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Intestinal absorption of tolfenamic acid at experimental malabsorption states in rats.

Absorption kinetics of 14C-labelled N-(3-chloro-o-tolyl)-anthranilic acid (tolfenamic acid, 14C-TA, Clotam) from the small intestine was studied in intact rats and in rats with malabsorption states provoked by methotrexate, starvation, and triparanol. 14C-TA was administered intravenously and intraduodenally, and the drug concentrations in the blood were followed up radiometrically. A multi-compartmental model was applied for mathematical analysis. Theoretical model parameters were computed, and absorption parameters were then derived from the theoretical ones. The absorption half-life of 14C-TA was 5.3 min in the controls, 10.8 min in the methotrexate-intoxicated, 7.5 min in the fasted, and 5.3 min in the triparanol-intoxicated rats. The absorbed fraction of the intraduodenal 14C-TA dose was 100% in each experimental group as well as in the controls. It is suggested that the slower transfer of 14C-TA through the intestinal barrier in the methotrexate-intoxicated and fasted rats may be caused by the reduction of the absorptive surface.

Animals↗

Mucosal barrier and immune mediators.

The intestinal mucosa functions is an immunologic organ that plays a major role in the development of oral tolerance and host-defense mechanisms. Antigens must cross the intestinal epithelium in a controlled manner to interact with dendritic antigen-presenting cells, because bacteria or their products are a primary risk factor for the development of intestinal inflammation. Therefore, the regulation of the intestinal epithelial cell barrier is central to the development of intestinal immunity and inflammation, but the involved mechanisms are largely unknown. Intestinal barrier function relies on the formation of tight junctions at the apical contact areas of intestinal epithelial cells. Tight junctions have a highly dynamic structure whose permeability, assembly, or disassembly can be regulated by a variety of cellular and metabolic mediators, including cytokines, which have major functions in the immune system. Immune modulators control tight junction dependent intestinal barrier function during development, wound healing, and pathologic processes such as cancer, infection, and chronic inflammation.

Journal Article↗

Mucosal permeability of ileal and colonic reservoirs for urine.

OBJECTIVES: To evaluate the intestinal mucosal permeability in continent reservoirs for urine. PATIENTS AND METHODS: The mucosal permeability in continent urinary reservoirs, constructed either from an ileal or a colonic segment (six patients each), was assessed by analysing serial samples of plasma, after instilling the reservoir with 51Cr-ethylene diaminetetra-acetic acid (51Cr-EDTA), and serum, after instillation with polyethylene glycol (PEG 400). RESULTS: There was no or negligible permeation of 51Cr-EDTA and PEG 400 in either type of reservoir, as there was no significant increase of the markers in plasma and serum, respectively. CONCLUSION: The intestinal barrier to medium-sized hydrophilic molecules seems intact in continent urinary reservoirs. The lack of significant permeation of 51Cr-EDTA confirms the usefulness of a single injection of 51Cr-EDTA for the determination of glomerular filtration rate in patients with intestinal urinary diversion.

Colon↗

Identical intestinal permeability changes in children with different clinical manifestations of cow's milk allergy.

To determine the relationship between clinical symptoms of cow's milk allergy (CMA) and intestinal permeability, 51 children (mean age, 13 months) were studied during a diagnostic milk provocation test. Intestinal permeability was assessed by orally administered lactulose (4 gm) and mannitol (0.8 gm) immediately before (day 0) the milk challenge and 3 days later (day 3). Twenty-four patients evinced cutaneous symptoms and 27, gastrointestinal symptoms. The mean (95% confidence interval) urinary lactulose/mannitol recovery ratios before the milk challenge were, in both groups of patients, comparable to the level of that of control patients, 0.02 (0.01 and 0.03). A rise in lactulose/mannitol excretion ratios followed cow's milk administration by day 3 in patients with skin symptoms, 0.06 (0.03 and 0.13), as well as in patients with gastrointestinal symptoms, 0.08 (0.04, 0.17). These levels were significantly different from the control level, p = 0.003, and the prechallenge level, p = 0.01. This difference was caused by a concomitant increase in urinary recovery of lactulose and a decrease of mannitol. These results indicate that the intestinal barrier is equally altered in patients with different clinical manifestations of CMA and further suggest that enhancement of mucous membrane permeability is not a primary defect in the pathogenesis of CMA but rather a secondary phenomen, possibly caused by a hypersensitivity reaction in the intestinal mucosa.

Administration, Oral↗

Intestinal permeability in humans is increased after radiation therapy.

PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.

Aged↗

[Phospholipid composition of mucous membrane tissue in the gastrointestinal tract of rabbits in simulated Salmonella infections].

The paper deals with the phospholipid composition in the mucosa tissue of different areas of gastrointestinal tract and in membranes of the villous margin of small intestine enterocytes under conditions of experimental salmonellosis infection. A decreased relative content of cardiolipin is observed in all periods of the infection process in the stomach mucosal tissue and in the period of the disease height and convalescence--in the sigmoid colon. Phosphatidyl choline appears in the tissue of duodenum and jejunum during the height of the infection process. An increase in a relative content of lysophosphatidyl choline and phosphatidyl serine and a decrease in that of phosphatidyl ethanolamine are revealed in membranes of enterocyte villous margin when modelling the diarrhea process by the intraperitoneal administration of the lipopolysaccharide complex of salmonellas. The found changes in the composition of phospholipids in the mucous membrane tissue and membranes of the enterocytes villous margin are supposed to reflect alterations in the functional state of the intestine barrier and play a definite role in development of the diarrhea syndrome.

Animals↗

Effects of immunonutrition on intestinal mucosal apoptosis, mucosal atrophy, and bacterial translocation in head injured rats.

BACKGROUND: Immunonutrition has been demonstrated to modulate gut function, reduce infectious complications, hospital stay, and ventilator days in the critical patients. AIM OF THE STUDY: We assessed the effect of immunonutrition for the prevention of intestinal mucosal atrophy, apoptosis, and bacterial translocation in head injured rats. METHODS: Thirty five rats were randomised into 5 groups. Following moderate closed head injury, in Group 1; Standard Enteral Nutrition, Group 2; Immunonutrition, Group 3; TPN, Group 4; pe. saline were applied. Group 5 was control group (chow-fed). The rats were sacrificed and segments of the ileum were removed for histologic examination, and samples of tissues taken for microbiologic evaluation. RESULTS: Both intestinal apoptosis and mucosal atrophy were significantly lower in Group 2 and Group 5 (p<0.008). Bacterial translocation was significantly lower in Group 2 than Group 1 (p<0.008). CONCLUSION: The enteral immunonutrition prevents intestinal barrier function in brain injured rats.

Animals↗

Effect of mesodiencephalic modulation on small intestinal mucosa after massive blood loss in rats.

Effect of mesodiencephalic modulation on small intestinal mucosa was studied in rats subjected to massive blood loss. Massive blood loss induced structural changes in intestinal epitheliocytes typical of tissue hypoxia: intraintestinal edema, mitochondrial alterations, and microcirculation disturbances. A single session of mesodiencephalic stimulation carried out 60 min after massive blood loss produced a pronounced adaptive effect, restored disturbed structure of the intestinal villi, and induced compensatory hypertrophy of the mitochondria. This suggests that mesodiencephalic modulation promotes normalization of intracellular energy metabolism, improves the absorption capacity of bordered enterocytes, and restores the disturbed intestinal barrier.

Adaptation, Physiological↗

[Effect of mold fungus spore consumption with food on systemic anaphylaxis in rats].

An influence was studied in experiment of intragastrically administrated milk cream contaminated with mould fungi spores on systemic anaphylactic reaction gravity in Wistar albino rats sensitized with egg albumin (EA). During 28 days sensitized rats intragastrically received cream containing 10(3) or 10(6) colony forming units of 5 fungal species in one cm3. After being challenged rats developed mild anaphylactic shock followed by elevation of small intestinal permeability for macromolecular tracer polyethylene glycol 4000. An increase of small intestinal permeability was also noticed in unsensitized rats that were fed with cream contaminated with 10(6) spores per cm3. Unexpectedly these effects were not additive: the intestinal permeability in sensitized rats decreased at maximal level of contamination. This may be explained by strengthening of gastrointestinal motility in these animals. Significant elevation of antibody production against EA was revealed in sensitized rats that received cream contaminated by spores at high level. The data obtained signify that milk products fungal contamination that could not be revealed by sense may nevertheless have negative impact on intestinal barrier function and sensitization.

Anaphylaxis↗

[Participation of various bacterial species in translocation in intestines of rats subjected to stress].

In the rats, which were treated with impairing factors such as: malnutrition, cooling down and ischaemia, translocation was studied. Aerobes as well as anaerobes which penetrated beyond the intestine into the mesenterium, liver, spleen and kidneys were sought. Bacteria in peripheral blood were not found. The results show that the type of bacterium undergoing translocation does not depend on the factor impairing "intestinal barrier" and translocation mechanisms are most probably the same for all the bacteria found.

Animals↗

Water-soluble ethylhydroxyethyl cellulose prevents bacterial translocation induced by major liver resection in the rat.

Enteric bacteria might act as pathogens, translocating across the intestinal barrier to extraintestinal sites after major liver resection. In the current study, water-soluble ethylhydroxyethyl cellulose (EHEC) was administered before hepatectomy to evaluate the influence on bacterial translocation induced by major liver resection, phagocytic capacity by visceral and circulating macrophages, enteric bacterial population, and bacterial adherence on the intestinal surface in rats subjected to sham operation or to 70% or 90% hepatectomy. Oral or intravenous (IV) administration of EHEC reduced the incidence of bacterial translocation to mesenteric lymph nodes (MLN) and blood after major liver resection. Oral EHEC appeared more effective than IV administration in protecting against bacterial translocation to MLN in animals with 90% hepatectomy. Ethylhydroxyethyl cellulose (oral and IV) significantly diminished intestinal macrophage uptake capacity of 125I-labeled, heat-killed Escherichia coli as compared with animals without EHEC administration. Overgrowth or colonization of enteric bacteria after major liver resection could be prevented by oral or IV EHEC. Adherence of 14C-labeled, alive E. coli on the intestinal mucosa decreased after EHEC treatment in animals subjected to major liver resection. Systemic arterial pressure and intestinal blood flow markedly decreased from 1 hour and on after 90% hepatectomy. Intravenous administration of EHEC did not improve these alterations. Bacterial hydrophobicity and surface negative charge were significantly reduced 1 hour after bacterial culture with EHEC. Thus, EHEC appears to be a potent agent preventing translocation of enteric bacteria from the gut after major liver resection, by altering the surface characters of enteric bacteria, balancing the enteric microflora, inhibiting bacterial attachment onto the intestinal surface, and blocking phagocytosis by intestinal macrophages.

Animals↗

[Bacterial translocation from the nutritional perspective].

A variety of situations involving loss of the physical integrity of the gastrointestinal barrier, excess intraluminal bacterial growth or immunological compromise of the host, have been shown experimentally to predispose to bacterial translocation. While colonization of the mesenteric ganglia is a mechanism which stimulates local immune defenses, distant colonization of other organs causes these defences to fail. In general, in the latter situation, a variety of factors must combine, notably the nutritional state or nutritional therapy. Protein malnutrition states do not alone generate bacterial translocation, but they do facilitate the distant dissemination of germs in situations such as endotoxemia. Bacterial translocation is objectivized after the prolonged use of total parenteral nutrition or of chemically defined non-fiber diets. The addition of fiber restores the architecture and physiology of the intestinal microvilli and prevents bacterial translocation in animals with a variety of morphological lesions of the intestinal barrier. While the results of the clinical studies are as yet not very conclusive, there is a clear link between bacteremia of intestinal origin and multiple organ failures. Nutritional support of patients with an acute metabolic compromise must, at least as inferred from the experimental studies, take account of the following factors: in the first place, the use of a preparation with a qualitatively and quantitatively suitable fiber content, to prevent atrophy of the intestinal villi; in the second place, the use of "scavenger" agents or physiological sweepers of the free radicals of oxygen, such as vitamin A, E or C or selenium; and, finally, day by day there is an increasing interest in the therapeutic use of substrates with immunomodulatory capacity, such as glutamine or arginine. On the other hand, the use must be questioned of substances such as Omega 3 series polyunsaturated fatty acids which are on their own able to increase lipidic peroxidation induced by free oxygen radicals.

Animal Nutritional Physiological Phenomena↗

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.

Adult↗

Intestinal function and metabolism in the early adaptive phase after massive small bowel resection in the rat.

PURPOSE: The aim of this study was to investigate the early adaptive responses in metabolism and gut function after massive small bowel resection. METHODS: Male Wistar rats underwent an 80% small bowel resection (Ent group, n = 9) or a transection and reanastomozing (Sham group, n = 7). After 24 hours, substrate fluxes across the gut were determined together with intestinal protein synthesis, polyamine concentrations in gut tissue, and gut function by testing intestinal permeability using the urinary recovery of lactulose and rhamnose. To test for the effect of starvation, healthy starved rats were studied. RESULTS: In the Ent group, intestinal uptake of glucose, lactate, glutamine, phenylalanine, branched chain amino acids, and total amino acids were equal to or higher than that in Sham rats. Intestinal protein synthesis increased, accompanied by an increase in spermidine to spermine polyamine ratios in the ileum and in the jejunal muscular layer. The urinary lactulose to rhamnose ratio also increased, suggesting increased intestinal permeability. CONCLUSIONS: 24 hours after massive small bowel resection, adaptive responses in metabolism and gut function already can be observed, as indicated by increased intestinal uptake of substrates and increased protein synthesis. This, however, is accompanied by an increase in intestinal permeability, which may indicate impaired intestinal barrier function. J Pediatr Surg 36:1746-1751.

Adaptation, Physiological↗

Zinc supplementation tightens "leaky gut" in Crohn's disease.

OBJECTIVES: Small intestinal permeability is often increased in patients with Crohn's disease and may be pathogenic for clinical relapses. No effective prophylactic treatment is available for these patients. The aim of this study was to ascertain whether zinc supplementation may improve intestinal permeability. METHODS: We studied 12 patients with quiescent Crohn's disease who had been in remission for at least 3 months and had increased intestinal permeability on two separate occasions within the last 2 months. Patients received oral zinc sulfate supplements (110 mg three times a day) for 8 weeks and were followed-up for 12 months thereafter to monitor relapses. RESULTS: We found that the lactulose/mannitol ratio was significantly higher before supplementation than after (0.041 +/- 0.003 versus 0.026 +/- 0.005). During follow-up, 10 patients had normal intestinal permeability and did not relapse; of the remaining two who had increased intestinal permeability, one relapsed. CONCLUSIONS: Our findings show that zinc supplementation can resolve permeability alterations in patients with Crohn's disease in remission. Improving intestinal barrier function may contribute to reduce the risk of relapse in Crohn's disease.

Adult↗

Bacterial translocation and its prevention in acute pancreatitis.

In recent years, bacterial translocation from the gut onto pancreatic necrosis has been proposed as the main cause of pancreatic infection and the consequent sepsis. Failure of the intestinal barrier, together with bacterial overgrowth due to motility changes and immunosuppression, constitute the pathways of the continuous pancreatic contamination from bacterial translocation in patients with severe acute pancreatitis. Selective decontamination, by using a combination of oral and intravenous antibiotics, has been reported to decrease the incidence of sepsis and the related mortality. Immunostimulation is another action to be taken to enhance the ability of the immune system to prevent bacterial translocation, by the entrapment and killing, by enterocytes, of the bacteria trying to translocate through the bowel wall. To keep the mucosal barrier function intact is one of the main issues in the prevention of bacterial translocation. This could be achieved by the adequate delivery of oxygen and nutrient supplementation. Enteral nutrition is a key factor, as it has been proven to maintain mucosal integrity, along with preventing deterioration of the immune function of the intestine.

Acute Disease↗

The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat.

Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased translocation of endotoxin to the liver, amd thus may potentiate the phenomenon of hepatocyte apoptosis. Exogenous administration of insulin-like growth factor-I (IGF-I) has been shown to enhance mucosal adaptation after small bowel resection in rats and also to accelerate repair of small intestinal mucosa after damage by the chemotherapy drug methotrexate. The aim of the current study was to determine the effect of exogenous IGF-I administration on hepatocyte apoptosis after bile duct ligation in rat. Male Sprague-Dawley rats weighing 250-300 g were randomized to three groups (n=6 in each group). Group 1 (control; C) underwent sham operation and was simultaneously treated with the same amount of normal saline. Group 2 (obstructive jaundice; OB) underwent common bile duct ligation without other manipulation. Group 3 (obstructive jaundice with IGF-I; OBIGF-I) underwent common bile duct ligation and simultaneous treatment with recombinant human IGF-I (a total dose of 1 mg in each rat, divided into six administrations; about 1 mg/kg/day). After 3 days, liver tissue was harvested and immediately snap-frozen in liquid nitrogen for histopathologic analysis and apoptosis measurements. Compared with the sham operation group (C), increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively). There was no significant difference in hepatocyte apoptosis (P=0.925) or ductular proliferation (P=0.385) between the sham control group (C) and the OBIGF-I group. Increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively).

Animals↗

Bowel wall thickening in infants with food allergy.

BACKGROUND: Food allergy may be partly due to impairment of the intestinal barrier and is frequently associated with atopic dermatitis (AD) in early life. OBJECTIVE: To determine whether bowel wall thickening, as demonstrated by US, is useful for the identification of food allergy. MATERIALS AND METHODS: We used US to study eight infants with food allergy and ten non-allergic controls to clarify whether specific intestinal findings in the jejunum, ileum and colon are present in infants with AD who have food allergy. RESULTS: Wall thickening was observed in all eight patients with food allergy, but only in the jejunum; it disappeared after elimination of suspected dietary allergens. Bowel wall thickening returned in the two allergic patients who received a food challenge test. CONCLUSIONS: Wall thickening of more than 2 mm on US in the jejunum in infants with AD may be a useful marker to evaluate the presence of food allergy and therapeutic effects.

Dermatitis, Atopic↗