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At least 1,099 records · Page 61Linked to original sources

Intestinal safety of water-soluble beta-cyclodextrins in paediatric oral solutions of spironolactone: effects on human intestinal epithelial Caco-2 cells.

Effects of water-soluble beta-cyclodextrins (beta CDs) on intestinal epithelial integrity were investigated, to establish the safe use of these beta CDs as solubilizers of spironolactone in paediatric enteral solutions. Mannitol permeability and transepithelial resistance (TER) of human intestinal epithelial Caco-2 cell monolayers during exposure to dimethyl-beta-cyclodextrin (DM beta CD), hydroxypropyl-beta-cyclodextrin (HP beta CD) and sulphobutyl ether beta-cyclodextrin (SBE beta CD) were followed. Staining methods were used to discern cells with damaged membranes and to study the integrity of cytoskeletal actin and tight junctions. Cytotoxicity of the beta CDs was tested by effects on intracellular dehydrogenase activity. Exposure to HP beta CD and SBE beta CD solutions had only minor effects on the integrity of Caco-2 cell monolayers. In contrast, DM beta CD clearly increased the epithelial permeability for the hydrophilic marker [14C]mannitol across Caco-2 monolayers, decreased TER and showed a dose-dependent cytotoxicity. According to staining, DM beta CD increased the permeability of the apical cell membrane without discernable effects on cytoskeletal actin. HP beta CD and SBE beta CD appear to be safe additives for use in enteral spironolactone preparations with respect to their acute local effects on epithelial integrity.

Administration, Oral↗

Stress and glucocorticoid inhibit apical GLUT2-trafficking and intestinal glucose absorption in rat small intestine.

We have proposed a new model of rat intestinal sugar absorption in which high glucose concentrations promote rapid insertion of GLUT2 into the apical membrane, so that absorptive capacity is precisely regulated to match dietary intake. Construction and building work during expansion and refurbishment of our department permitted opportunistic experiments on the effects of building-induced stress on the GLUT2 component of absorption. In fed rats perfused with 75 mM glucose in vivo, stress rapidly inhibited glucose absorption 36.4 +/- 3.0% compared with control rats. Selective inhibition of the GLUT2 component with phloretin demonstrated that stress inhibited the GLUT2 component by 42.8 +/- 3.8%, which correlated with a corresponding diminution in apical GLUT2 levels: the SGLT1 component and its level were unaltered by stress. Effects of stress were reversed by the administration in drinking water of metyrapone, which inhibits 11-beta-hydroxylase. Injection of dexamethasone into control rats 60 min before perfusion resulted in absorption and transporter properties indistinguishable from stressed rats. Our data are consistent with the view that stress activates the hypothalamus-pituitary-adrenal (HPA) axis, causing release of glucocorticoid. The ensuing inhibition of GLUT2 trafficking and absorption seems necessary to prevent enhanced intestinal delivery of glucose to the circulation from antagonizing the essential stress response of glucorticoid in mobilizing peripheral energy stores for emergency purposes.

Animals↗

Certain canine weakly beta-hemolytic intestinal spirochetes are phenotypically and genotypically related to spirochetes associated with human and porcine intestinal spirochetosis.

Four canine weakly beta-hemolytic intestinal spirochetes associated with intestinal spirochetosis (IS-associated WBHIS) were compared with IS-associated human and porcine WBHIS and the type species for Serpulina hyodysenteriae and S. innocens by using phenotypic and genotypic parameters. The IS-associated canine, human, and porcine WBHIS belonged to a phyletic group distinct from but related to previously described Serpulina type species.

Animals↗

Distal intestinal obstruction syndrome in cystic fibrosis treated by oral intestinal lavage, and a case of recurrent obstruction despite normal pancreatic function.

An oral intestinal lavage solution has been successfully used in the treatment of six patients with chronic distal intestinal obstruction syndrome (previously referred to as meconium ileus equivalent) complicating cystic fibrosis and a further case of recurrent small bowel obstruction. The patient with recurrent obstruction is unusual in having no evidence of pancreatic maldigestion, which previously has been considered a prerequisite for the syndrome.

Acute Disease↗

Myoelectric effects of vasoactive intestinal peptide on rabbit small intestine.

Myoelectric recording techniques were used to study the motility of rabbit ileum during infusions of vasoactive intestinal peptide (VIP). VIP was infused intravenously at a rate of 300 pmol X kg-1 X h-1, and peripheral venous blood samples were obtained hourly for VIP assay. VIP was also infused intraluminally at a similar rate, and hourly portal vein blood samples were obtained for VIP assay. Alterations in motility were observed after both intravenous and intraluminal infusions of VIP. These alterations in motility consisted of the migrating action potential complex and repetitive bursts of action potentials. The VIP infusion rate used and the mean peripheral plasma VIP level of 267 +/- 29 pg/ml attained during intravenous VIP infusion were similar to those that induced intestinal secretion in other animal species. Portal venous VIP levels (93 +/- 21 pg/ml) were unchanged during the intraluminal infusion of VIP. These studies show that intravenous infusion of VIP causes alterations in motility of rabbit ileum. These alterations in motility with concomitant secretion of water and electrolytes may contribute to the diarrhea induced by VIP infusion. In addition, intraluminal infusion of VIP also induced alterations in myoelectric activity, which suggested that this peptide has a luminal effect as well as a hormonal effect.

Action Potentials↗

Effects of porcine intestinal heptacosapeptide and vasoactive intestinal polypeptide on insulin and glucagon secretion in rats.

Pure porcine vasoactive intestinal polypeptide (VIP) and porcine intestinal heptacosapeptide (PHI) were infused in fed rats in doses of 1, 10, and 100 pmol/kg . min. The peptides were administered alone or together with glucose (40 mg/kg . min) or arginine (50 mg/kg . min). In the basal state, VIP at a dose of 1 pmol/kg . min and PHI at a dose of 10 pmol/kg . min produced a slight but significant hypoglycemia, whereas 100 pmol/kg . min VIP and PHI had a hyperglycemic effect. VIP at a dose of 10 and 100 pmol/kg . min enhanced the glucose-induced secretion of insulin. PHI exerted such an effect only when administered at the highest dose. When arginine was present as a secretagogue, 10 pmol/kg . min of both VIP and PHI potentiated secretion of insulin and glucagon and elevated the prevailing hyperglycemia. In conclusion, when given as a constant infusion in rats, both PHI and VIP exert a direct hypoglycemic effect and modulate the influence of glucose and arginine on insulin and glucagon secretion. It is as yet unclear to what extent these findings reflect normal physiological events.

Animals↗

Partial reconstruction of intestinal continuity in the treatment of severe side effects following intestinal shunt operation for obesity.

Severe side effects of intestinal shunt operation were the indication for reoperation of eight patients. To maintain the acquired weight loss, complete revision of the bypass and return to normal gastrointestinal continuity was omitted. The shunt was taken down and moved 20 cm in proximal direction on the terminal ileum. After this procedure weight loss was converted to a small gain in weight, diarrhoea decreased, and electrolyte disturbances turned out to be a minor problem. At the same time quality of life improved. We suggest that this type of reoperation is adequate in most patients suffering from severe side effects after intestinal bypass operation.

Adult↗

Small intestinal growth regulatory factors extracted by simple diffusion from intact irradiated intestine and tested in vivo.

Following a dose of 8 Gy of gamma-rays delivered to the entire body of BDF1 mice, the proliferative activity in the crypts of the small intestine changes. The labelling and mitotic activity both fall precipitously, but in the lower regions of the crypt recovery from this fall begins soon after irradiation with cyclic fluctuations. Forty-five to fifty hours after irradiation, control levels are reached after which there is an overshoot. The number of clonogenic cells in the crypt shows a somewhat similar pattern of regeneration and overshoot. It has been assumed that these changes reflect the production of endogenous signals for proliferation and inhibition and these might be extracted by diffusion through the gut wall. We report here that at appropriate times after irradiation stimulatory and inhibitory extracts could be prepared. Appropriate in vivo assay techniques have been developed for testing inhibitors or stimulators making similar use of the patterns of proliferative regeneration after irradiation. Extracts prepared at either 15 h or 39 h after irradiation, i.e. during the phase of active regeneration are quite potently stimulatory on recipient animals 96 h after irradiation (i.e., following the decline from a proliferative overshoot) when injected twice 3 h apart. Extract prepared 72 h after irradiation (shortly after the overshoot peak) is strongly inhibitory when tested on unirradiated animals, or animals 90 h after irradiation, when injected four times 2 h apart. An accompanying paper shows that the stimulatory extract is powerfully active on intestinal cell lines. The in vitro approach is currently being used to characterise the stimulatory factor.

Animals↗

Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells.

Mucosal damage induces a massive influx of serum complement components into the lumen. The epithelium produces a number of factors that can potentially ameliorate injury including intestinal trefoil factor (ITF), a small protease-resistant peptide produced and secreted onto the mucosal surface by goblet cells, and decay-accelerating factor (DAF), a protein produced by columnar epithelium which protects the host tissue from autologous complement injury. However, coordination of these intrinsic defensive products has not been delineated. DAF protein and mRNA expression were evaluated by immunoblotting and Northern blotting, respectively. NF-kappaB-DNA binding activity and DAF promoter activity were assessed by an electrophoretic gel mobility shift assay and a reporter gene luciferase assay, respectively. ITF induced a dose- and time-dependent increase in DAF protein and mRNA expression in human (HT-29 and T84) and rat (IEC-6) intestinal epithelial cells. In differentiated T84 cells grown on cell culture inserts, basolateral stimulation with ITF strongly enhanced DAF expression, but apical stimulation had no effects. The C3 deposition induced by complement activation was significantly blocked by the treatment with ITF. In HT-29 cells, ITF increased the stability of DAF mRNA. ITF also enhanced the promoter activity of the DAF gene via NF-kappaB motif and induced activation of NF-kappaB-DNA binding activity. ITF promotes protection of epithelial cells from complement activation via up-regulation of DAF expression, contributing to a robust mucosal defense.

Animals↗

Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor.

In rodents, fibroblasts (FBs) mediate stem cell factor (SCF)-dependent growth of mast cells (MCs). In humans, SCF is mandatory for MC differentiation and survival. Other factors such as IL-3, IL-4, and nerve growth factor (NGF) act in synergism with SCF, thus enhancing proliferation and/or preventing apoptosis in MCs. In this study, we studied in vitro interactions between human MCs and human FBs, both isolated from the intestine and purified to homogeneity. In coculture with FBs, MCs survived for up to 3 wk, whereas purified MCs cultured alone died within a few days. TNF-alpha and IL-1beta, which both did not affect MC survival directly, enhanced FB-dependent MC growth. We provide evidence that FB-derived MC growth factors are soluble, heat-sensitive molecules which down-regulate MC apoptosis without enhancing MC proliferation. However, only low amounts of SCF were measured in FB-conditioned medium (<0.2 ng/ml). Moreover, blocking of SCF/c-kit interaction by anti-SCF or anti-c-kit Abs and neutralization of IL-3, IL-4, and NGF did not affect MC survival in the coculture system. In conclusion, our data indicate that human FBs promote survival of human MCs by mechanisms independent of SCF, IL-3, IL-4, and NGF. Such interactions between MCs and FBs may explain why MCs accumulate at sites of inflammatory bowel disease and intestinal fibrosis.

Apoptosis↗

[Familial syndrome combining short small intestine, intestinal malrotation, pyloric hypertrophy and brain malformation. 3 anatomoclinical case reports].

Anatomoclinical study of 3 cases of an exceptional malformative condition characterized by: --extreme shortness of the small intestine, --mesenterium commune, --hypertrophic pylorus, --malformation of the central nervous system (heterotopia, absence of operculum temporale). Clinically this malformative condition is characterized by failure and inertia of the intestinal peristalsis producing at intervals of 10-15 days episodes of subocclusion, the repetition of which causes death. The syndrome is familial and seems to be of autosomal recessive inheritance. The absence of mechanical obstruction, the repeated failure of colostomy and ileostomy, the normal aspect of the myenteric plexuses verified by cytoenzymatic and silver stains allow to individualize this anatomoclinical syndrome and to rule out the hypothesis of Hirschsprung's disease, Chagas' disease, idiopathic megacolon or hypoplasia of the myenteric plexuses. The association of cerebral malformations leads to consider the responsibility of a lack of synthesis of a same specific intermediate factor which is up to now poorly determined, implicated in the neuronal migration and neuromuscular transmission.

Abnormalities, Multiple↗

[Small intestine intubation for treatment of patients with peritonitis and intestinal obstruction].

The analysis of 36 case records of patients with peritonitis (n = 12) and intestinal obstruction (n = 24) is presented. Nasogastrointestinal intubation of the small bowel was used in combined treatment. The aims, indications and contraindications for the intubation are formulated. Bacteriologic and biochemical parameters of bowel content were studied. It was established that the quantity of enterobacteria and unfermenting gram-negative bacteria was increased in intestinal paresis, the alkaline phosphatase, amylase, bilirubin, transaminase, a potassium content were increased as well. For the tube to function from the first hours after its introduction it should be periodically properly washed with sodium hypochlorite in concentration 300 mg/l.

Female↗

Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice.

This study was conducted to confirm the hypothesis that intestinal microflora are required for the development of adenocarcinoma in the colon of the TCRbeta and p53 double-knockout (TCRbeta-/- p53-/-) mouse. Germ-free TCRbeta-/- p53-/- mice were produced. At 7 weeks of age, the animals were divided into two groups (n = 10/group), and one of these groups was conventionalized. Animals of both groups were subjected to histopathological examination for adenocarcinoma of the colon at 4 months of age. There was no development of adenocarcinoma of the colon among the germ-free mice, whereas in the conventionalized group, adenocarcinomas of the ileocecum and cecum were detected in 70% of animals. These results indicate the usefulness of the TCRbeta-/- p53-/- mouse as a colon cancer animal model that develops spontaneous adenocarcinoma of the colon early in life, and suggest that intestinal microflora play a major role in the development of adenocarcinoma of the colon in this animal model.

Adenocarcinoma↗

[Intestinal microbiocenosis in children with intestinal enzymopathy].

141 children with different kinds of intestinal enzymopathy were examined; of these, 33 had celiac disease, 39--the syndrome of celiac disease, 12--congenital lactase deficiency and 57--the syndrome of disaccharidase insufficiency. In these patients a significant decrease in the average characteristics of the main protective flora and the growth of hemolytic and lactose-negative enterobacteria were established. In all groups of patients increased amounts of Proteus were detected, which was indicative of profound dysbiosis. The content of bifidobacteria was found to be decreased in 89.5-97% of the patients and the content of lactic acid bacteria, in 15.8-33.3%. The decreased content of Escherichia coli with normal enzymatic activity (less than 10(7) colony-forming units) was noted in one-third of the patients with the syndrome of celiac disease and congenital lactase deficiency, in about a half of the patients with the syndrome of disaccharidase insufficiency and least of all in patients with celiac disease (9.1%). The association of opportunistic microbes was detected in 15.6% of the patients, more often in those with celiac disease, the syndrome of celiac disease and congenital lactase deficiency. The severity of disturbances in intestinal eubiosis was found to depend on the gravity of the patients' state.

Celiac Disease↗

[Changes in blood pressure and impulse activity in intestinal nerves during exposure of small intestine interoreceptors to lactic acid].

I. a. administration of threshold concentration (0.2 ml 7.8 mM) of lactic acid into the small intestine was found to increase afferent and efferent impulsation in the intestinal nerves as well as the systemic arterial blood pressure in anesthetized cats. Increase in the lactic acid concentration up to 250 mM/l resulted in two-phasic augmentation of the nerve responses and of the pressor reflexes. In the range from 7.8 to 62.5 mM/l of lactic acid concentration the absolute magnitude of pressor reflexes was 2.3 +/- 0.6--4.2 +/- 0.5 mm Hg. Further increase in the lactic acid concentration (up to 250 mM/l) produced on augmentation in the reflexes magnitude up to 18 +/- 2.8 mm Hg. A possible functional role of afferent impulses generated by the tissue receptors following an increase in metabolites concentration in the organs, is discussed.

Animals↗