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As the first line of defense against intestinal bacteria and toxins, intestinal epithelial cells are always exposed to bacteria or lipopolysaccharide (LPS), whereas pathogenic bacteria or LPS can cause intestinal epithelial cell damage. Previous studies have shown that konjac mannan oligosaccharides (KMOS) have a positive effect on maintaining intestinal integrity, and Bacillus subtilis (BS) can promote the barrier effect of the intestine. However, it is still unknown whether KMOS and BS have a synergistic protective effect on the intestines. In this study, we used the LPS-induced Caco-2 cell injury model and mouse intestinal injury model to study the synergistic effects of KMOS and BS. Compared with KMOS or BS alone, co-treatment with KMOS and BS significantly enhanced the activity and antioxidant capacity of Caco-2 cell, protected mouse liver and ileum from LPS-induced oxidative damage, and repaired tight junction and mucus barrier damage by up-regulating the expression of Claudin-1, ZO-1 and MUC-2. Our results demonstrate that the combination of KMOS and BS has a synergistic repair effect on inflammatory and oxidative damage of Caco-2 cells and aIIeviates LPS-induced acute intestinal injury in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Zhang, Wu, Ren, Liu and Wu.)

Background and Aims: Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes., Methods: The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn's disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry., Results: In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial-mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges., Conclusion: This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ulcerative colitis is an idiopathic inflammatory condition of the colon that may require surgical intervention including proctocolectomy and either ileal pouch-anal anastomosis or in the pediatric population, low ileorectal anastomosis (IRA). Often, subsequent physiologic alteration (or colonic metaplasia) occurs in the anastomosed small bowel that includes changes in mucin content, villous blunting, and increased expression of WNT5A, a marker of colonic crypt regeneration. We developed a rat low IRA model to assess and study the development of colonic metaplasia., Materials and Methods: We subjected male Sprague-Dawley rats (n = 17) to total colectomy and low IRA surgery and evaluated healing periodically by endoscopic evaluation. The ileum upstream of the anastomosis was assessed by hematoxylin and eosin staining, and the mucin content was measured by high iron diamine-Alcian blue staining. Wnt5a transcripts were quantified by reverse transcription and quantitative polymerase chain reaction at the 8-wk study end point., Results: Although no gross endoscopic evidence of inflammation was seen throughout the course of the study, colonic metaplasia in the small bowel was detected in 7 out of 10 (70%) rats at the study end point. In rats with colonic metaplasia, enhanced expression of Wnt5a was evident at the study end point compared to levels in the terminal ileum at the time of surgery., Conclusions: Within 4-8 wk, the majority of rats subjected to IRA developed colonic metaplasia defined by villous blunting, changes in mucin content, and increased expression of Wnt5a. This model provides a method to study small bowel colonic metaplasia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Eruptive collagenoma is a rare disease. All of the previously reported cases were located on the skin. Here we report such a case occurring in esophagus and intestine., Case Presentation: Our patient is a Chinese woman. Two years ago, hundreds of small nodules were identified in her esophagus and intestine. The lesions were characterized by thickened hyalinized collagen fibers and haphazard neoplastic stellate cells. The tumor cells showed generally positive for vimentin and negative for h-CALD, CD34, desmin, CD163, AE1/AE3, CK7 and CK20. The nodules were blue with Masson Trichrome stain. The clinicopathological, immunohistochemical and histochemical features of the tumor were consistent with eruptive collagenoma. The patient was not given specific treatment after diagnosis, and a routine examination indicated that there was no progress for 2 years., Conclusion: Hitherto, this is the first case of eruptive collagenoma to have been reported occurring in esophagus and intestine.

NSAIDuse is limited due to the drugs' toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced byNSAIDs is dependent on bile secretion and is reported to increase the growth of a number of bacterial species, including an enterococcal species,Enterococcus faecalis This study examined the relationships between indomethacin (INDO)-induced intestinal injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci, and the contribution of bile secretion to these pathological responses. Rats received either a sham operation (SO) or bile duct ligation (BDL) prior to administration of two daily subcutaneous doses of saline orINDO, and 24 h later, biopsies of ileum and liver were collected for plating on selective bacterial media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess intestinal bleeding. Of the four treatment groups, onlySO/INDOrats experienced a significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating thatBDLattenuatedINDO-induced intestinal injury/bleeding. Ileal enterococcal colony-forming units were significantly increased (500- to 1000-fold) inSO/INDOrats. Of all groups, only theSO/INDOrats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated thatINDO-induced intestinal injury andE. faecalisovergrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with theNSAID Bile secretion plays an important role inINDO-induced gut injury and appears to support enterococcal overgrowth of the intestine.NSAID-induced enterococcalSBOmay be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Objective: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue., Materials and Methods: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA., Results: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 μmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1β (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1β, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group., Conclusion: In this study, ileal damage caused by MTX was inhibited by RST., (© 2015 S. Karger AG, Basel.)

Background: Intestinal ischemia/reperfusion injury can be caused by surgical procedures and inflammatory bowel disease. It is normally associated with the increased production of free radicals and changes in the enteric nervous system., Aims: Given the antioxidant and neuroprotective properties of resveratrol, the present study assessed its influence on oxidative stress in the intestinal wall and the morphology of myenteric neurons in the ileum of rats subjected to ischemia/reperfusion., Methods: Resveratrol was orally administered daily at a dose of 10 mg/kg for 5 days. Changes in the ileum response to ischemia after 45 min were investigated followed by 3 h reperfusion. Lipoperoxide and carbonylated protein levels, and the activity of the antioxidant enzymes glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase were measured following ischemia/reperfusion injury., Results: The density and morphometry of the general neuronal population, nitrergic neurons and glial cells, and morphometry of VIP varicosities in the ileum were also studied. Lipoperoxide and carbonylated protein levels were 171 and 40% higher during the ischemia/reperfusion, respectively, compared to control cohorts, and resveratrol attenuated these values. The glutathione ratio was 64% lower during ischemia/reperfusion, compared to control cohorts. Resveratrol increased the reduced/oxidized glutathione ratio, attenuated the changes in the activity of the antioxidant enzymes and the detrimental morphologic changes caused by ischemia/reperfusion in the general neuronal population and nitrergic neurons., Conclusions: Oral treatment with resveratrol reduced the oxidative stress in the ileum and attenuated the morphologic changes that occurred in the myenteric plexus of the ileum in rats subjected to ischemia/reperfusion.

To evaluate the effects of exogenous ghrelin or obestatin on intestinal injury and accompanying pulmonary injury, intestinal ischemia-reperfusion (I/R) was induced in rats by obstructing the superior mesenteric artery for 60min, whereas laparotomy was performed in the sham group. At the beginning of the 90-min reperfusion period, the rats were injected with obestatin (100μg/kg), ghrelin (10ng/kg), or saline intravenously (iv). At the end of reperfusion, the blood, ileum, and lung samples were taken for the histological and biochemical assays. In the saline-treated I/R group, the increased serum interleukin (IL)-1β level, high damage scores, and elevated tissue malondialdehyde level and collagen content in both tissues were significantly reduced by obestatin or ghrelin. Increased ileal myeloperoxidase activity of the saline-treated I/R group was reduced by treatment with obestatin or ghrelin, whereas increased pulmonary myeloperoxidase activity was reduced with administration of obestatin. Increased DNA fragmentation in the ileum of the saline-treated I/R group was reduced by both peptides. Elevated luminol-lucigenin chemiluminescence levels and nuclear factor kappa B (NF-κB) messenger RNA (mRNA) expression in the ileum of the saline-treated-I/R group were significantly decreased by obestatin or ghrelin treatment. I/R-induced depletion of the antioxidant glutathione in both ileal and pulmonary tissues was prevented with either obestatin or ghrelin treatment. Administration of either obestatin or ghrelin exerts similar protective effects against I/R-induced ileal and pulmonary injury, thus warranting further investigation for their possible use against ischemic intestinal injury., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To investigate the protective effect of bifidobacterium in endotoxin-induced intestinal injury in preweaning rats., Methods: Preweaning rats were randomly divided into three groups (n = 40 for each): a control group (group C), a model group (group E) and a treatment group (group T). Both groups E and T were intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg (5 mg/L in normal saline), and group T was intragastrically administrated with bifidobacterium suspension (2.0 × 10(9) CFU/mL, 0.5 mL each time, twice a day, until the end of the experiment) 7 d before LPS administration. Group C was intraperitoneally injected with normal saline. After intraperitoneal injection and intragastric administration, the rats were placed back to the initial cage to receive breast feeding. The rats were killed at 2, 6, 12, 24 or 72 h, respectively, after endotoxin or physiological saline injection to collect serum and ileal tissue samples. Myeloperoxidase (MPO) contents in serum and ileum were detected at different times, and expression of ileal defensin-5 mRNA was evaluated by reverse transcription-polymerase chain reaction., Results: Serum and ileal MPO contents in group E were significantly higher than those in group C (serum contents: 107.50 ± 17.70 vs 157.14 ± 24.67, P < 0.05; ileal contents: 1.03 ± 0.21 vs 1.57 ± 0.33, P < 0.05), which peaked at 12 h and 6 h, respectively. MPO contents in group T were significantly lower than those in group E (serum contents: 114.38 ± 24.56 vs 145.25 ± 23.62, P < 0.05; ileal contents: 1.25 ± 0.24 vs 1.57 ± 0.33, P < 0.05). The expression of defensin-5 mRNA in group E was significantly higher than that in group C (0.953 ± 0.238 vs 0.631 ± 0.146, P < 0.05), which peaked at 2 h, and then decreased gradually. The expression of defensin-5 mRNA in group T was significantly lower than that in group E (0.487 ± 0.149 vs 0.758 ± 0.160, P < 0.05) apparently in 24 h. The expression of defensin-5 mRNA at 2 h in group T was significantly higher than that in group C (0.824 ± 0.158 vs 0.631 ± 0.146, P < 0.05)., Conclusion: MPO and defensin-5 mRNA increase in preweaning rats with LPS-induced intestinal injury. Bifidobacterium protects the gut by inhibiting MPO activity, not by increasing defensin-5 secretion.

Aim: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction., Methods: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3(+), CD4(+) and CD8(+) T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay., Results: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer's patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8(+) T cells, driven by an increase in CD3(+) and CD8(+) T cells and a decrease in CD4(+) T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction., Conclusion: Intestinal obstruction can induce disruption of intestinal homeostasis.

Recent developments in the field of diabetes and obesity management have established the central role of the gut in glucose homeostasis; not only is the gut the primary absorptive site, but it also triggers neurohumoral feedback responses that regulate the pre- and post-absorptive phases of glucose metabolism. Structural and/or functional disorders of the intestine have the capacity to enhance (e.g.: diabetes) or inhibit (e.g.: short-gut syndrome, critical illness) glucose absorption, with potentially detrimental outcomes. In this review, we first describe the normal physiology of glucose absorption and outline the methods by which it can be quantified. Then we focus on the structural and functional changes in the small intestine associated with obesity, critical illness, short gut syndrome and other malabsorptive states, and particularly Type 2 diabetes, which can impact upon carbohydrate absorption and overall glucose homeostasis.

Colonoscopic evaluation of mucosal tissues after allogeneic hematopoietic stem cell transplantation (HSCT) is very useful in evaluating pathogenesis and diagnosis of intestinal graft-versus-host disease (GVHD). However, information on the timing and sites of biopsies and the immunohistological evaluation of mucosal tissues for diagnosing intestinal GVHD, especially following reduced-intensity (RIC) regimens, remains very limited. A total of 33 patients with histologically proven GVHD after allogeneic HSCT with RIC (n = 23) and myeloablative conditioning (MAC, n = 10) regimens were enrolled in the present study. Colonoscopy was performed due to gastrointestinal symptoms, especially diarrhea and anorexia. Sites of biopsies with the worst histopathological grading were the terminal ileum in 67 % of patients. In the RIC group, the onset of diarrhea prior to colonoscopy examination was later (median: RIC, 57 vs. MAC, 27 days) and the number of patients who developed abdominal pain tended to be higher (RIC, 70 % vs. MAC, 30 %). A lower number of CD4+ cells and a higher ratio of Foxp3+ cells to CD4+ cells were detected in the involved lesions of intestinal GVHD following RIC. These differences in the RIC and MAC groups suggest that regimen-specific therapeutic strategies are required for diagnosing intestinal GVHD.

Aim: To investigate different methods of creating incomplete intestinal obstruction in a rat model and to compare their electrophysiologic, morphologic and histologic characteristics., Methods: Rat ileum was partially obstructed by the respective application of: braided silk (penetrated the mesentery and surrounded intestine); half ligation (penetrated directly and ligated 1/2 cross-section of the intestine); wide pipe (6 mm in width, surrounded the intestine); narrow pipe (2 mm in width, surrounded the intestine). A control was also included (no obstruction). Various behavioral and electrophysiologic variables, as well as morphologic and immunohistochemical observations were recorded by blinded investigators at different time points (12, 24, 48, 72 h), including daily general condition, ileal wet weight and circumference, macromorphous and micromorphous intestine, bowel movement capability in vivo and in vitro, slow wave and neural electrical activity, and the number of c-Kit positive interstitial cells of Cajal (ICC)., Results: Despite being of a similar general condition, these methods resulted in different levels of obstruction in each group compared with the control at different time points (12, 24, 48, 72 h). However, these fields of the wide pipe rat showed significantly differences when compared with the other three obstructed groups at 12 to 72 h, including macroscopic and histological presentation, intestinal transit ratio and contractility, circumference and wet weight, amplitude and frequency of nerve electrical discharge and slow wave, and ICC numbers (all P < 0.01)., Conclusion: The wide pipe rat method is significantly more reliable and stable than the other methods of obstruction, demonstrating that use of the wide pipe method can be a useful model of incomplete intestinal obstruction.

Unlabelled: Cecal endometriosis and ileocolic intussusception due to a cecal endometriosis is extremely rare. We report a case of a woman who presented an ileocecal intussusception due to a cecal endometriosis. The patient gave two months history of chronic periombilical pain requiring regular hospital admission and analgesia. The symptoms were not related to menses. A laparotomy was performed and revealed an ileocolic intussusception. The abdominal exploration did not find any endometriosis lesion. Ileocaecal resection was performed. Microscopic examination showed a cystic component, lined by a regular cylindric epithelium. Foci of endometrial tissue were observed in the cecal subserosa and muscularis mucosal, with irregular endometrial glands lined by cylindric epithelium without atypia immunostained with CK7, and characteristic endometrial stroma immunostained with CD10. Cecal endometriosis and ileocolic intussusception due to a cecal endometriosis is extremely rare. Diagnose of etiology remains challenging due to the absence of clinical and radiological specific characteristics., Virtual Slide: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2975867306869166.

Low-grade endometrial stromal sarcoma (LESS) is an uncommon uterine malignancy. Occasionally, it may develop in extrauterine endometriotic lesions and present morphological characteristics mimicking various neoplasms, making its diagnosis very challenging. We report a rare case of a 56-year-old woman presenting with a pelvic mass, initially presumed to be of ovarian origin. After surgical excision the diagnosis of a LESS arising from foci of endometriosis of the terminal ileum was established. Pelvic lymph nodes and omentum were also infiltrated. The patient received adjuvant chemotherapy and medroxyprogesterone; she is alive with no evidence of disease after a follow-up of 38 months. Immunohistochemical characteristics of the tumor are very important for the differential diagnosis of this rare neoplasm and include diffuse strong positivity for CD 10, estrogen receptor expression and CD 34 negativity., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Objectives: Previous studies have suggested that gastrointestinal integrity is compromised after cardiopulmonary bypass (CPB). We compared the effects of prolonged minimized (MCPB) and conventional CPB (CCPB) on intestinal mucosal integrity by determining mucosal damage, epithelial cell proliferation rate and distribution of tight junction proteins in a porcine model., Design: Fourteen animals were randomly assigned to undergo 240 minutes of mild hypothermic MCPB or CCPB. Ileal and colonic biopsies were obtained prior and at the end of CPB. Mucosal damage was determined under light microscopic evaluation. Immunohistochemistry was used to investigate epithelial expression of Ki-67 as a measure of cell proliferation rate and claudin-1, 2, 3, 4, 5, and 7 as elements of tight junctions., Results: In colonic biopsies, independent of the circuit type used, moderate mucosal damage was observed as indicated by focal epithelial damage, increased epithelial cell proliferation and decreased expression of tight junction protein claudin-4., Conclusions: Colonic mucosal damage was observed similarly in MCPB and CCPB. Based on these results, the effects of MCPB on intestinal mucosal stability are similar to those of CCPB.

Background: Intussusception in an adult must make us suspect the presence of a tumor (benign or potentially dangerous) as the most frequent cause. Accurate diagnosis is of great importance in order to provide appropriate treatment and improve patient prognosis., Clinical Case: We report the case of a 42-year-old male with abdominal pain. We performed a CT and found a small bowel intussusception. Definitive diagnosis according to the surgical specimen was inflammatory fibroid polyp (Vanek's polyp)., Conclusions: Vanek's polyp is a benign lesion that occurs most frequently in the stomach and secondarily in the small bowel. Generally, it is uncommon, and its etiology is not completely known. Accurate diagnosis is done with immunohistochemistry. Because of the consequences that depend on the size and location of the lesion, it may be considered a malignant lesion. Treatment is resection.

Background: The purpose of this study is to investigate the protective effects of Ginkgo biloba extract (EGb 761) in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury., Methods: One-day-old Wistar albino rat pups (n = 21) were randomly divided into 3 groups: group 1 (control, untreated and not exposed to H/R, n = 7), group 2 (untreated but exposed to H/R, n = 7), and group 3 (EGb 761 + H/R, n = 7). Ginkgo biloba extract was administered (100 mg/kg per day, subcutaneously) to group 3 for 3 days. On the fourth day, all animals except controls were exposed to H/R and were killed 6 hours after H/R. Histopathologic injury scores (HIS), malondialdehyde, glutathione (GSH), GSH-peroxidase (Px) activities, and nitric oxide (NO) levels were measured on intestinal samples., Results: Although the control group had normal HIS, group 2 had grade 3 HIS. In contrast, group 3 had minimal HIS, and these results were significantly better than those of group 2 (P < .001). Malondialdehyde and NO levels of group 3 were significantly lower than those of group 2 (P < .01). Glutathione and GSH-Px activities of group 1 were higher than those of groups 2 and 3 (P < .05). However, there were no significant differences for GSH and GSH-Px activities between groups 2 and 3., Conclusions: This study showed that hypoxia and NO contributed to the pathogenesis of H/R-induced intestinal injury and that prophylactically administered EGb 761 had a protective effect on bowel injury., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Intestinal ischemia/reperfusion causes tissue hypoxia and damage, leading to the pathophysiology of inflammation. The aim of this study was to investigate the effects of glutamine on the tissue injury caused by ischemia/reperfusion of the gut. Ischemia/reperfusion injury of the intestine was caused by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by the release of the clamp allowing reperfusion for 1h. This procedure results in splanchnic artery occlusion-injury. Based on our findings we propose that the amino acid glutamine, administered 15 min before reperfusion at the dose of 1.5mg/kg, i.v. may be useful in the treatment of various ischemia and reperfusion diseases. The present study was performed in order to determine the pharmacological effects of glutamine ischemia/reperfusion-induced intestinal injury in rats. In particular, to gain a better insight into the mechanism(s) of action of glutamine, we evaluated the following endpoints of the inflammatory response: (1) histological damage; (2) neutrophil infiltration of the reperfused intestine (MPO activity); (3) NF-kappaB activation and cytokines production; (4) expression of ICAM-1 and P-selectin during reperfusion; (5) nitrotyrosine and poly-ADP-ribose formation; (6) pro-inflammatory cytokine production; (7) inducible nitric oxide synthase expression; (8) apoptosis as shown by TUNEL staining and (9) Bax/Bcl-2 expression., (2010 Elsevier B.V. All rights reserved.)

The present study was undertaken to determine whether resveratrol (RVT) could ameliorate ionizing radiation-induced oxidative injury. After a 10-days pre-treatment with RVT (10 mg/kg/day p.o.), rats were exposed to whole-body IR (800 cGy) and the RVT treatment was continued for 10 more days after the irradiation. Irradiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the liver and ileum tissues. Similarly, plasma lactate dehydrogenase and pro-inflammatory cytokine levels, 8-hydroxy-2'-deoxyguanosine and leukocyte apoptosis were elevated, while antioxidant-capacity was reduced in the irradiated rats as compared with the control group. Furthermore, Na(+), K(+)-ATPase activity was inhibited and DNA fragmentation was increased in the ileal tissues. Resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. In conclusion, supplementing cancer patients with adjuvant therapy of resveratrol may have some benefit for a more successful radiotherapy.

Absence of enteric neurons is associated with thickening of the intestinal muscularis externa in Chagas' disease. The thickening is due to hyperplasia and hypertrophy of the smooth muscle cells and increased extracellular matrix components. The influence of the nervous system on the structure of the smooth muscle cells and its associated matrix has been poorly investigated. An experimental model of denervation of the ileum in rats was performed by application of the surfactant agent benzalkonium chloride that selectively destroys the myenteric plexus. Three months later, ileal tissue samples were obtained and studied by histochemistry and transmission electron microsocopy. Sham operated rats were used as controls. The diameter of collagen fibrils was evaluated in electron micrographs. The histopathological analysis showed thickening of the muscular layer. The thin and weakly arranged collagen and reticulin fibers surrounding the smooth muscle cells, observed in control cases by Picrosirius polarization (PSP) stain method, corresponded to a population of loosely packed thin collagen fibrils of uniform diameters (mean=29.16 nm) at the ultrastructural level. In contrast, the thick and strongly birefringent fibers around the muscle cells, observed in the treated group, stained by PSP, corresponded to densely packed thicker fibrils with large variation in diameter (mean=39.41 nm). Comparison of the data demonstrated statistically significant difference between the groups suggesting that the replacement of loosely arranged reticulin fibers by fibrous tissue (with typical collagen fiber), may alter the biomechanical function resulting in impairment of muscular contraction.

We evaluated the effects of N-hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M(2) and M(3) receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M(1) selective), methoctramine (M(2) selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M(1)/M(3) selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA(2) values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M(3) receptor subtype in all groups. Furthermore, N-hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M(2) and M(3) receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.

A 38-year-old woman with history of prior adrenalectomy for Cushing's syndrome presented with intermittent right lower quadrant (RLQ) abdominal pain, nausea, bloating, and non-bloody diarrhea for 2 months. Symptoms were not related to her menstrual periods. Examination revealed only an ill-defined mass in the RLQ. Investigations for infectious causes, inflammatory bowel disease, and carcinoid tumor were negative. Computed tomography (CT) demonstrated a terminal ileal mass with mesenteric stranding and dilatation of the proximal bowel. At laparotomy, a fibrotic, terminal ileal mass with matted adhesions involving the mesentery and retroperitoneum was resected. Histopathological examination identified multiple foci of endometriosis extending from the serosal surface into the mucosa of the terminal ileum. Immunostaining revealed E- and P-cadherin, but not N-cadherin immuno-positivity. Mucosal involvement without cyclical menstrual symptoms and intestinal obstruction is an unusual presentation of intestinal endometriosis. Although the mechanism of endometriosis is not clear, the role of cell adhesion molecules such as cadherins has received attention. Increased expression of E- and P-cadherin and decreased N-cadherin expression in our patient demonstrates differential expression of these cadherins in endometriotic tissue. Future studies may investigate patterns of differential expression of these cadherins in a series of cases to elucidate the mechanisms of migration of endometriotic tissue.

Backgrounds/aims: Gastrointestinal decompression by nasogastric or intestinal tubes developed in 1930s has been the only treatment modality for inoperable intestinal obstruction. We hypothesized that the octreotide, a potent inhibitor of intestinal secretion, has a therapeutic potential in intestinal obstruction., Methods: Forty Sprague-Dawley rats were randomly assigned to four groups. The rats were subjected to complete or partial ileal obstruction. The treated rats received octreotide (100 microgram/kg) while the controls received the same quantity of saline every 12 hours for 24 or 48 hours. After 24 or 48 hours, the volumes of the small bowel contents were measured. The volumes of supernatant and the concentrations of electrolytes in the small bowel contents after centrifugation were also analyzed. The ileal segments proximal to obstruction were harvested, fixed, and stained, and the pathological changes were evaluated with mucosal damage scores., Results: There were no statistical differences in the volume and the electrolyte composition of intestinal fluid among the 4 groups. In the 48 hour complete obstruction group, the octreotide-treated rats showed statistically lower mucosal damage scores than the control rats (p<0.05)., Conclusions: Octreotide exerts mucosal protecting effect on the complete intestinal obstruction rat model.

Purpose: The aim of this study is to analyze the relationship between the changes in blood and peritoneal fluid and the duration of mechanical intestinal obstruction., Methods: A mechanical intestinal obstruction was surgically carried out in 52 Wistar albino rats. The blood and peritoneal fluid were sampled immediately (Group 1, n=13), and at 6 hours (Group 2, n=13), at 24 hours (Group 3, n=13), and at 48 hours (Group 4, n=13) following the procedure., Results: Blood and peritoneal fluid ammonia concentrations, as well as blood aldolase activity have risen progressively over time (p<0.05), although not all pair-wise comparisons were statistically significant (P>0.05)., Conclusions: Our data suggest that peritoneal fluid and blood ammonia levels and blood aldolase levels rise according to duration of the intestinal obstruction. Since the results were not available to determine cut-off levels, future research is required to confirm these results and determine whether ammonia or aldolase can be used in clinical practice to predict the presence and duration of a mechanical intestinal obstruction.

Neuronal nicotinic acetylcholine receptors (nAChR) are composed of 12 subunits (alpha 2-alpha 10 and beta 2-beta 4), which play the central role in autonomic transmission. beta 4 subunits are abundantly expressed in autonomic ganglia, forming acetylcholine binding sites and ion channels with alpha 3 or alpha 3 and alpha 5 subunits as pentameric receptors. To investigate the physiological and pharmacological properties of beta 4 subunits in autonomic ganglia, we measured autonomic functions in knockout mice lacking nAChR subunit beta 4 (beta 4(-/-)) and wild-type mice. beta 4(-/-) mice had an attenuated bradycardiac response to high frequency (60 pulse/s) vagal stimulation, as well as an increased sensitivity to hexamethonium blockade at low dose (3 mg/kg) and a reduced ileal contractile response to the nicotinic agonists cytisine, dimethylphenylpiperazinium iodide, nicotine (10 mg/kg each), and epibatidine (0.1 mg/kg). The results suggest that beta 4 subunits are important components of nAChRs in autonomic ganglia. Deficiency of beta 4 subunits altered ion channel properties, conductance, and sensitivity and affinity of receptors to agonists and antagonists, affecting ganglionic transmission.

Objective: To study the influence of apoptosis of intestinal epithelial cells occurring as a result of reperfusion after burn shock on the intestinal barrier., Methods: Fifty Wistar rats were subjected to a 30% TBSA full thickness burn, and normal saline (40 ml/kg) was given intraperitoneally immediately after the injury (group A). Ten rats served as a sham control group. The experimental group B consisted of 50 rats with identical injuries, but the normal saline was not given until 6h after the injury. Apoptosis of intestinal epithelial cells was verified by DNA fragmentation, DNA agarose gel electrophoresis, TUNEL and electron microscope (EM), and DNA fragmentation rate was expressed as ap%. The D-lactic acid in portal vein blood and intestinal diamine oxidase (DAO) were determined to evaluate the permeability and integrity of intestinal mucosal epithelium., Results: The ap% of intestinal epithelium group B was higher than in that of group A (P<0.05 or 0.01), and its amplitude peaked at 12h for both groups. Typical DNA ladder pattern was seen in electrophoresis in both groups. Apoptotic cells were discerned on the tips of the ileal villi at 3h postscald by TUNEL and EM in the group B, and they appeared earlier than in the group A. There was a significant positive correlation between the ap% and the level of D-lactic acid (group A: r=0.817, P<0.05; group B: r=0.727, P<0.05). On the other hand, a significant negative correlation was found between the ap% and the DAO values (group A: r=-0.937, P<0.01; group B: r=-0.836, P<0.05)., Conclusion: Apoptosis occurred in enterocytes after scald injury this pathological change might contribute to a breach of integrity of intestinal epithelium, leading to a compromise in its barrier function. Delayed fluid resuscitation might lead to an earlier and higher degree of apoptosis of the intestinal epithelial cells.

The aim of the present study was to determine whether the ET(A) receptor antagonist LU135252 can protect the mesenterium against ischaemia/reperfusion (I/R) damage. Direct occlusion of the superior mesenteric artery was performed for 30 min in two groups of dogs. Declamping was followed by 90 min of reperfusion. Mesenteric release of ET-1 was studied in series 1 (n=6). In series 2, 5 min before cross-clamping, the treated group (n=7) received an intravenous bolus of LU135252 (5 mg/kg), whereas the control group (n=6) was given vehicle. Mean arterial blood pressure and mesenteric blood flow were recorded. Mesenteric venous and systemic arterial serum lactate and glucose, plasma creatine kinase and free radical concentrations were determined at 15 min intervals. Ischaemia for 30 min induced a significant increase (P<0.05) in mesenteric ET-1 release (1594+/-526 pg/min, compared with 343+/-258 pg/min at baseline), which had returned to baseline after 20 min of reperfusion. LU135252 administration significantly decreased mesenteric blood flow during ischaemia (204+/-23%) compared with controls (320+/-34%, P<0.05). In contrast, mesenteric blood flow was higher in the treated group (120+/-19% compared with 82+/-7%; P<0.05) after 90 min of reperfusion. Mesenteric lactate production was reduced by ET(A) antagonist administration under ischaemia (0.77+/-0.02 mmol/l) compared with controls (1.36+/-0.04 mmol/l; P<0.01). Lower levels of venous creatine kinase were present in the treated group during ischaemia as well as after reperfusion (120+/-7% compared with 150+/-16%; P<0.01). Administration of LU135252 also improved the total scavenger capacity of the mesenteric bed during ischaemia [(15.9+/-3.9)x10(6) compared with (6.4+/-3.6)x10(6) relative light units; P<0.05] and early reperfusion [(8.7+/-3.1)x10(6) compared with (1.1+/-2.9)x10(6) relative light units]. Thus ET-1 is involved in I/R-induced disturbances in the intestine. LU135252 seems to counteract these changes, in part by increasing the antioxidant capacity of the mesenterium.

Inflammatory pseudotumours are the morphological expression of diverse processes such as reactive/reparative, infective, and neoplastic. This paper reports an example of intestinal inflammatory pseudotumour, with identification of a newly characterized bacterium in the lesion. The patient presented with intestinal obstruction. Laparotomy revealed a tumour in the terminal ileum causing stricture, and multiple enlarged regional lymph nodes. Histologically, the tumour and lymph nodes were composed of plump spindle cells disposed in a vague storiform pattern, and associated with lymphocytes and plasma cells. Immunohistochemical studies showed that most of the spindle cells were histiocytes (CD68 positive), prompting a search for a bacterial aetiology, akin to mycobacterial spindle cell pseudotumour. All histochemical stains for micro-organisms were unrewarding. Ultrastructural studies, however, revealed abundant bacteria within the spindle histiocytes. Polymerase chain reaction, using conserved oligonucleotide primers complementary to the 16S rRNA genes of eubacteria, was employed to amplify 16S rRNA gene fragments directly from the involved lymph node tissue. Phylogenetic analysis of the amplified DNA sequences revealed an organism with 99% sequence conformity to Pseudomonas veronii, a bacterium which has hitherto not been implicated in human infection. The importance of searching for an infective agent in inflammatory pseudotumour in the appropriate setting is re-emphasized., (Copyright 2000 John Wiley & Sons, Ltd.)

Background & Aims: We explored the role of biliary phosphatidylcholine (PC) in protection of the intestinal mucosa against bile salt (BS)-induced intestinal injury and how this property may be blocked by indomethacin (Indo), a nonsteroidal anti-inflammatory drug (NSAID) that is secreted into the bile., Methods: We performed in vivo studies in which bile was collected over a 2-hour period after rats were intragastrically administered Indo (25 mg/kg) or an equivalent volume of saline (controls). The bile samples (some of which were supplemented with PC) were then instilled into a loop of distal ileum of anesthetized rats. After a 30-minute exposure period, we measured the hemoglobin concentration of the ileal loop fluid, as an index of bleeding, and mucosal contact angles, as an index of surface hydrophobicity. A similar in vivo experiment was performed in which model bile containing 5 mmol/L each of the BS, sodium deoxycholate, PC, or Indo, alone and in combination, was instilled into ileal loops. In our in vitro test system, human erythrocytes were exposed to the above biliary constituents, and hemolysis was measured spectrophotometrically., Results: Bile from Indo-pretreated rats decreased the surface hydrophobicity and induced bleeding of ileal loops in comparison with control bile, and both NSAID-induced changes were reversed if PC was added to the bile. Similarly, synthetic BS caused gastrointestinal bleeding, decreased ileal contact angles, and induced erythrocyte hemolysis, all of which were reversed by addition of equimolar PC. This protective role of PC in both the in vivo and in vitro systems was partially blocked by Indo, although the NSAID had no effect on these properties on its own., Conclusions: These findings support the hypothesis that PC protects the intestinal mucosa against injurious actions of BS, possibly by forming less toxic mixed micelles. Indo and perhaps other NSAIDs that enter the bile may damage the mucosa, not by a direct action, but by competing for the available protective PC molecules.

The aim of the present study was to investigate the protective effect of the pineal secretary product melatonin in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were sacrificed for tissue histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAO-shocked rats developed a significant increase of tissue myeloperoxidase and malondialdehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 hr after reperfusion). Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localized in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. Melatonin (applied at 3 mg/kg, 5 min prior to reperfusion, followed by an infusion of 3 mg/kg per hr), significantly reduced ischemia reperfusion injury in the bowel as evaluated by histological examination. This prevented the infiltration of neutrophils into the reperfused intestine, is evidenced by reduced myeloperoxidase activity and reduced lipid peroxidation. This was evaluated by malondialdehyde activity which reduced the production of peroxynitrite during reperfusion, markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats and improved their survival. Taken together, our results clearly demonstrate that melatonin treatment exerts a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury.

We investigated the pathogenic role of nitric oxide (NO) in indomethacin-induced intestinal ulceration in rats. Nonfasting animals responded to a single administration of indomethacin (10 mg/kg, s.c.), resulting in multiple hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The damage was first observed 6 hr after indomethacin, the severity increasing progressively with time up to 24 hr later, accompanied with the gene expression of inducible NO synthase (iNOS) and the increase of nitrite and nitrate (NOx) contents in the mucosa. The ocurrence of damage was significantly prevented when iNOS induction was inhibited by dexamethasone given either once 0.5 hr before or twice 0.5 hr before and 6 hr after indomethacin. Likewise, aminoguanidine (a relatively selective iNOS inhibitor) reduced the severity of damage, irrespective whether given twice or as a single injection 6 hr after indomethacin. By contrast, the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) exhibited a biphasic effect, depending on the time of administration; the pre-administration worsened the damage, while the later administration reduced the severity of these lesions, yet both responses occureed in a L-arginine-sensitive manner. Pre-administration of L-NAME, but not aminoguanidine, significantly decreased NOx production in the intestinal mucosa of normal rats, while the increase of NOx production following indomethacin was significantly suppressed by the later administration of aminoguanidine as well as L-NAME. These results suggest that NO exerts a dual action in the pathogenesis of indomethacin-induced intestinal ulceration; NO generated by cNOS is protective against indomethacin, by maintaining the integrity of intestinal mucosa, while NO derived by iNOS plays a key pathogenic role in the ulcerogenic process.

Background & Aims: Patients with ileal disease, bypass, or resection are at increased risk for developing gallstones. In ileectomized rats, bilirubin secretion rates into bile are elevated, most likely caused by increased colonic bile salt levels, which solubilize unconjugated bilirubin, prevent calcium complexing, and promote its absorption and enterohepatic cycling. The hypothesis that ileal disease or resection engenders the same pathophysiology in humans was tested., Methods: Sterile gallbladder bile samples were obtained intraoperatively from 29 patients with Crohn's disease and 19 patients with ulcerative colitis. Bilirubin, total calcium, biliary lipids, beta-glucuronidase activities, and cholesterol saturation indices in bile were measured, and markers of hemolysis and ineffective erythropoiesis in blood were assessed., Results: Bilirubin conjugates, unconjugated bilirubin, and total calcium levels were increased 3-10-fold in bile of patients with ileal disease and/or resection compared with patients with Crohn's colitis or ulcerative colitis. Biliary bilirubin concentrations correlated positively with the anatomic length and duration of ileal disease. Endogenous biliary beta-glucuronidase activities were comparable in all groups, and both the hemogram and serum vitamin B12 levels were normal., Conclusions: This study establishes that increased bilirubin levels in bile of patients with Crohn's disease are caused by lack of functional ileum, supporting the hypothesis that enterohepatic cycling of bilirubin occurs.

Chronic diarrhea caused by bile acid malabsorption (BAM) is usually divided into three groups. Type 1 is associated with ileal disease or ileal resection; type 2 is idiopathic, and type 3 is BAM associated with certain predisposing conditions. We evaluated the applicability of the SeHCAT test as a routine investigation of different types of suspected BAM. Detailed information about 298 patients were obtained from retrospective review of patient records. All 68 patients with ileal resections had abnormal SeHCAT retention (median 0.6%; range 0-13%). Of 42 patients with non-resected Crohn's disease or radiation injury, BAM was found in 28 cases. A diagnosis of BAM type 2 was established in 33 of 150 patients with unexplained chronic diarrhoea. For patients tested for possible BAM type 3, the SeHCAT values were significantly lower compared to type 2 patients. For BAM type 1, the SeHCAT test is only recommended in non-resected patients. Idiopathic BAM seems to be more common than recognized. The presence of certain predisposing conditions might strengthen the indication for SeHCAT testing.

In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammatory mediator pathways. We previously demonstrated that Na+-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na+-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na+-K+-ATPase was reduced 50% and Na+-alanine cotransport was also reduced (5.8 +/- 1.2 in normal and 1.4 +/- 0.5 nmol/mg protein in inflamed; n = 6, P < 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 +/- 1.2 in normal and 21.5 +/- 3.2 pmol/mg protein in inflamed; n = 3, P < 0.05), suggesting a direct effect on the cotransporter itself. Na+-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cotransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.

Background: Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine., Aims: To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum., Methods: Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18-24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC., Results: In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum., Conclusion: Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.

Design and Methods: In order to evaluate its possible role in the pathogenesis of pouchitis we measured the release, into the incubation medium of leukotriene B4 from mucosal samples from patients with ileal pouch-anal anastomosis and correlated release with clinical, endoscopic and histological features., Results: Leukotriene B4 release was significantly elevated in patients with active pouchitis in comparison to those with a normal pouch mucosa (P < 0.007). No overlap was observed between leukotriene B4 levels from patients with active pouchitis samples and those obtained from individuals without pouchitis. Effective treatment of pouchitis was associated with a significant reduction in leukotriene B4 mucosal release to the incubation medium (P < 0.03). However, even in remission, levels of leukotriene B4 release remained significantly increased in these patients in comparison to people who never experienced pouchitis (P < 0.003). A modest correlation was observed between pouchitis disease activity index and leukotriene B4 release (r = 0.596; P < 0.01)., Conclusion: These results suggest that the increased production of leukotriene B4 may be implicated in the pathogenesis of pouchitis. The persistence of an increased mucosal release of leukotriene B4 in pouchitis patients during clinical remission suggests the presence of a chronic, ongoing, underlying inflammatory process.

Objective: To evaluate the hypothesis that splanchnic ischemia and mucosal hypoxia are responsible for lipopolysaccharide-induced intramucosal acidosis in pigs., Design: Prospective, randomized, unblinded study., Setting: Surgical research laboratory at a large, university-affiliated medical center., Subjects: Anesthetized, mechanically ventilated swine., Interventions: Pigs were infused with lactated Ringer's solution (12 mL/kg/hr) and, starting at 30 mins, 25-mL boluses of dextran-70 (maximum 15 mL/kg/hr) to maintain cardiac output at 90% to 110% of the baseline value for each pig. Ileal mucosal hydrogen ion concentration was measured tonometrically. A segment of distal ileum was exteriorized, opened, and placed on a platform to permit measurement of mucosal PO2, using an array of Clark-type microelectrodes and a computerized data acquisition and analysis system. Mucosal perfusion was measured using laser-Doppler flowmetry. The control group (n = 4) received no further interventions. Pigs in the lipopolysaccharide group (n = 6) were infused with 150 micrograms/kg of Escherichia coli lipopolysaccharide over 60 mins. To assess the effect of mucosal acidosis on mucosal PO2 in nonendotoxemic animals, intramucosal hydrogen ion concentration, mucosal PO2, and mucosal perfusion were measured in pigs rendered hypercarbic through deliberate hypoventilation (hypercarbia group; n = 4)., Measurements and Main Results: Infusion of lipopolysaccharide resulted in a significant increase in intramucosal hydrogen ion concentration. However, in the lipopolysaccharide group, mucosal perfusion did not change significantly and mucosal PO2 increased significantly. In the hypercarbia group, hypercarbia was associated with significant increases in both intramucosal hydrogen ion concentration and mucosal PO2., Conclusions: Mucosal hypoxia is not responsible for lipopolysaccharide-induced mucosal acidosis in this normodynamic pig model of septic shock. A rightward shift of the oxyhemoglobin dissociation curve (the Bohr effect) can explain the increase in mucosal oxygenation observed in endotoxemic pigs.

The ulceration-associated cell lineage (UACL) develops in the human gastrointestinal mucosa after ulceration; it grows out from the bases of adjacent crypts and ramifies in the lamina propria to form a new gland, finally giving rise to a duct by which the glandular secretion and indeed cells are carried to the surface. Using immunocytochemistry and in situ hybridization with 35S-labelled riboprobes, we have defined the pattern of trefoil peptide gene expression (pS2; human spasmolytic polypeptide, hSP), epidermal growth factor/urogastrone (EGF/URO), and the distribution of cell proliferation during the development of the UACL, as indicated by immunostaining for proliferating cell nuclear antigen (PCNA). Our studies reveal that the morphogenesis of the UACL shows a marked morphological resemblance to developing Brunner's glands; the pattern of trefoil peptide gene expression during UACL development is also very similar. However, trefoil peptide gene expression in the mature UACL complex is unique amongst gastrointestinal cells. The mature UACL shows a distinctive proliferative organization: while the early buds and glands are non-proliferative, apparently being fed by cells from the parent crypts, a definitive proliferative zone develops within the duct. This, of course, corresponds to the location of the gastric gland proliferative zone. We propose that while the UACL shows novel features, it shares its differentiation programme with Brunner's glands, but its pattern of cell renewal eventually is that of the gastric gland.

Objectives and Methods: The performances and the clinical significance of a simplified version of the 75SeHCAT test which measures ileal absorption of bile salts were assessed in 23 healthy subjects and 106 patients. Corporeal retention of the marker was measured using an uncollimated gamma-camera., Results: In healthy subjects, the 75SeHCAT retention was lower in the group of 9 with an osmotic diarrhoea induced by a PEG solution than in the group of 14 tested in normal conditions (22 +/- 4% vs 44 +/- 4%; P < 0.01). The reproducibility of the measure was good (r = 0.93; P < 0.001). The sensibility and specificity of the test for the diagnosis of ileal involvement were 79% and 90% respectively. Bile acid malabsorption was evidenced in 38% of patients with functional diarrhoea (59% and 28% in patients with and without previous cholecystectomy respectively; P < 0.02). In patients with fonctional diarrhoea, a correlation was evidenced between the orofaecal transit time and the 75SeHCAT retention (r = 0.66; P < 0.001) and cholestyramine improved diarrhoea in 8 out of 11 patients with 75SeHCAT malabsorption and in 2 out of 5 patients with normal test. These results show that the 75SeHCAT test is accurate and that bile acid malabsorption, frequently evidenced in functional diarrhoea, is correlated with an acceleration of intestinal transit.

Hypoxanthine has been shown to be a sensitive and more specific measure of hypoxia than lactate in several body fluids other than peritoneal fluid. An experimental study was conducted to determine the value of peritoneal fluid hypoxanthine besides lactic acid levels in detecting vascular compromise of the intestine. Thirty male guinea pigs were divided in 3 groups each containing 10 animals. Groups comprised of sham operation control, simple intestinal obstruction and intestinal obstruction with vascular compromise. Lactic acid and hypoxanthine levels were determined in peritoneal lavage effluents. Peritoneal fluid lactic acid levels increased after 4 hours of intestinal obstruction with vascular compromise (p < 0.01) but not in simple intestinal obstruction and sham operation control groups. No detectable amount of hypoxanthine could be found in any of the fluid samples. It is concluded that unlike in other body fluids hypoxanthine is not present in peritoneal fluid and does not become evident after vascular compromise of the intestine.

We report a 60-year-old man with intermittent diarrhea for 15 years which was worsened by cholecystectomy. The results of routine laboratory tests, x-ray studies of the gut, and endoscopy were normal. Fecal fat excretion was normal, but total bile acid excretion was increased in the alkaline feces. The retention of 75SeHCAT was low. Jejunal mucosal biopsy showed normal mucosa. Ileal biopsy was performed at ileoscopy some 10 to 15 cm proximal to the ileocecal valve. Scanning-electron and light microscopy showed a transitional zone between villous atrophy in the distal and normal mucosa in the proximal part of the biopsy specimen. The response of diarrhea to cholestyramine treatment was unequivocal, suggesting bile acid malabsorption. The increased enterohepatic cycling of bile acids after cholecystectomy may be responsible for a decrease in their ileal uptake. Very often, as in our patient, the diarrhea precedes cholecystectomy and is considerably increased by it. Cholecystectomy may unmask a previously unrecognized bile acid transport defect. In our patient, this defect might have been caused by the villous atrophy of the terminal ileum.

Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p < 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.