestinal mucosa].

It has been demonstrated that histamine induces in rabbit small intestine an ATPase activity which is stimulated by NaCl or NaHCO3. The Na+/HCO3- (C1-)-stimulated ATPase activity, unlike the Mg2+,HCO3(-)-ATPase activity, has a pH optimum at pH 6.2, is inhibited by ethacrynic acid (10(-4) M) and bivalent metal ions (but not 10(-2) M thiocyanate). The substrate specificity of Na+/HCO3- (C1-)-ATPase and its regulation by Ca2+ ions has been studied. The feasible role of the enzyme in secretion is discussed.

Adenosine Triphosphatases↗

Heparan sulphates from porcine intestinal mucosa. Preparation and physicochemical properties.

A series of fractions of heparan sulphate has been prepared from the glycosaminoglycuronans of porcine intestinal mucosa, in order to relate their physicochemical properties with their biochemical and biological activities. They fall into three classes which may be distinguished by differences in molecular weight distribution and in extent of sulphation. For heterogeneous polymers such as heparan sulphates purification and fractionation must be regarded as interchangeable terms, and some preparative procedures appear to have rather specific effects on the properties of samples isolated by their use. Such considerations apply particularly in the undemarcated boundary region between heparan sulphates and heparin, a region which includes certain 'high activity' heparin fractions of current biological and clinical interest.

Animals↗

Effects of pancreatic duct ligation on the hamster intestinal mucosa. Histological findings.

After pancreatic duct ligation good correlations were observed between degenerative signs of the exocrine pancreas and ultrastructural changes of intestinal epithelial cells: hypertrophy of Paneth and goblet cells; hyperplasia of Paneth cells, mucous cells and 'intermediate granular cells' after the 10th day. On the 7th day, the absorbing area of the intestine (villi area and microvilli area) decrease significantly. These cytological changes partially disappear after the 15th day concomitant to a partial regeneration of the exocrine pancreas. These findings suggest correlations between the epithelial cells of the small intestine and exocrine pancreatic secretion. Different possibilities (direct action of the pancreatic juice or indirect mechanisms) are discussed and proposed to explain the morphological variations of the intestinal mucosa after pancreatic duct ligation.

Animals↗

[Changes in the small intestine mucosa in chronic alcoholism].

Morphologic and enzyme induction phenomena changes in the small bowel mucosa produced by excessive alcohol intake were studied. Both aspects may have nutritional repercussions in alcoholic patients. Three groups of patients were included in the study: group I made up of 20 healthy controls, group II with 30 alcoholic patients with active alcohol intake at the time of the study and group III made up of 30 alcoholics following abstinence. The nutritional status, possible existence of associated liver disease, intestinal morphology and the mucosal and serum gamma glutamyltranspeptidase (GGT) levels were evaluated. The morphologic changes observed under the study conditions, with normal levels of ingestion in alcoholic with active alcohol intake, were mild and could be related with the nutritional status and folate deficiency which some presented than being secondary to a direct toxic effect of the alcohol. Moreover, significant increases were observed in the GGT in the intestinal mucosa of alcoholics with active intake (3.97 +/- 1.37 mU/g of tissue) with respect to the control group (1.86 +/- 0.7 mU/g). The changes were rapidly reversible following abstinence and correlated with the changes observed in serum, thus suggesting an enzymatic induction mechanism.

Adult↗