Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

PubMed Central

Wang, Junru; Pathak, Rupak; Garg, Sarita; Hauer-Jensen, Martin

2017-01-01

AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage. PMID:28765691

Low Rectal Cancer Study (MERCURY II)

ClinicalTrials.gov

2016-03-11

Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

The preparation, mincing and canning of bovine offal (ruminal and intestinal wall) for human consumption.

PubMed

van der Made, H N; van Staden, J J

1975-09-01

The results of a sudy of methods of cleaning and preserving bovine ruminal and intestinal wall by canning are described. Such offal could be converted into a hygienically satisfactory and safe food by laboratory washing and canning, and töe end product had a extended shelf life. Methods are described and suggested as a basis for ensuring safe utilisation of a valuable food product.

Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome.

PubMed

Millar-Büchner, Pamela; Philp, Amber R; Gutierrez, Noemí; Villanueva, Sandra; Kerr, Bredford; Flores, Carlos A

2016-12-01

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice. Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples. First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice. In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

Burns, inflammation, and intestinal injury: protective effects of an anti-inflammatory resuscitation strategy.

PubMed

Costantini, Todd W; Peterson, Carrie Y; Kroll, Lauren; Loomis, William H; Putnam, James G; Wolf, Paul; Eliceiri, Brian P; Baird, Andrew; Bansal, Vishal; Coimbra, Raul

2009-12-01

Intestinal barrier breakdown after severe burn can lead to intestinal inflammation, which may act as the source of the systemic inflammatory response. In vitro intestinal cell studies have shown that mitogen-activated protein kinase (MAPK) signaling is an important modulator of intestinal inflammation. We have previously observed that pentoxifylline (PTX) attenuates burn-induced intestinal permeability and tight junction breakdown. We hypothesized that PTX would limit intestinal barrier breakdown and attenuate inflammatory signaling via the MAPK pathway. Male balb/c mice underwent 30% total body surface area full-thickness steam burn. Immediately after burn, animals received an intraperitoneal injection of PTX (12.5 mg/kg) in normal saline or normal saline alone. In vivo intestinal permeability to 4 kDa fluorescein isothiocyanate-dextran was measured. Intestinal extracts were obtained to measure interleukin-6 by enzyme-linked immunosorbent assay, and phosphorylated p38 MAPK, p38 MAPK, phosphorylated extracellular signal-related kinase (1/2) (ERK (1/2)), and ERK (1/2) by immunoblotting. Acute lung injury was assessed by histology at 24 hours after burn. Administration of PTX immediately after injury attenuated burn-induced intestinal permeability. PTX also decreased the burn-induced phosphorylation of p38 MAPK and decreased phosphorylation of ERK (1/2) at 2 hours and 24 hours after injury. Animals given PTX had decreased intestinal interleukin-6 levels. A single dose of PTX also decreased histologic lung injury at 24 hours after burn. PTX attenuates burn-induced intestinal permeability and subsequent intestinal inflammation. Use of PTX after burn was also associated with decreased acute lung injury. Because of its compelling anti-inflammatory effects, PTX may be an ideal candidate for use as an immunomodulatory adjunct to resuscitation fluid.

Bacterial Population in Intestines of Litopenaeus vannamei Fed Different Probiotics or Probiotic Supernatant.

PubMed

Sha, Yujie; Liu, Mei; Wang, Baojie; Jiang, Keyong; Qi, Cancan; Wang, Lei

2016-10-28

The interactions of microbiota in the gut play an important role in promoting or maintaining the health of hosts. In this study, in order to investigate and compare the effects of dietary supplementation with Lactobacillus pentosus HC-2 (HC-2), Enterococcus faecium NRW-2, or the bacteria-free supernatant of a HC-2 culture on the bacterial composition of Litopenaeus vannamei , Illumina sequencing of the V1-V2 region of the 16S rRNA gene was used. The results showed that unique species exclusively existed in specific dietary groups, and the abundance of Actinobacteria was significantly increased in the intestinal bacterial community of shrimp fed with the bacteria-free supernatant of an HC-2 culture compared with the control. In addition, the histology of intestines of the shrimp from the four dietary groups was also described, but no obvious improvements in the intestinal histology were observed. The findings in this work will help to promote the understanding of the roles of intestinal bacteria in shrimps when fed with probiotics or probiotic supernatant.

Dextran sulphate sodium (DSS) causes intestinal histopathology and inflammatory changes consistent with increased gut leakiness in chickens.

PubMed

Zou, X; Ji, J; Wang, J; Qu, H; Shu, D M; Guo, F Y; Luo, C L

2018-04-01

1. The clinical severity, histological changes, indicators of gut leakiness and inflammatory cytokine profiles were studied in chickens with dextran sulphate sodium (DSS)-induced intestinal inflammation. 2. The experimental groups (1.25%, 1.5% and 2.5% DSS) showed clinical signs, such as loose stools and weight loss, which increased with additional treatment days and, as expected, the effects of DSS-induced intestinal inflammation were time and dose-dependent. 3. After 10 d, histological manifestations were evident, including goblet cell depletion, mucus layer loss, significantly shorter villi and a thinner total ileal mucosa. 4. The d(-)-lactate value, which was used as a gut leakiness indicator, was significantly increased in the 2.5% DSS group. 5. Expression of the inflammatory cytokines interleukin-1Beta, tumour necrosis factor alpha and interleukin-10 in the serum significantly increased with DSS treatment. 6. This study indicates that the experimental intestinal inflammation induced by DSS is an ideal model to study the pathogenic mechanisms of intestinal inflammation in chickens and to test the efficacy of therapies.

Histopathologic and molecular evaluation of the Organ Procurement and Transplantation Network selection criteria for intestinal graft donation.

PubMed

Roskott, Anne Margot C; van Haaften, Wouter T; Leuvenink, Henri G D; Ploeg, Rutger J; van Goor, Harry; Blokzijl, Tjasso; Ottens, Petra J; Dijkstra, Gerard; Nieuwenhuijs, Vincent B

2014-06-01

The Organ Procurement and Transplantation Network (OPTN) has formulated criteria for the selection of donors for intestinal transplantation. To date, however, no study has correlated histologic findings of intestinal injury with the OPTN criteria. We aimed to describe histopathologic and molecular features of allograft injury in relation to donor conditions defined by the OPTN criteria. Graft histology (Park Score), Claudin-3 staining, systemic inflammatory markers (C-reactive protein/lipopolysaccharide-binding protein) and expression of heat shock protein 70, heme oxygenase 1, and interleukin 6 were evaluated in multiorgan deceased donors (donation after brain death [DBD] and donation after cardiac death [DCD]). Ninety-seven samples (52 jejunum/45 ileum) were recovered from 59 donors (46 DBD/13 DCD). The OPTN criterion cold ischemia time correlated with histologic injury (Park score) to which the jejunum appeared more susceptible than the ileum. Claudin-3 staining was higher, and heat shock protein 70 expression lower in donors meeting the OPTN criteria compared with donors not meeting the criteria and in DBD versus DCD. In DBD donors, interleukin 6 expression was higher compared with DCD donors and inversely related to C-reactive protein. Our multiparameter analysis suggests that the OPTN criteria can be discriminative concerning intestinal graft quality. Our data suggest that DCD intestinal allografts are qualitatively inferior and that the jejunum is more sensitive to ischemia than the ileum. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

PubMed

Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

2017-02-01

Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

Is endoscopic nodular gastritis associated with premalignant lesions?

PubMed

Niknam, R; Manafi, A; Maghbool, M; Kouhpayeh, A; Mahmoudi, L

2015-06-01

Nodularity on the gastric mucosa is occasionally seen in general practice. There is no consensus about the association of nodular gastritis and histological premalignant lesions. This study is designed to investigate the prevalence of histological premalignant lesions in dyspeptic patients with endoscopic nodular gastritis. Consecutive patients with endoscopic nodular gastritis were compared with an age- and sex-matched control group. Endoscopic nodular gastritis was defined as a miliary nodular appearance of the gastric mucosa on endoscopy. Biopsy samples of stomach tissue were examined for the presence of atrophic gastritis, intestinal metaplasia, and dysplasia. The presence of Helicobacter pylori infection was determined by histology. From 5366 evaluated patients, a total of 273 patients with endoscopic nodular gastritis and 1103 participants as control group were enrolled. H. pylori infection was detected in 87.5% of the patients with endoscopic nodular gastritis, whereas 73.8% of the control group were positive for H. pylori (p < 0.001). Prevalence of incomplete intestinal metaplasia (p = 0.016) and dysplasia (p < 0.001) in patients with endoscopic nodular gastritis were significantly higher than in the control group. Prevalence of atrophic gastritis and complete intestinal metaplasia were also more frequent in patients with endoscopic nodular gastritis than in the control group. Dysplasia, incomplete intestinal metaplasia and H. pylori infection are significantly more frequent in patients with endoscopic nodular gastritis. Although further studies are needed before a clear conclusion can be reached, we suggest that endoscopic nodular gastritis might serve as a premalignant lesion and could be biopsied in all patients for the possibility of histological premalignancy, in addition to H. pylori infection.

Effects of Gum acacia aqueous extract on the histology of the intestine and enzymes of both the intestine and the pancreas of albino rats treated with Meloxicam

PubMed Central

Abd El-Mawla, Ahmed M. A.; Osman, Husam Eldien H.

2011-01-01

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract, in addition to their undesirable side effects on the pancreas. Meloxicam like all NSAIDs has damaging effects on the gastrointestinal tract including perforations, ulcers and bleeding. Objective: The present work describes the effects of Gum acacia aqueous extract on the histology of intestine and enzymes of both intestine and Pancreas of albino rats treated with Meloxicam. Materials and Methods: This study was performed on four groups of equally weighed male rats, each group included ten animals; the first group was received a diet containing 0.2 mg/kg bw meloxicam per day; the second was given 1gm Gum acacia per day in its diet; the third was given meloxicam followed by gum in the same doses per day; while the fourth group (control rats) was placed on a normal diet and water. All rats were received their diet for a period of 21 days. Results: A considerable protective effect of Gum acacia aqueous extract on the histology of intestine of albino rats treated with meloxicam was recorded. In addition, the study displayed a significant increase (P < 0.001) in the intestinal enzymes; lipase, amylase, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in the 1st and 3rd groups animals while these enzymes were significantly decreased (P < 0.001) in the 2nd group when compared with the 4th control group. Conclusion: This study concluded that Gum acacia provides a protection and defense against the harmful effects of meloxicam therapy used as one of the novel anti-Cox-1 and Cox-2 NSAIDs. PMID:21772755

Effects of Gum acacia aqueous extract on the histology of the intestine and enzymes of both the intestine and the pancreas of albino rats treated with Meloxicam.

PubMed

Abd El-Mawla, Ahmed M A; Osman, Husam Eldien H

2011-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract, in addition to their undesirable side effects on the pancreas. Meloxicam like all NSAIDs has damaging effects on the gastrointestinal tract including perforations, ulcers and bleeding. The present work describes the effects of Gum acacia aqueous extract on the histology of intestine and enzymes of both intestine and Pancreas of albino rats treated with Meloxicam. This study was performed on four groups of equally weighed male rats, each group included ten animals; the first group was received a diet containing 0.2 mg/kg bw meloxicam per day; the second was given 1gm Gum acacia per day in its diet; the third was given meloxicam followed by gum in the same doses per day; while the fourth group (control rats) was placed on a normal diet and water. All rats were received their diet for a period of 21 days. A considerable protective effect of Gum acacia aqueous extract on the histology of intestine of albino rats treated with meloxicam was recorded. In addition, the study displayed a significant increase (P < 0.001) in the intestinal enzymes; lipase, amylase, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in the 1(st) and 3(rd) groups animals while these enzymes were significantly decreased (P < 0.001) in the 2(nd) group when compared with the 4(th) control group. This study concluded that Gum acacia provides a protection and defense against the harmful effects of meloxicam therapy used as one of the novel anti-Cox-1 and Cox-2 NSAIDs.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome.

PubMed

Suri, Megha; Turner, Justine M; Sigalet, David L; Wizzard, Pamela R; Nation, Patrick N; Ball, Ron O; Pencharz, Paul B; Brubaker, Patricia L; Wales, Paul W

2014-10-01

Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS. In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC). Parenteral nutrition (PN) commenced on day 1 and was weaned as enteral nutrition (EN) advanced. IV GLP-2 (11 nmol/kg/d) or saline was initiated on day 2. Piglets were maintained for 14 d. Clinical, functional, morphological, and histological outcomes were obtained. JC-GLP-2 piglets had fewer days on PN (10.0 ± 0.6 vs. 13.8 ± 0.2), more days on EN (4.0 ± 0.6 vs. 0.2 ± 0.2), a higher percentage of EN at termination (92 ± 5 vs. 52 ± 10%), fewer days of diarrhea (8.0 ± 0.7 vs. 12.3 ± 0.4), increased intestinal length (19 ± 4 vs. -5 ± 3%), and deeper jejunal crypts (248 ± 21 vs. 172 ± 12 μm), compared with saline piglets. GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

Natural history of experimental intestinal atresia: morphologic and ultrastructural study.

PubMed

Baglaj, S M; Czernik, J; Kuryszko, J; Kuropka, P

2001-09-01

The aim of this study was to evaluate a natural history of congenital intestinal atresia (IA) in the chick embryo and to assess the type and nature of changes in the intestine at various developmental stages. Chick embryos underwent operative induction of IA on the 12th day of incubation. The procedure consisted of electrocoagulation of the mesenteric vessels supplying a 7- to 8-mm intestinal segment. The embryos were subjected to macroscopic examination, histologic and ultrastructural studies of the preatretic and postatretic bowel using the light microscope, scanning, and transmission electron microscopes. All investigations were performed in an experimental group (operated embryos), in a control group, and in a sham-operated group on the 15th, 17th, 19th, and 21st day of incubation. The original technique of an iatrogenic "vascular event" proved to be effective because IA developed in 96% of embryos surviving the procedure. The affected portion of the bowel underwent progressive necrosis, and signs of bowel obstruction could be observed 48 hours after operation. Cord atresia (type II) developed in 81% of embryos. Histologic investigations showed progressive thinning of mucosa, flattening of mucosal folds, and epithelial detachment within the intestine proximal to atresia. There was only mild hypertrophy of the muscular layers. All these pathomorphologic changes were of rapidly progressive nature until the 17th day of incubation. Later, the rate of distension of preatretic bowel and histologic changes were less. Ultrastructural investigation of the proximal bowel showed progressive flattening of the enterocytes associated with their apical bulging, widening of the intercellular spaces, and microvilli atrophy. Surprisingly, at days 19 and 21 of incubation, signs of induction of adaptive mechanisms with partial restoration of near-normal microvilli pattern were observed. Study of natural history of experimental IA indicates that histologic and ultrastructural lesions of the bowel are of dynamic nature and are not only the effect of pathologic intraluminal pressure. Copyright 2001 by W.B. Saunders Company.

OLGA- and OLGIM-based staging of gastritis using narrow-band imaging magnifying endoscopy.

PubMed

Saka, Akiko; Yagi, Kazuyoshi; Nimura, Satoshi

2015-11-01

As atrophic gastritis and intestinal metaplasia as a result of Helicobacter pylori are considered risk factors for gastric cancer, it is important to assess their severity. In the West, the operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging systems based on biopsy have been widely adopted. In Japan, however, narrow-band imaging (NBI)-magnifying endoscopic diagnosis of gastric mucosal inflammation, atrophy, and intestinal metaplasia has been reported to be fairly accurate. Therefore, we investigated the practicality of NBI-magnifying endoscopy (NBI-ME) for gastritis staging. We enrolled 55 patients, in whom NBI-ME was used to score the lesser curvature of the antrum (antrum) and the lesser curvature of the lower body (corpus). The NBI-ME score classification was established from images obtained beforehand, and then biopsy specimens taken from the observed areas were scored according to histological findings. The NBI-ME and histology scores were then compared. Furthermore, we assessed the NBI-ME and histology stages using a combination of scores for the antrum and corpus, and divided the stages into two risk groups: low and high. The degree to which the stage assessed by NBI-ME approximated that assessed by histology was then ascertained. Degree of correspondence between the NBI-ME and histology scores was 69.1% for the antrum and 72.7% for the corpus, and that between the high- and low-risk groups was 89.1%. Staging of gastritis using NBI-ME approximates that based on histology, and would be a practical alternative to the latter. © 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

PubMed

Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

2009-09-18

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.

Optimum Timing for Surgery After Pre-operative Radiotherapy 6 vs 12 Weeks

ClinicalTrials.gov

2015-06-22

Adenocarcinoma of the Rectum; Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Digestibility of soybean and pigeon pea seed meals and morphological intestinal alterations in pigs.

PubMed

Mekbungwan, Apichai; Thongwittaya, Narin; Yamauchi, Koh-En

2004-06-01

To compare the nutrient digestibility of soybean meal (SM) and pigeon pea seed meal (PM) as well as morphological intestinal alterations in piglets fed them, three pigs per group were randomly selected at the end of the feeding experiment for ten days. Growth performance was higher in the SM group than in the PM group (p<0.05). The digestibility of crude protein, crude fat and crude fiber was 80.6%, 23.6% and 52.4% in the SM group, while in the PM group, values of 49.8%, 23.6% and 43.2% were observed, respectively. Digestible energy was 3.26 kcal g(-1) in SM and 3.17 kcal g(-1) in PM. It was concluded that the digestibility of PM was lower than that of SM; almost half of the protein in PM was digested. Dietary treatments had no effect on length of each small intestinal segment and weight of visceral organs (small intestine, liver, heart, spleen, kidney, stomach and lung) except the decreased kidney weight in the PM group (p<0.05). The epithelial cells on the jejunal villi showed a dome-like shape in the SM group, but they were a flat shape in the PM group. The present digestion trial and histological intestinal data suggest that the intestinal digestive and absorptive functions are much more atrophied in the PM group than in the SM group, and demonstrate that histological intestinal alterations might be well related with the intestinal functions.

Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma.

PubMed

Kim, Su Mi; Min, Byung Hoon; Lee, Jeeyun; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Jae J; Kang, Won Ki; Kim, Sung; Choi, Min Gew

2018-01-01

Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification. We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group. In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women. These findings support that female sex hormones might be protective against intestinal-type gastric cancer. © Copyright: Yonsei University College of Medicine 2018

Small intestinal function and dietary status in dermatitis herpetiformis.

PubMed Central

Gawkrodger, D J; McDonald, C; O'Mahony, S; Ferguson, A

1991-01-01

Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal. PMID:2026337

Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells

PubMed Central

Moorefield, Emily C.; Andres, Sarah F.; Blue, R. Eric; Van Landeghem, Laurianne; Mah, Amanda T.; Santoro, M. Agostina; Ding, Shengli

2017-01-01

Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFPLow), activatable reserve IESC and enteroendocrine cells (Sox9-EGFPHigh), Sox9-EGFPSublow progenitors, and Sox9-EGFPNegative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFPLow IESC and Sox9-EGFPHigh cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging. PMID:28854151

Ulcerative enteritis in Homarus americanus: case report and molecular characterization of intestinal aerobic bacteria of apparently healthy lobsters in live storage.

PubMed

Battison, Andrea L; Després, Béatrice M; Greenwood, Spencer J

2008-10-01

An intermoult male American lobster, Homarus americanus, with severe intestinal lesions was encountered while collecting samples of aerobic intestinal bacteria from lobsters held in an artificial sea-water recirculation aquarium system. Grossly, the intestine was firm, thickened, and white. Histologic examination revealed a severe, diffuse, ulcerative enteritis which spared the chitin-lined colon, somewhat similar to hemocytic enteritis of shrimp. The bacterial isolates from this lobster were compared to 11 other lobsters lacking gross intestinal lesions. Two organisms, one identified as Vibrio sp. and another most similar to an uncultured proteobacterium (98.9%), clustering with Rhanella and Serratia species using 16S rDNA PCR, were isolated from the intestines of the 11, grossly normal, lobsters and the affected lobster. An additional two intestinal isolates were cultured only from the lobster with ulcerative enteritis. One, a Flavobacterium, similar to Lutibacter litoralis (99.3%), possibly represented a previously described commensal of the distal intestine. The second, a Vibrio sp., was unique to the affected animal. While the etiology of the ulcerative enteritis remains undetermined, this report represents the first description of gross and histologic findings in H. americanus of a condition which has morphologic similarities to hemocytic enteritis of shrimp. An additional observation was a decrease in the number of intestinal isolates recovered from the 11 apparently healthy lobsters compared to that previously reported for recently harvested lobster. More comprehensive studies of the relationship between the health of lobsters, gut microbial flora and the husbandry and environment maintained within holding units are warranted.

Division of Chinese soft-shelled turtle intestine with molecular markers is slightly different from the morphological and histological observation.

PubMed

Zhang, Zuobing; Song, Ruxin; Xing, Xiao; Wang, Lan; Niu, Cuijuan

2018-01-01

The Chinese soft-shelled turtle (Pelodiscus sinensis) is a commercially important species in Asian countries. Knowledge of its nutritional requirements and physiology is essential for determining the appropriate content of the feed for this animal. However, the lack of functional characterization of the intestine of this turtle limits the understanding of its absorption and utilization of nutritional materials. To solve this problem, this work utilized anatomical and histological methods to characterize 9 segments sampled along the anterior-posterior axis of the intestine. Furthermore, 9 genes, which have been well documented in the intestine division of mammals and fish, were employed to functionally characterize the 9 sampled segments. Our results suggest that regions covering from the starting site to S3 (position at 29.9% of the total length from the starting of the intestine) are the equivalent of mammalian dedumonen, and those covering S4 (40.2%) and S5 (65.4%), posterior to S8 (92.7%), are the equivalent of the mammalian ileum and the large intestine, respectively. As to the region spaning S6 (81.3%) and S7 (87.3%), its functional equivalent (small intestine or large intestine) may be variable and depends on the functional genes. This molecular characterization in relation to the division of the intestine of Chinese soft-shelled turtle may contribute to the understanding of the nutritional physiology of the turtle, and promote Chinese soft-shelled turtle production. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial

ClinicalTrials.gov

2017-03-08

Adenocarcinoma; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

PubMed

Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

2013-12-01

DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

Apelin targets gut contraction to control glucose metabolism via the brain

PubMed Central

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-01-01

Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. PMID:26565000

Alteration of histological gastritis after cure of Helicobacter pylori infection.

PubMed

Hojo, M; Miwa, H; Ohkusa, T; Ohkura, R; Kurosawa, A; Sato, N

2002-11-01

It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. To clarify the histological changes after the cure of H. pylori infection through a literature survey. Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

Histologic recovery among children with celiac disease on a gluten-free diet. A long-term follow-up single-center experience.

PubMed

Belei, Oana; Dobrescu, Andreea; Heredea, Rodica; Iacob, Emil Radu; David, Vlad; Marginean, Otilia

2018-01-01

Celiac disease (CD) is defined by gluten-induced immune-mediated enteropathy, affecting approximately 1% of the genetically predisposed population. The immunologic response to gluten causes characteristic intestinal alterations with gradual development. Histologic recovery of intestinal architecture was reported to occur within 6-12 months after starting a gluten-free diet, simultaneously with clinical remission. The aim of this study was to assess the rate and timing of histologic recovery among children with CD on a gluten-free diet, diagnosed and followed in an academic referral pediatric center during a 10-year period. 105 biopsy-confirmed CD children underwent follow-up small intestinal biopsies within at least 1 year after dietary gluten withdrawal. Further biopsies were performed if villous alterations were persistent. The Marsh classification modified by Oberhuber was used to score the histologic injuries. In all 19 cases with Marsh type II at diagnosis, villous alterations normalized to Marsh type 0 within the first year. From 86 children enrolled with Marsh type III lesions, histologic remission was observed in 81.4% after 1 year, 91.8% within 2-3 years and 97.6% in long-term follow up (≥ 3 years). Two (2.3%) patients with concomitant selective IgA deficiency had symptoms of malabsorption and persisting villous atrophy lasting more than 3 years despite a gluten-free diet. There was a significant statistic difference between the proportion of children with Marsh type IIIA, type IIIB and Marsh type IIIC respectively that achieved histologic recovery within 1 to 2 years after gluten withdrawal. There were more children with partial 25 (92.6%) and subtotal villous atrophy 30 (88.2%) showing histologic improvement, compared to only 15 (60%) patients with total villous atrophy that recovered within the first 2 years of diet ( p = 0.01 and p = 0.02 respectively). Histologic recovery in CD after starting a gluten-free diet in children takes at least 1 year and might be incomplete only in a small proportion of children, mainly associated with IgA immunodeficiency. Systematic follow-up of children with CD and persistent malabsorption syndrome is needed in order to avoid secondary complications.

A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.

PubMed

Khayyal, Mohamed T; Abdel-Naby, Doaa H; Abdel-Aziz, Heba; El-Ghazaly, Mona A

2014-09-25

Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

Exploring new technologies to facilitate laparoscopic surgery: creating intestinal anastomoses without sutures or staples, using a radio-frequency-energy-driven bipolar fusion device.

PubMed

Smulders, J F; de Hingh, I H J T; Stavast, J; Jackimowicz, J J

2007-11-01

Intestinal anastomotic healing requires apposition of the collagen containing submucosal layers of the opposing intestinal walls, which is traditionally achieved by staples or sutures. Recently, a feedback-controlled bipolar sealing system (LigaSure) has been successfully introduced to seal and transect vessels. Since this technology depends on fusion of collagen fibres which are abundantly present in the intestinal wall, the possibility to create intestinal anastomoses using this technology was investigated in the present study. For this purpose a new-generation radiofrequency (RF) generator and a prototype of the Ligasure Anastomotic Device (LAD) have been developed. The generator incorporates a closed loop control system which monitors tissue fusion, compares it with a mathematical model of ideal fusion based on the density and compliance of intestinal tissue and adjusts energy output accordingly. In total 8 anastomoses were created in a porcine model (4 pigs, 2 anastomoses each) and healing was assessed by macroscopic and histological examination. All seals were macroscopic intact both immediate after creation and at sacrifice at the 7th postoperative day. Between operations, pigs appeared healthy and had normal intestinal passage. Histological examination of the anastomoses revealed undisturbed healing with granulation tissue, newly synthesised collagen in the submucosa and re-epithelialization at the borders of the seals. These results confirm the feasibility to create experimental intestinal anastomoses using LigaSure technology. This may be an important step towards the development of new laparoscopic equipment combining dissecting and reconstructive properties within one single instrument.

Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

PubMed

Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

2016-11-01

Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine-supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

[Postconditioning -- effective method against distant organ dysfunction?].

PubMed

Onody, Péter; Rosero, Olivér; Kovács, Tibor; Garbaisz, Dávid; Hegedüs, Viktor; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2012-08-01

The ischemia-reperfusion injury of the small intestine is a condition of high mortality, which occurs following superior mesenteric artery (SMA) embolization or circulatory redistribution. The aim of the study was to evaluate the local and systemic effects of postconditioning in a rat model of small intestine ischemia-reperfusion. Male Wistar rats underwent 60 min ischemia by the clamping of the SMA, followed by 6 hrs of reperfusion. The animals (n = 30) were randomized into three groups: sham-operated, control-, and postconditioned. Postconditioning was performed at the very onset of reperfusion by 6 alternating cycles of 10-10 seconds reperfusion/reocclusion, for a total of 2 min. At the end of the reperfusion blood and tissue (small intestine, lungs, kidney, liver) samples were taken for histological examination. The antioxidant status of small intestine was measured from intestinal homogenates. Histologic results revealed increased damage in control-group lungs, kidney, liver and small intestine in comparison with the postconditioned group. The injury was supported by significantly higher wet/dry weight ratio (p = 0.026), and serum levels of creatinine (p = 0.013), ASAT (p = 0.038), LDH (p = 0.028) and CK (p = 0.038) in the control group. The postconditioned group showed lower serum IL-6 levels (420 pg/ml vs. 188 pg/ml), as well as significantly higher mucosal antioxidant concentration. Postconditioning was able to decrease not only local, but the systemic damage intensity also, after a small intestinal ischemic-reperfusion episode.

Anti-inflammatory and Antioxidant Effects of Flavonoid-Rich Fraction of Bergamot Juice (BJe) in a Mouse Model of Intestinal Ischemia/Reperfusion Injury

PubMed Central

Impellizzeri, Daniela; Cordaro, Marika; Campolo, Michela; Gugliandolo, Enrico; Esposito, Emanuela; Benedetto, Filippo; Cuzzocrea, Salvatore; Navarra, Michele

2016-01-01

The flavonoid-rich fraction of bergamot juice (BJe) has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R) injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-κB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury. PMID:27471464

Anti-inflammatory and Antioxidant Effects of Flavonoid-Rich Fraction of Bergamot Juice (BJe) in a Mouse Model of Intestinal Ischemia/Reperfusion Injury.

PubMed

Impellizzeri, Daniela; Cordaro, Marika; Campolo, Michela; Gugliandolo, Enrico; Esposito, Emanuela; Benedetto, Filippo; Cuzzocrea, Salvatore; Navarra, Michele

2016-01-01

The flavonoid-rich fraction of bergamot juice (BJe) has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R) injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-κB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury.

Human mesenchymal stromal cells decrease mortality after intestinal ischemia and reperfusion injury.

PubMed

Markel, Troy A; Crafts, Trevor D; Jensen, Amanda R; Hunsberger, Erin Bailey; Yoder, Mervin C

2015-11-01

Cellular therapy is a novel treatment option for intestinal ischemia. Bone marrow-derived mesenchymal stromal cells (BMSCs) have previously been shown to abate the damage caused by intestinal ischemia/reperfusion (I/R) injury. We therefore hypothesized that (1) human BMSCs (hBMSCs) would produce more beneficial growth factors and lower levels of proinflammatory mediators compared to differentiated cells, (2) direct application of hBMSCs to ischemic intestine would decrease mortality after injury, and (3) decreased mortality would be associated with an altered intestinal and hepatic inflammatory response. Adult hBMSCs and keratinocytes were cultured on polystyrene flasks. For in vitro experiments, cells were exposed to tumor necrosis factor, lipopolysaccharides, or 2% oxygen for 24 h. Supernatants were then analyzed for growth factors and chemokines by multiplex assay. For in vivo experiments, 8- to 12-wk-old male C57Bl6J mice were anesthetized and underwent a midline laparotomy. Experimental groups were exposed to temporary superior mesenteric artery occlusion for 60 min. Immediately after ischemia, 2 × 10(6) hBMSCs or keratinocytes in phosphate-buffered saline were placed into the peritoneal cavity. Animals were then closed and allowed to recover for 6 h (molecular/histologic analysis) or 7 d (survival analysis). After 6-h reperfusion, animals were euthanized. Intestines and livers were harvested and analyzed for inflammatory chemokines, growth factors, and histologic changes. hBMSCs expressed higher levels of human interleukin (IL) 6, IL-8, vascular endothelial growth factor (VEGF), and epidermal growth factor and lower levels of IL-1, IL-3, IL-7, and granulocyte-monocyte colony-stimulating factor after stimulation. In vivo, I/R resulted in significant mortality (70% mortality), whereas application of hBMSCs after ischemia decreased mortality to 10% in a dose-dependent fashion (P = 0.004). Keratinocyte therapy offered no improvements in mortality above I/R. Histologic profiles were equivalent between ischemic groups, regardless of the application of hBMSCs or keratinocytes. Cellular therapy yielded significantly decreased murine intestinal levels of soluble activin receptor-like kinase 1, betacellulin, and endothelin, whereas increasing levels of eotaxin, monokine induced by gamma interferon (MIG), monocyte chemoattractant protein 1, IL-6, granulocyte colony-stimulating factor (G-CSF), and interferon gamma-induced protein 10 (IP-10) from ischemia were appreciated. hBMSC therapy yielded significantly higher expression of murine intestinal VEGF and lower levels of intestinal MIG compared to keratinocyte therapy. Application of hBMSCs after ischemia yielded significantly lower murine levels of hepatic MIG, IP-10, and G-CSF compared to keratinocyte therapy. Human BMSCs produce multiple beneficial growth factors. Direct application of hBMSCs to the peritoneal cavity after intestinal I/R decreased mortality by 60%. Improved outcomes with hBMSC therapy were not associated with improved histologic profiles in this model. hBMSC therapy was associated with higher VEGF in intestines and lower levels of proinflammtory MIG, IP-10, and G-CSF in liver tissue after ischemia, suggesting that reperfusion with hBMSC therapy may alter survival by modulating the systemic inflammatory response to ischemia. Copyright © 2015 Elsevier Inc. All rights reserved.

Distinguishing Intestinal Lymphoma From Inflammatory Bowel Disease in Canine Duodenal Endoscopic Biopsy Samples.

PubMed

Carrasco, V; Rodríguez-Bertos, A; Rodríguez-Franco, F; Wise, A G; Maes, R; Mullaney, T; Kiupel, M

2015-07-01

Inflammatory bowel disease (IBD) and intestinal lymphoma are intestinal disorders in dogs, both causing similar chronic digestive signs, although with a different prognosis and different treatment requirements. Differentiation between these 2 conditions is based on histopathologic evaluation of intestinal biopsies. However, an accurate diagnosis is often difficult based on histology alone, especially when only endoscopic biopsies are available to differentiate IBD from enteropathy-associated T-cell lymphoma (EATL) type 2, a small cell lymphoma. The purpose of this study was to evaluate the utility of histopathology; immunohistochemistry (IHC) for CD3, CD20, and Ki-67; and polymerase chain reaction (PCR) for antigen receptor rearrangement (T-cell clonality) in the differential diagnosis of severe IBD vs intestinal lymphoma. Endoscopic biopsies from 32 dogs with severe IBD or intestinal lymphoma were evaluated. The original diagnosis was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone followed by a second evaluation using morphology in association with IHC for CD3 and CD20 and a third evaluation using PCR for clonality. Our results show that, in contrast to feline intestinal lymphomas, 6 of 8 canine small intestinal lymphomas were EATL type 1 (large cell) lymphomas. EATL type 2 was uncommon. Regardless, in dogs, intraepithelial lymphocytes were not an important diagnostic feature to differentiate IBD from EATL as confirmed by PCR. EATL type 1 had a significantly higher Ki-67 index than did EATL type 2 or IBD cases. Based on the results of this study, a stepwise diagnostic approach using histology as the first step, followed by immunophenotyping and determining the Ki67 index and finally PCR for clonality, improves the accuracy of distinguishing intestinal lymphoma from IBD in dogs. © The Author(s) 2014.

Early-life dietary spray-dried plasma influences immunological and intestinal injury responses to later-life Salmonella typhimurium challenge.

PubMed

Boyer, P E; D'Costa, S; Edwards, L L; Milloway, M; Susick, E; Borst, L B; Thakur, S; Campbell, J M; Crenshaw, J D; Polo, J; Moeser, A J

2015-03-14

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 10⁹ colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells.

PubMed

Moorefield, Emily C; Andres, Sarah F; Blue, R Eric; Van Landeghem, Laurianne; Mah, Amanda T; Santoro, M Agostina; Ding, Shengli

2017-08-29

Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP Low ), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP High ), Sox9-EGFP Sublow progenitors, and Sox9-EGFP Negative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFP Low IESC and Sox9-EGFP High cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging.

Small bowel dilation in children with short bowel syndrome is associated with mucosal damage, bowel-derived bloodstream infections, and hepatic injury.

PubMed

Hukkinen, Maria; Mutanen, Annika; Pakarinen, Mikko P

2017-09-01

Liver disease occurs frequently in short bowel syndrome. Whether small bowel dilation in short bowel syndrome could influence the risk of liver injury through increased bacterial translocation remains unknown. Our aim was to analyze associations between small bowel dilation, mucosal damage, bloodstream infections, and liver injury in short bowel syndrome patients. Among short bowel syndrome children (n = 50), maximal small bowel diameter was measured in contrast series and expressed as the ratio to the height of the fifth lumbar vertebra (small bowel diameter ratio), and correlated retrospectively to fecal calprotectin and plasma citrulline-respective markers of mucosal inflammation and mass-bloodstream infections, liver biochemistry, and liver histology. Patients with pathologic small bowel diameter ratio >2.17 had increased fecal calprotectin and decreased citrulline (P < .04 each). Of 33 bloodstream infections observed during treatment with parenteral nutrition, 16 were caused by intestinal bacteria, cultured 15 times more frequently when small bowel diameter ratio was >2.17 (P < .001). Intestinal bloodstream infections were predicted by small bowel diameter ratio (odds ratio 1.88, P = .017), and their frequency decreased after operative tapering procedures (P = .041). Plasma bilirubin concentration, gamma-glutamyl transferase activity, and histologic grade of cholestasis correlated with small bowel diameter ratio (0.356-0.534, P < .014 each), and were greater in the presence of intestinal bloodstream infections (P < .001 for all). Bloodstream infections associated with portal inflammation, cholestasis, and fibrosis grades (P < .031 for each). In linear regression, histologic cholestasis was predicted by intestinal bloodstream infections, small bowel diameter ratio, and parenteral nutrition (β = 0.36-1.29; P < .014 each), while portal inflammation by intestinal bloodstream infections only (β = 0.62; P = .033). In children with short bowel syndrome, small bowel dilation correlates with mucosal damage, bloodstream infections of intestinal origin, and cholestatic liver injury. In addition to parenteral nutrition, small bowel dilation and intestinal bloodstream infections contribute to development of short bowel syndrome-associated liver disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Present Status of Subclinical Intestinal Malabsorption in the Tropics

PubMed Central

Falaiye, J. M.

1971-01-01

A review of the literature on subclinical intestinal disease shows its probable relevance in certain nutritional deficiencies in the indigenous residents of tropical climates. A significant incidence of intestinal disease has been defined among asymptomatic fit-looking adult Nigerians. The results of subsequent investigation into the pathogenesis of this disorder strongly point to hypoalbuminaemia as the important factor capable of producing a biochemically and histologically defined malabsorptive state leading to subnormal nutritional status among members of this community. ImagesFIG. 3 PMID:5125280

Rapid protein disappearance rates along the small intestine advantage poultry performance and influence the post-enteral availability of amino acids.

PubMed

Truong, Ha H; Chrystal, Peter V; Moss, Amy F; Selle, Peter H; Liu, Sonia Yun

2017-12-01

A foundation diet, an intermediate blend and a summit diet were formulated with different levels of soyabean meal, casein and crystalline amino acids to compare 'slow' and 'rapid' protein diets. The diets were offered to male Ross 308 chicks from 7 to 28 d post-hatch and assessed parameters included growth performance, nutrient utilisation, apparent digestibility coefficients and disappearance rates of starch and protein (N) in four small intestinal segments. Digestibility coefficients and disappearance rates of sixteen amino acids in three small intestinal segments and amino acid concentrations in plasma from portal and systemic circulations from the foundation and summit diets were determined. The dietary transition significantly accelerated protein (N) disappearance rates in the distal jejunum and ileum. The transition from foundation to summit diets significantly increased starch digestibility coefficients in the ileum and disappearance rates in all four small intestinal segments. These starch responses were associated with significant enhancements in nutrient utilisation. The dietary transition linearly increased digestibility coefficients and disappearance rates of amino acids in the majority of cases. The summit diet increased plasma concentrations of five amino acids but decreased those of four amino acids relative to the foundation diet to significant extents. Plasma concentrations of free amino acids were higher in the portal than systemic circulations. Rapid protein disappearance rates advantaged poultry performance and influenced post-enteral availability of amino acids. If the underlying mechanisms are to be identified, further research into the impact of protein digestive dynamics on broiler performance is required but appears justified.

Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

PubMed

Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

2016-09-01

4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Umbilical mesenchymal stromal cells provide intestinal protection through nitric oxide dependent pathways.

PubMed

Jensen, Amanda R; Drucker, Natalie A; Ferkowicz, Michael J; Markel, Troy A

2018-04-01

Umbilical-derived mesenchymal stromal cells (USCs) have shown promise in the protection of ischemic organs. We hypothesized that USCs would improve mesenteric perfusion, preserve intestinal histological architecture, and limit inflammation by nitric oxide-dependent mechanisms following intestinal ischemia/reperfusion (IR) injury. Adult wild-type C57BL/6J (WT) and endothelial nitric oxide synthase knock out (eNOS KO) mice were used: (1) WT IR + vehicle, (2) WT IR + USC, (3) eNOS KO IR + vehicle, and (4) eNOS KO IR + USC. Mice were anesthetized, and a midline laparotomy was performed. The superior mesenteric artery was clamped with a nonoccluding clamp for 60-min. Following IR, mice were treated with an injection of 250 μL phosphate buffered saline or 2 × 10 6 USCs suspended in 250-μL phosphate buffered saline solution. Mesenteric perfusion images were acquired using laser Doppler imaging. Perfusion was analyzed as a percentage of baseline. At 24 h, mice were euthanized, and intestines were harvested. Intestines were evaluated for injury, and data were analyzed using the Mann-Whitney or Kruskal-Wallis tests. Intestinal mesenteric perfusion was significantly improved in WT mice treated with USC therapy compared with eNOS KOs. Intestinal histological architecture was preserved with USC therapy in WT mice. However, in eNOS KO mice, this benefit was abolished. Finally, the presence of several cytokines and growth factors were significantly improved in WT mice compared with eNOS KO mice treated with USCs. The benefits of USC-mediated therapy following intestinal IR injury likely occur via nitric oxide-dependent pathways. Further studies are required to define the molecular mechanisms by which USCs activate endothelial nitric oxide synthase to bring about their protective effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Apelin targets gut contraction to control glucose metabolism via the brain.

PubMed

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-02-01

The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Loss of Junctional Adhesion Molecule A Promotes Severe Steatohepatitis in Mice on a Diet High in Saturated Fat, Fructose, and Cholesterol.

PubMed

Rahman, Khalidur; Desai, Chirayu; Iyer, Smita S; Thorn, Natalie E; Kumar, Pradeep; Liu, Yunshan; Smith, Tekla; Neish, Andrew S; Li, Hongliang; Tan, Shiyun; Wu, Pengbo; Liu, Xiaoxiong; Yu, Yuanjie; Farris, Alton B; Nusrat, Asma; Parkos, Charles A; Anania, Frank A

2016-10-01

There is evidence from clinical studies that compromised intestinal epithelial permeability contributes to the development of nonalcoholic steatohepatitis (NASH), but the exact mechanisms are not clear. Mice with disruption of the gene (F11r) encoding junctional adhesion molecule A (JAM-A) have defects in intestinal epithelial permeability. We used these mice to study how disruption of the intestinal epithelial barrier contributes to NASH. Male C57BL/6 (control) or F11r(-/-) mice were fed a normal diet or a diet high in saturated fat, fructose, and cholesterol (HFCD) for 8 weeks. Liver and intestinal tissues were collected and analyzed by histology, quantitative reverse-transcription polymerase chain reaction, and flow cytometry. Intestinal epithelial permeability was assessed in mice by measuring permeability to fluorescently labeled dextran. The intestinal microbiota were analyzed using 16S ribosomal RNA sequencing. We also analyzed biopsy specimens from proximal colons of 30 patients with nonalcoholic fatty liver disease (NAFLD) and 19 subjects without NAFLD (controls) undergoing surveillance colonoscopy. F11r(-/-) mice fed a HFCD, but not a normal diet, developed histologic and pathologic features of severe NASH including steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis, whereas control mice fed a HFCD developed only modest steatosis. Interestingly, there were no differences in body weight, ratio of liver weight:body weight, or glucose homeostasis between control and F11r(-/-) mice fed a HFCD. In these mice, liver injury was associated with significant increases in mucosal inflammation, tight junction disruption, and intestinal epithelial permeability to bacterial endotoxins, compared with control mice or F11r(-/-) mice fed a normal diet. The HFCD led to a significant increase in inflammatory microbial taxa in F11r(-/-) mice, compared with control mice. Administration of oral antibiotics or sequestration of bacterial endotoxins with sevelamer hydrochloride reduced mucosal inflammation and restored normal liver histology in F11r(-/-) mice fed a HFCD. Protein and transcript levels of JAM-A were significantly lower in the intestinal mucosa of patients with NAFLD than without NAFLD; decreased expression of JAM-A correlated with increased mucosal inflammation. Mice with defects in intestinal epithelial permeability develop more severe steatohepatitis after a HFCD than control mice, and colon tissues from patients with NAFLD have lower levels of JAM-A and higher levels of inflammation than subjects without NAFLD. These findings indicate that intestinal epithelial barrier function and microbial dysbiosis contribute to the development of NASH. Restoration of intestinal barrier integrity and manipulation of gut microbiota might be developed as therapeutic strategies for patients with NASH. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ginger Extract and [6]-Gingerol Inhibit Contraction of Rat Entire Small Intestine.

PubMed

Chatturong, Usana; Kajsongkram, Tanwarat; Tunsophon, Sakara; Chanasong, Rachanee; Chootip, Krongkarn

2018-01-01

This study aims to investigate the effect of oral administration and the direct action of ginger extract or [6]-gingerol on small intestinal contractility. The direct effect of 10 minutes preincubation of ginger ethanolic extract (10, 100 and 300 μg/mL) or [6]-gingerol (1, 30, and 100 μM) on 0.01 to 30 μM ACh-induced contractions of all parts of the small intestine isolated from normal rats was investigated using the organ bath technique. For in vivo study, the rats were orally administered with extract (10, 20, and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d) for 7 days, followed by determining the contractile responses to ACh of rat isolated duodenum, jejunum, and ileum and their histology were assessed. Direct application of the extract or [6]-gingerol attenuated ACh-induced contractions in each small intestinal segment, E max was reduced by 40% to 80%, while EC 50 increased 3- to 8-fold from control. Similarly, in the in vivo study ACh-induced contractions were reduced in all parts of the small intestine isolated from rats orally treated with ginger extract (20 and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d). E max decreased 15% to 30%, while EC 50 increased 1- to 3-fold compared to control. No discernable changes in the histology of intestinal segments were detectable. Thus, the results support the clinical application of ginger for disorders of gastrointestinal motility.

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

PubMed Central

2014-01-01

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

[Investigation of postconditioning in intestinal ischemia-reperfusion experimental models].

PubMed

Rosero, Olivér; Onody, Péter; Stangl, Rita; Hegedus, Viktor; Lotz, Gábor; Blázovics, Anna; Kupcsulik, Péter; Szijártó, Attila

2011-02-01

The ischemic-reperfusion injury of the intestine, which occurs as a consequence of circulatory redistribution or occlusion of the superior mesenteric artery, is associated with high mortality rates. Postconditioning may reduce ischemic-reperfusion damage in such cases. Effects of this new surgical method were investigated in rats. Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion in four groups: sham-operated, control and two postconditioned groups with different algorithms. Postconditioning was performed immediately at the beginning of reperfusion, by repetitive cycles of reperfusion and reocclusion. 3 cycles of 1 minute and 6 cycles of 10 seconds were applied according to groups. Intestinal microcirculation was followed by laser Doppler flowmetry. Blood and tissue samples were taken after 60 minutes of reperfusion. Histological analayses of the small intestine, measurement of serum necroenzyme levels and IL-6, mesenterial venous blood gas analyses were preformed and antioxidant state of the mucosa was investigated. The microcirculation during the reperfusion showed significant improvement in both postconditioned groups. Histological damage, necroenzyme and IL-6 levels were significantly reduced, while antioxidant state was improved in the postconditioned groups. Postconditioning was capable of increasing the guts chance to survive ischemic-reperfusion injury caused by superior mesenteric artery occlusion.

Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.

PubMed

Albuquerque, Andreia

2014-11-16

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.

Tissue Transglutaminase Levels Are Not Sufficient to Diagnose Celiac Disease in North American Practices Without Intestinal Biopsies.

PubMed

Elitsur, Yoram; Sigman, Terry; Watkins, Runa; Porto, Anthony F; Leonard Puppa, Elaine L; Foglio, Elsie J; Preston, Deborah L

2017-01-01

Celiac serology is crucial for the diagnosis of celiac disease in children. The American guideline for celiac disease in children suggested that positive serology should be followed by confirmatory intestinal histology. The relationship between high tissue transglutaminase titers and celiac disease in children has not been well investigated in children from North America. In the present study, we investigated whether different tissue transglutaminase titers in symptomatic children could predict celiac disease without the confirmation of intestinal histology. Data from biopsy confirmed celiac children were collected from four different clinics in North America. Clinical, serological, histological, and follow-up data were collected. The accuracy rates of various tissue transglutaminase titers to predict celiac disease in children were calculated. The data from 240 children were calculated. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of tissue transglutaminase titers at ≥10× upper limit of normal were 75.4, 48.8, 87.7, 29.0, and 70.8 %, respectively. Similar data were noted in the other tissue transglutaminase titers (≥3× upper limit of normal, >100 U/ml, or >100 U/ml and >10× upper limit of normal). The positive predictive value of tissue transglutaminase titers at ≥3× upper limit of normal or higher was too low to predict celiac disease in children. Our data suggested that in routine clinical practice, high titers of tissue transglutaminase are not sufficient to diagnose celiac disease in North American children without intestinal biopsies.

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats.

PubMed

Gandini, Marco; Cerri, Simona; Pregel, Paola; Giusto, Gessica; Vercelli, Cristina; Iussich, Selina; Tursi, Massimiliano; Farca, Anna Maria

2016-05-01

To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury. Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

TUMOR SUPPRESSER GENE P53 EXPRESSION IN PREMALIGNANT LESIONS AND GASTRIC CARCINOMA - PROGNOSTIC VALUE

PubMed Central

Vukobrat-Bijedić, Zora; Radović, Svjetlana; Husić-Selimović, Azra; Gornjaković, Srđan

2007-01-01

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepa-tology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion. PMID:17489760

Endoscopically visualized lesions, histologic findings, and bacterial invasion in the gastrointestinal mucosa of dogs with acute hemorrhagic diarrhea syndrome.

PubMed

Unterer, S; Busch, K; Leipig, M; Hermanns, W; Wolf, G; Straubinger, R K; Mueller, R S; Hartmann, K

2014-01-01

Etiology of hemorrhagic gastroenteritis (HGE) syndrome in dogs is unknown and histopathologic and microbial investigations have only been performed post mortem. To identify characteristic intra vitam endoscopic and histologic mucosal lesions, as well as bacterial species, within the mucosa of dogs with HGE. Ten dogs diagnosed with HGE were included. Eleven dogs with gastroduodenoscopy and different intestinal diseases were used as controls for microbial changes. Dogs pretreated with antibiotics or diagnosed with any disease known to cause bloody diarrhea were excluded from the study. In this prospective study, gastrointestinal biopsies were collected from 10 dogs with HGE. Endoscopic and histologic changes were assessed according to WSAVA guidelines. Biopsies from the stomach, duodenum, ileum, and colon were investigated by histology and by immunohistochemistry for the presence of Clostridium spp. and parvovirus. The first duodenal biopsy taken with a sterile forceps was submitted for bacterial culture. Acute mucosal lesions were only found in the intestines, not in the stomach. Clostridium spp., identified as Clostridium perfringens in 6/9 cases, were detected on the small intestinal mucosa in all dogs with HGE, either by culture or immunohistopathology. In the control group, C. perfringens could only be cultured in one of 11 dogs. The results of this study demonstrate an apparent association between C. perfringens and the occurrence of acute hemorrhagic diarrhea. The term "HGE," which implies the involvement of the stomach, should be renamed as "acute hemorrhagic diarrhea syndrome." Copyright © 2013 by the American College of Veterinary Internal Medicine.

Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report.

PubMed

Niriella, Madunil A; Kodisinghe, S Kuleesha; De Silva, Arjuna P; Hewavisenthi, Janaki; de Silva, Hithanadura J

2016-08-24

Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.

Study on the effects of microencapsulated Lactobacillus delbrueckii on the mouse intestinal flora.

PubMed

Sun, Qingshen; Shi, Yue; Wang, Fuying; Han, Dequan; Lei, Hong; Zhao, Yao; Sun, Quan

2015-01-01

To evaluate the protective effects of microencapsulation on Lactobacillus delbrueckii by random, parallel experimental design. Lincomycin hydrochloride-induced intestinal malfunction mouse model was successfully established; then the L. delbrueckii microcapsule was given to the mouse. The clinical behaviour, number of intestinal flora, mucous IgA content in small intestine, IgG and IL-2 level in peripheral blood were monitored. The histological sections were also prepared. The L. delbrueckii microcapsule could have more probiotic effects as indicated by higher bifidobacterium number in cecal contents. The sIgA content in microcapsule treated group was significantly higher than that in non-encapsulated L. delbrueckii treated group (p < 0.05). Intestine pathological damage of the L. delbrueckii microcapsule-treated group showed obvious restoration. The L. delbrueckii microcapsules could relieve the intestinal tissue pathological damage and play an important role in curing antibiotic-induced intestinal flora dysfunction.

Use of a novel monoclonal antibody in diagnosis of Barrett's esophagus.

PubMed

Griffel, L H; Amenta, P S; Das, K M

2000-01-01

A novel monoclonal antibody (MAbDAS-1), that specifically reacts with colonic but not small intestinal epithelium, recognizes specialized columnar epithelium (SCE) in the esophagus. The frequency of its reactivity in biopsy specimens of patients with endoscopically suspected Barrett's Esophagus (BE) is examined. Fifty-two biopsy specimens of the distal esophagus from 38 patients were tested by immunoperoxidase method using MAbDAS-1. Fifty-four samples of cardia-type mucosa biopsied from the stomach were used as controls. Results were compared with histology and Alcian blue/high iron diamine (AB/HID). Of the 52 specimens, 29 had glandular epithelium and the rest had only squamous epithelium. Ten were diagnosed to have SCE by histology. All 10 samples reacted with MAbDAS-1 and with Alcian blue. Of the remaining 19 specimens, five also reacted with MAbDAS-1. None of the squamous epithelium and cardia specimens reacted with MAbDAS-1. MAbDAS-1 may detect intestinal metaplasia of the esophagus of colonic phenotype in the absence of histological evidence of SCE.

Monovalent Virus-Like Particle Vaccine Protects Guinea Pigs and Nonhuman Primates Against Infection with Multiple Marburg Viruses

DTIC Science & Technology

2008-05-01

illness and death. Guinea pig necropsy, histology & immunohistochemistry Two animals randomly selected from each group were eutha- nized on 6–7 days... Gastritis , neutrophilic - - - - - - +/++ +/++ - Intestine Cellular lysis - - - - - - + + + Enteritis, neutrophilic...isolates in both guinea pigs and NHPs. Clinical, histological and immunohisto- logical findings, restricted to six animals in the three RIBI-vaccinated

Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin.

PubMed

Araújo, Raquel Silva; Silveira, Ana Letícia Malheiros; de Sales E Souza, Éricka Lorenna; Freire, Rachel Horta; de Souza, Cristina Maria; Reis, Diego Carlos; Costa, Bruno Rocha Cordeiro; Sugimoto, Michelle Amantéa; Silveira, Josianne Nicácio; Dos Santos Martins, Flaviano; Cassali, Geovanni Dantas; Leite, Jacqueline Isaura Alvarez; Sousa, Lirlândia Pires; Ferreira, Adaliene Versiani Matos; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2017-08-30

Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use. Copyright © 2017. Published by Elsevier B.V.

Histological damage and inflammatory response elicited by Monobothrium wageneri (Cestoda) in the intestine of Tinca tinca (Cyprinidae)

PubMed Central

2011-01-01

Background Among the European cyprinids, tench, Tinca tinca (L.), and the pathological effects their cestodes may effect, have received very little or no attention. Most literature relating to Monobothrium wageneri Nybelin, 1922, a common intestinal cestode of tench, for example, has focused on aspects of its morphology rather than on aspects of the host-parasite interaction. Results Immunopathological and ultrastructural studies were conducted on the intestines of 28 tench, collected from Lake Piediluco, of which 16 specimens harboured tight clusters of numerous M. wageneri attached to the intestinal wall. The infection was associated with the degeneration of the mucosal layer and the formation of raised inflammatory swelling surrounding the worms. At the site of infection, the number of granulocytes in the intestine of T. tinca was significantly higher than the number determined 1 cm away from the site of infection or the number found in uninfected fish. Using transmission electron microscopy, mast cells and neutrophils were frequently observed in close proximity to, and inside, the intestinal capillaries; often these cells were in contact with the cestode tegument. At the host-parasite interface, no secretion from the parasite's tegument was observed. Intense degranulation of the mast cells was seen within the submucosa and lamina muscularis, most noticeably at sites close to the tegument of the scolex. In some instances, rodlet cells were encountered in the submucosa. In histological sections, hyperplasia of the mucous cells, notably those giving an alcian blue positive reaction, were evident in the intestinal tissues close to the swelling surrounding the worms. Enhanced mucus secretion was recorded in the intestines of infected tench. Conclusions The pathological changes and the inflammatory cellular response induced by the caryophyllidean monozoic tapeworm M. wageneri within the intestinal tract of an Italian population of wild tench is reported for the first time. PMID:22152408

Feasibility and scalability of spring parameters in distraction enterogenesis in a murine model.

PubMed

Huynh, Nhan; Dubrovsky, Genia; Rouch, Joshua D; Scott, Andrew; Stelzner, Matthias; Shekherdimian, Shant; Dunn, James C Y

2017-07-01

Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model. A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology. Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm (P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm (P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine. Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia.

PubMed

Figueira, R L; Gonçalves, F L; Simões, A L; Bernardino, C A; Lopes, L S; Castro E Silva, O; Sbragia, L

2016-06-23

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

PubMed Central

Figueira, R.L.; Gonçalves, F.L.; Simões, A.L.; Bernardino, C.A.; Lopes, L.S.; Castro e Silva, O.; Sbragia, L.

2016-01-01

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID:27356106

Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

PubMed Central

2013-01-01

Background Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Methods Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. Results Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. Conclusion Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients. PMID:23672582

[Quality of diagnostic procedures and frequency of endoscopically defined diseases of the upper gastrointestinal tract].

PubMed

Bartels, F; Hahn, H-J; Stolte, M; Schmidt-Wilcke, H A

2003-04-01

The aim of this clinical investigation was to register the frequency of endoscopically defined diseases of the upper intestinal tract in a given region (Münster and Münsterland) within the period of one year (1.8.1999-31.7.2000). Furthermore, we tried to get an impression on the quality of the upper intestinoscopies by standardised conditions which had been developed by a steering committee (endoscopists and pathologists). 20 physicians (internal specialists and gastroenterologists) examined non-preselected patients and registered all relevant findings in the upper intestinal tract. The following items were of special interest: sex, age, operations in the past, indication, way of preparation, local findings (in the upper intestinal tract), and histological assessment. The examination forms were gathered, checked for completeness and evaluated statistically. Within the given period 8859 examinations forms (45.2% male and 54% female) could be evaluated. In 16% of the patients a reflux oesophagitis was diagnosed, three times more frequently than could have been expected anamnestically regarding the patients' complaints. In 274 patients (3%) the endoscopist suspected a Barrett's oesophagus; the according histological examination confirmed this suspicion in only 125 cases. Furthermore 17 adenocarcinomas and 13 squamous cell carcinomas were found. Macroscopically 44 polyps were registered but not all of them were biopsied. In 257 patients oesophageal varices (of varying degrees) were described. Only in 30.7% of the patients a H. pylori infection (diagnosed by urease test and by histological examination) was detected in the mucosa of the stomach. In 172 patients a gastritis was macroscopically suspected but the following histological assessments were not sufficient. The prevalence of gastric ulcers was 10 %, higher than the prevalence of duodenal ulcers. Only in 50% of the patients with a duodenal ulcer a H. pylori infection could be detected. In 51 cases carcinomas (diagnosis histologically confirmed) were found with the same ratio of the diffuse type and the intestinal type. In 18 patients a carcinoma could be detected in the neighbouring area of gastric ulcers. The endoscopic findings in this investigation do not differ significantly from the results found in literature. It is important that there are more gastric ulcers than duodenal ulcers. This can be explained by the frequent use of PPIs which are prescribed additionally to NSARs and ASS. The deficits of histological diagnostics on Barett's oesophagus and gastritis were remarkable. An improvement of the endoscopic and histologic assessment quality by valid standards systematically applied should be aimed at in future. Furthermore it could be helpful to use the same nomenclature for pathologic findings to intensify the co-operation between the physicians in hospitals and the practitioners.

Animal experimental studies using small intestine endoscope

PubMed Central

Liu, Jin-Hua; Liu, Dan-Yang; Wang, Li; Han, Li-Ping; Qi, Zhe-Yu; Ren, Hai-Jun; Feng, Yan; Luan, Feng-Ming; Mi, Liang-Tian; Shan, Shu-Mei

2017-01-01

AIM To assess the feasibility and safety of a novel enteroscope, negative-pressure suction endoscope in examining the small intestine of a porcine model. METHODS In vitro experiments in small intestinal loops from 20 pigs and in vivo experiments in 20 living pigs were conducted. RESULTS In in vitro experiments, a negative pressure of > 0.06 MPa was necessary for optimal visualization of the intestine, and this pressure did not cause gross or histological damage to the mucosa. For satisfactory examination of the small intestine in vivo, higher negative pressure (> 1.00 MPa) was required. Despite this higher pressure, the small intestine did not show any gross or microscopic damage in the suctioned areas. The average time of examination in the living animals was 60 ± 7.67 min. The animals did not experience any apparent ill effects from the procedure. CONCLUSION Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases. PMID:28611521

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

PubMed

Rentea, Rebecca M; Lam, Vy; Biesterveld, Ben; Fredrich, Katherine M; Callison, Jennifer; Fish, Brian L; Baker, John E; Komorowski, Richard; Gourlay, David M; Otterson, Mary F

2016-10-01

Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome. Copyright © 2016 Elsevier Inc. All rights reserved.

Erdosteine and ebselen as useful agents in intestinal ischemia/reperfusion injury.

PubMed

Tunc, Turan; Uysal, Bulent; Atabek, Cuneyt; Kesik, Vural; Caliskan, Bahadir; Oztas, Emin; Ersoz, Nail; Oter, Sukru; Guven, Ahmet

2009-08-01

Reactive oxygen and nitrogen species generated during reperfusion of the tissue are characteristic of ischemia/reperfusion (I/R) injury. The purpose of the present study was to investigate whether erdosteine and ebselen, molecules with antioxidant properties and peroxynitrite scavenging capability, respectively, can reduce oxidative stress and histological damage in the rat small bowel subjected to mesenteric I/R injury. Forty Sprague-Dawley rats were divided into five groups equally: sham, I/R, I/R plus erdosteine, I/R plus ebselen, and I/R plus erdosteine and ebselen. Intestinal ischemia for 45 min and reperfusion for 3 d were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehide (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitrite/nitrate (NO(x)) level and histological changes. Intestinal I/R resulted in increased tissue MDA, PCC, and NO(x) levels and decreased SOD and GPx activities. Both erdosteine and ebselen alone significantly decreased MDA, PCC, and NO(x) levels and increased antioxidant enzymes activities, but all values were different from control. These changes almost returned to control values in the group treated with erdostein and ebselen. Histopathologically, the intestinal injury in rats treated with erdosteine and ebselen as well as combination were less than I/R group. Both erdosteine and ebselen were able to attenuate I/R injury of the intestine via inhibition of lipid peroxidation and protein oxidation, maintenance of antioxidant, and free radical scavenger properties. Nevertheless, combination treatment showed more promising results, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing intestinal I/R injury.

Epstein-Barr virus in inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders.

PubMed

Nissen, Loes H C; Nagtegaal, Iris D; de Jong, Dirk J; Kievit, Wietske; Derikx, Lauranne A A P; Groenen, Patricia J T A; van Krieken, J Han J M; Hoentjen, Frank

2015-05-01

Inflammatory bowel disease (IBD) patients on thiopurine therapy are at increased risk of Epstein-Barr virus (EBV)-associated lymphomas. This virus is frequently detected in the intestinal mucosa of IBD patients and may cause a wide spectrum of lymphoproliferations similar to post-transplantation lymphoproliferative disorders (PTLDs). We aimed to assess whether histological aberrations aid in predicting EBV presence and to correlate histological assessment and EBV load with disease outcome in IBD. We included all IBD patients from our centre who underwent EBV testing of intestinal biopsies between January 2004 and October 2013. All biopsies were classified according to the WHO PTLD classification and the EBV load was scored per high-power field (HPF). Clinical data were collected from patient charts. Reported clinical outcomes included colectomy, need for chemotherapy and mortality. Our cohort included 58 patients: 28 were EBV-positive and 30 EBV-negative. An atypical infiltrate was seen more frequently in EBV-positive than in EBV-negative patients (57.1 versus 3.3%; p < 0.001). A high EBV load occurred more frequently in EBV-positive patients undergoing colectomy than in EBV-positive patients without colectomy (50.0 versus 10.0%; p = 0.048). Monomorphic lymphoproliferative disorders, including two overt lymphomas, were present in 10 patients. Reduction of immunosuppression resulted in histological normalization and loss of EBV expression in seven of eight non-lymphoma patients. The presence of atypical infiltrate in the intestinal mucosa of IBD patients warrants EBV testing. Reduction of immunosuppression is an effective strategy to achieve morphological normalization and loss of EBV. Lymphoproliferation related to IBD appears to have less aggressive clinical behaviour than PTLDs. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

PubMed Central

Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q.; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R.; Pothoulakis, Charalabos

2015-01-01

In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis. PMID:25591865

Lactobacillus plantarum culture supernatants improve intestinal tissue exposed to deoxynivalenol.

PubMed

Maidana, L G; Gerez, J; Pinho, F; Garcia, S; Bracarense, A P F L

2017-10-02

In the present study, histological, morphometrical and ultrastructural analysis were performed to investigate intestinal mucosa changes in piglets exposed to deoxynivalenol alone or associated with two strains of Lactobacillus plantarum and the respective culture supernatants. Jejunal explants were incubated for 4h in culture medium with a) only culture medium (DMEM, control group), b) deoxynivalenol (DON, 10μM), c) heat-inactivated Lactobacillus plantarum strain1 - LP1 (1.1×10 8 CFU/ml) plus DON, d) heat-inactivated Lactobacillus plantarum strain2-LP2 (2.0×10 9 CFU/ml) plus DON, e) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON, and f) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1) plus DON. Explants exposed to DON and DON plus LP1 and LP2 showed a significant increase in histological changes (mainly villi atrophy and apical necrosis) and a significant decrease in villi height when compared to unexposed explants. However, explants treated with CS1+DON and CS2+DON remained similar to the control group both in histological and morphometrical aspects. DON also induced a significant decrease in goblet cell density compared to control whereas CS1+DON treatment induced an increase in the number of goblet cells in comparison to DON explants. In addition, ultrastructural assessment showed control, CS1+DON and CS2+DON explants with well delineated finger shape villi, meanwhile DON-treated, LP1+DON and LP2+DON explants showed a severe villi atrophy with leukocytes exudation on the intestinal surface. Taken together, our results indicate that the culture supernatant treatment reduced the toxic effects induced by DON on intestinal tissue and may contribute as an alternative strategy to reduce mycotoxin toxicity. Copyright © 2017 Elsevier GmbH. All rights reserved.

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

NASA Astrophysics Data System (ADS)

Bista, Rajan K.; Uttam, Shikhar; Hartman, Douglas J.; Qiu, Wei; Yu, Jian; Zhang, Lin; Brand, Randall E.; Liu, Yang

2012-06-01

The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and evaluation of chemopreventive treatment.

Controlling Salmonella infection in weanling pigs through water delivery of direct-fed microbials or organic acids: Part II. Effects on intestinal histology and active nutrient transport

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the effects of water-delivered direct-fed microbials (DFM) or organic acids on intestinal morphology and active nutrient absorption in weanling pigs following deliberate Salmonella infection. Pigs (n = 88) were weaned at 19 ± 2 d of age and assigned to one...

An examination of the intestinal tract of Atlantic salmon, Salmo salar L., parr fed different varieties of soy and maize.

PubMed

Sanden, M; Berntssen, M H G; Krogdahl, A; Hemre, G-I; Bakke-McKellep, A-M

2005-06-01

This study was conducted to investigate the long-term effects of feeding plant products from both traditional breeding and from biotechnology on intestinal somatic indices, histology and cell proliferation in first-feeding Atlantic salmon, Salmo salar L. (initial weight 0.21 +/- 0.02 g). A standard fishmeal diet (standard fishmeal) was formulated to contain fishmeal as the sole protein source and suprex maize as the main starch source. Six experimental diets were then developed: two in which some of the fishmeal was replaced with commercially available, genetically modified Roundup Ready full-fat soybean meal (GM-soy) or commercially available, non-GM full-fat soybean meal (nGM-soy) at a level of 12.5% of the total diet, and four diets in which the suprex maize was replaced with two lines of GM-maize (Dekalb 1; D1 and Pioneer 1; P1), both products of event MON810, and their half-sibling non-GM counterparts (Dekalb 2; D2 and Pioneer 2; P2), at a level of 12.1% of total diet. Each diet was fed to fish in triplicate tanks and the experiment lasted for 8 months, during which the fish reached a final weight of 101-116 g. There was no significant effect of diet on the intestinal indices, nor were histological changes observed in the pyloric caeca or mid intestine. In the distal intestine, one of nine sampled fish fed nGM-soy showed moderate changes, two of nine sampled fish fed GM-soy showed changes, one with moderate and one with severe changes, and two of nine fish fed nGM-maize D2 had moderate changes. Using a monoclonal antibody against proliferating cell nuclear antigen (PCNA), cell proliferative responses to the experimental diets were assessed. In fish fed both soy diets, a significantly higher (P < 0.05) cell proliferation response was observed in the distal intestine concomitant with an increased localization of PCNA positive cells along the whole distal intestinal folds. The PCNA response among the nGM-soy group was significantly higher compared with all the other diet groups. In contrast, for fish exposed to dietary maize (type D) compared with fish fed the standard fishmeal, the soy-diets (GM-soy and nGM-soy) and maize (type P), a significantly lower (P < 0.05) cell proliferation response was observed in the distal intestine. Results indicated that the GM plant products investigated in this study, at about 12% inclusion level, were as safe as commercially available non-GM products, at least in terms of their effect on indices and histological parameters of the Atlantic salmon intestinal tract.

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray.

PubMed

Jinawath, Natini; Furukawa, Yoichi; Hasegawa, Suguru; Li, Meihua; Tsunoda, Tatsuhiko; Satoh, Seiji; Yamaguchi, Toshiharu; Imamura, Hiroshi; Inoue, Masatomo; Shiozaki, Hitoshi; Nakamura, Yusuke

2004-09-02

Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

Characterization of naturally developing small intestinal bacterial overgrowth in 16 German shepherd dogs.

PubMed

Willard, M D; Simpson, R B; Fossum, T W; Cohen, N D; Delles, E K; Kolp, D L; Carey, D P; Reinhart, G A

1994-04-15

Sixteen German Shepherd Dogs were found, via quantitative microbial culture of intestinal fluid samples, to have small intestinal bacterial overgrowth (IBO) over an 11-month period. All dogs were deficient in serum IgA. Consistent clinical signs suggestive of an alimentary tract disorder were not observed. Serum cobalamin determinations were not helpful in detecting IBO. Serum folate concentrations had variable sensitivity and specificity for detecting dogs from which we could culture > or = 1 x 10(5) bacterial/ml from intestinal fluid samples in the nonfed state. Histologic and intestinal mucosal cytologic examinations were not useful in detecting IBO. Substantial within-dog and between-dog variation was found in the numbers and species of bacteria in the intestines. The difficulty in diagnosing IBO, the variability in organisms found in individual dogs on repeated sampling, the likelihood that intestinal fluid microbial cultures failed to diagnose IBO in some dogs, and the potential of IBO to be clinically inapparent were the most important findings in this study.

Histologic definition of gastro-esophageal reflux disease.

PubMed

Chandrasoma, Parakrama T

2013-07-01

To review recent data supporting the development of new histology-based definitions of gastro-esophageal reflux disease (GERD). Three precisely definable columnar epithelial types--cardiac, oxyntocardiac and intestinal--may be interposed between esophageal squamous epithelium and gastric oxyntic (acid secreting) mucosa. This enables definition of a new histologic concept: the squamo-oxyntic gap. The squamo-oxyntic gap is zero or very small in autopsies performed on patients without evidence of GERD. The gap progressively increases in length with the severity of GERD, indicating that the squamo-oxyntic gap is a marker for chronic GERD. The distal part of the gap lines gastric-type rugal folds and, therefore, is distal to the present endoscopic definition of the gastro-esophageal junction. I contend that this distal gap segment (which has esophageal submucosal glands) is actually the dilated distal esophagus; this is the pathologic correlate of destruction of the abdominal segment of the lower esophageal sphincter. The dilated distal esophagus is mistaken for 'gastric cardia' by present endoscopic definitions. I believe that these data support the adoption of novel histologic definitions of GERD as follows: the presence of any squamo-oxyntic gap defines GERD; the length of the gap is a measure of severity of chronic GERD; and the presence of intestinal metaplasia in the gap defines Barrett esophagus and cancer risk.

[Pneumatosis cystoides intestinalis complicated with intestinal volvulus].

PubMed

Fuenmayor, Carmen Elena; Gainza, Carlos; García, Maryori; Zambrano, Richard; Torres, Gledys; Hernández, Yohanys; García, Anna

2017-01-01

Pneumatosis cystoides intestinalis is a rare condition in which multiple gas-filled cysts are found within the wall of the gastrointestinal tract either in the subserosa or submucosa. Its pathogenesis is uncertain and several pathogenic mechanisms have been proposed to explain its origin. The case of a male patient of 46 years with previous diagnosis of pneumatosis cystic intestinalis, who consulted for abdominal pain, vomiting and fever (39 °C) is presented. By the time of admission ther were signs of peritoneal irritation. The X-ray abdominal reported distension and intestinal hydro-air levels. Exploratory laparotomy was performed and revealed small bowel volvulus with strangulation of some intestinal segment. Histological diagnosis was pneumatosis cystic intestinalis complicated with Infarction trans-mural by intestinal volvulus. The patient evolved satisfactorily.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

PubMed

Eto, K; Ohyama, S; Yamaguchi, T; Wada, T; Suzuki, Y; Mitsumori, N; Kashiwagi, H; Anazawa, S; Yanaga, K; Urashima, M

2006-09-01

To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

Small intestinal volvulus in a free-ranging female dugong (Dugong dugon).

PubMed

Gillespie, A; Burgess, E; Lanyon, J; Owen, H

2011-07-01

An adult female dugong (Dugong dugon) was found dead and floating in Moreton Bay, Queensland, Australia. This animal was found to have a 360° mesenteric volvulus with infarction of the associated segment of small intestine, and fibrinous peritonitis. Mortality was attributed to the volvulus and its sequelae. The cause was not apparent on gross or histological examination. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Carbohydrate catabolic flexibility in the mammalian intestinal commensal Lactobacillus ruminis revealed by fermentation studies aligned to genome annotations

PubMed Central

2011-01-01

Background Lactobacillus ruminis is a poorly characterized member of the Lactobacillus salivarius clade that is part of the intestinal microbiota of pigs, humans and other mammals. Its variable abundance in human and animals may be linked to historical changes over time and geographical differences in dietary intake of complex carbohydrates. Results In this study, we investigated the ability of nine L. ruminis strains of human and bovine origin to utilize fifty carbohydrates including simple sugars, oligosaccharides, and prebiotic polysaccharides. The growth patterns were compared with metabolic pathways predicted by annotation of a high quality draft genome sequence of ATCC 25644 (human isolate) and the complete genome of ATCC 27782 (bovine isolate). All of the strains tested utilized prebiotics including fructooligosaccharides (FOS), soybean-oligosaccharides (SOS) and 1,3:1,4-β-D-gluco-oligosaccharides to varying degrees. Six strains isolated from humans utilized FOS-enriched inulin, as well as FOS. In contrast, three strains isolated from cows grew poorly in FOS-supplemented medium. In general, carbohydrate utilisation patterns were strain-dependent and also varied depending on the degree of polymerisation or complexity of structure. Six putative operons were identified in the genome of the human isolate ATCC 25644 for the transport and utilisation of the prebiotics FOS, galacto-oligosaccharides (GOS), SOS, and 1,3:1,4-β-D-Gluco-oligosaccharides. One of these comprised a novel FOS utilisation operon with predicted capacity to degrade chicory-derived FOS. However, only three of these operons were identified in the ATCC 27782 genome that might account for the utilisation of only SOS and 1,3:1,4-β-D-Gluco-oligosaccharides. Conclusions This study has provided definitive genome-based evidence to support the fermentation patterns of nine strains of Lactobacillus ruminis, and has linked it to gene distribution patterns in strains from different sources. Furthermore, the study has identified prebiotic carbohydrates with the potential to promote L. ruminis growth in vivo. PMID:21995520

Beneficial effects of dexpanthenol on mesenteric ischemia and reperfusion injury in experimental rat model.

PubMed

Cagin, Yasir Furkan; Atayan, Yahya; Sahin, Nurhan; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Tagluk, Mehmet Emin; Tanbek, Kevser; Yildiz, Azibe

2016-01-01

It has been reported that intestinal ischemia-reperfusion (I/R) injury results from oxidative stress caused by increased reactive oxygen species. Dexpanthenol (Dxp) is an alcohol analogue with epitelization, anti-inflammatory, antioxidant, and increasing peristalsis activities. In the present study, the aim was to investigate protective and therapeutic effects of Dxp against intestinal I/R injury. Overall, 40 rats were assigned into five groups including one control, one alone Dxp, and three I/R groups (40-min ischemia; followed by 2-h reperfusion). In two I/R groups, Dxp (500 mg/kg, i.m.) was given before or during ischemia. The histopathological findings including apoptotic changes, and also tissue and serum biochemical parameters levels, were determined. Oxidative stress and ileum damage were assessed by biochemical and histological examination. In the control (n = 8) and alone Dxp (n = 8; 500 mg/kg, i.m. of Dxp was given at least 30 min before recording), groups were incised via laparotomy, and electrical activity was recorded from their intestines. In this experiment, the effect of Dxp on the motility of the intestine was examined by analyzing electrical activity. In ileum, oxidant levels were found to be higher, while antioxidant levels were found to be lower in I/R groups when compared with controls. Dxp approximated high levels of oxidants than those in the control group, while it increased antioxidant values compared with I/R groups. Histopathological changes caused by intestinal I/R injury and histological improvements were observed in both groups given Dxp. In the Dxp group, electrical signal activity markedly increased compared with the control group. Here, it was seen that Dxp had protective and therapeutic effects on intestinal I/R injury and gastrointestinal system peristaltism.

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

PubMed

Yang, R; Liu, Q; Wu, E X; Pescovitz, M D; Collins, M H; Kopecky, K K; Grosfeld, J L

1994-02-01

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Morphological changes of the intestine in experimental acute intestinal infection in the treatment of colloidal silver].

PubMed

Polov'ian, E S; Chemich, N D; Moskalenko, R A; Romaniuk, A N

2012-06-01

At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.

Are histological alterations observed in the gallbladder precancerous lesions?

PubMed Central

Meirelles-Costa, Adriana Lúcia Agnelli; Bresciani, Claudio José Caldas; Perez, Rodrigo Oliva; Bresciani, Barbara Helou; Siqueira, Sheila Aparecida C.; Cecconello, Ivan

2010-01-01

INTRODUCTION Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required. PMID:20186297

Fecal calprotectin concentrations in adult dogs with chronic diarrhea.

PubMed

Grellet, Aurélien; Heilmann, Romy M; Lecoindre, Patrick; Feugier, Alexandre; Day, Michael J; Peeters, Dominique; Freiche, Valérie; Hernandez, Juan; Grandjean, Dominique; Suchodolski, Jan S; Steiner, Jorg M

2013-05-01

To evaluate fecal calprotectin concentrations in healthy dogs and dogs with chronic diarrhea, to identify cutoff values for fecal calprotectin concentrations for use in differentiating dogs with chronic diarrhea and a canine chronic enteropathy clinical activity index (CCECAI) < 12 from dogs with chronic diarrhea and a CCECAI ≥ 12, and to evaluate the association between histologic evidence of intestinal mucosal changes and fecal calprotectin concentrations in dogs with chronic diarrhea. Fecal samples from 96 adult dogs (27 dogs with chronic diarrhea and 69 healthy control dogs). Severity of clinical signs was evaluated on the basis of the CCECAI scoring system. Endoscopy was performed in all dogs with chronic diarrhea, and mucosal biopsy specimens were evaluated histologically. Fecal calprotectin concentration was quantified via radioimmunoassay. Fecal calprotectin concentrations were significantly higher in dogs with chronic diarrhea than in healthy control dogs. Fecal calprotectin concentrations were also significantly higher in dogs with a CCECAI ≥ 12, compared with concentrations for dogs with a CCECAI between 4 and 11. Fecal calprotectin concentrations were significantly higher in dogs with chronic diarrhea associated with histologic lesions, compared with concentrations in control dogs, and were significantly correlated with the severity of histologic intestinal lesions. Among dogs with chronic diarrhea, the best cutoff fecal calprotectin concentration for predicting a CCECAI ≥ 12 was 48.9 μg/g (sensitivity, 53.3%; specificity, 91.7%). Fecal calprotectin may be a useful biomarker in dogs with chronic diarrhea, especially dogs with histologic lesions.

Oral administration of liquid iron preparation containing excess iron induces intestine and liver injury, impairs intestinal barrier function and alters the gut microbiota in rats.

PubMed

Fang, Shenglin; Zhuo, Zhao; Yu, Xiaonan; Wang, Haichao; Feng, Jie

2018-05-01

The aim of this study was to determine the toxicological effects of excess iron in a liquid iron preparation (especially on intestinal barrier function) and the possible etiology of side effects or diseases caused by the excess iron. In study 1, forty male Sprague-Dawley rats (4-5 wk old) were subjected to oral gavage with 1 ml vehicle (0.01 mol/L HCl) or 1 ml liquid iron preparation containing 8 mg, 16 mg or 24 mg of iron for 30 d. Iron status, oxidative stress, histology (H&E staining), ultrastructure (electron microscopy) and apoptosis (TUNEL assay) in the intestines and liver were assessed. The cecal microbiota was evaluated by 16S rRNA sequencing. In study 2, twenty rats with the same profile as above were subjected to oral gavage with 1 ml vehicle or 24 mg Fe for 30 d. The intestinal barrier function was determined by in vivo studies and an Ussing chamber assay; tight junction proteins and serum pro-inflammatory cytokines were observed by enzyme-linked immunosorbent assay. In study 1, the intestinal mucosa and liver showed apparent oxidative stress. In addition, iron concentration-dependent ultrastructural alterations to duodenal enterocytes and hepatocytes and histological damage to the colonic mucosa were detected. Notably, apoptosis was increased in duodenal enterocytes and hepatocytes. Impaired intestinal barrier function and lower expression of intestinal tight junction proteins were observed, and the phenotype was more severe in the colon than in the duodenum. A trend toward higher expression of serum pro-inflammatory cytokines might indicate systemic inflammation. Furthermore, the caecal microbiota showed a significant change, with increased Defluviitaleaceae, Ruminococcaceae, and Coprococcus and reduced Lachnospiraceae and Allobaculum, which could mediate the detrimental effects of excess iron on gut health. We concluded that excessive iron exposure from liquid iron preparation induces oxidative stress and histopathological alterations in the intestine and liver. Impaired intestinal barrier function could increase iron transportation, and inflammation along with oxidative stress-enhanced liver iron deposition may cause further liver injury in a vicious circle. These effects were accompanied by lower intestinal segment damage and altered gut microbial composition of rats toward a profile with an increased risk of gut disease. Copyright © 2018 Elsevier GmbH. All rights reserved.

Survival after total body irradiation: Effects of irradiation of exteriorized small intestine. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vriesendorp, H.M.; Vigneulle, R.M.; Kitto, G.

1993-12-31

Rats receiving lethal irradiation to their exteriorized small intestine with pulsed 18 MVp bremsstrahlung radiation live about 4 days longer than rats receiving a dose of total-body irradiation (TBI) causing intestinal death. The LD50 for intestinal irradiation is approximately 6 Gy higher than the LD50 for intestinal death after TBI. Survival time after exteriorized intestinal irradiation can be decreased, by adding abdominal irradiation. Adding thoracic or pelvic irradiation does not alter survival time. Shielding of large intestine improves survival after irradiation of the rest of the abdomen while the small intestine is also shielded. The kinetics of histological changes inmore » small intestinal tissues implicate the release of humoral factors after irradiation of the abdomen. Radiation injury develops faster in the first (proximal) 40 cm of the small intestine and is expressed predominantly as shortening in villus height. In the last (distal) 40 cm of the small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Irradiation (20 Gy) of the proximal small intestine causes 92 % mortality (median survival 10 days). Irradiation (20 Gy) of the distal small intestine causes 27% mortality (median survival > 30 days). In addition to depletion of crypt stem cells in the small intestine, other issues (humoral factors, irradiated subsection of the small intestine and shielding of the large intestine) appear to influence radiation-induced intestinal mortality.« less

Evaluation of architectural and histopathological biomarkers in the intestine of brown trout (Salmo trutta Linnaeus, 1758) challenged with environmental pollution.

PubMed

Barišić, Josip; Filipović Marijić, Vlatka; Mijošek, Tatjana; Čož-Rakovac, Rozelindra; Dragun, Zrinka; Krasnići, Nesrete; Ivanković, Dušica; Kružlicová, Dáša; Erk, Marijana

2018-06-14

In the present study novel histopathological approach, using fish intestine as a sensitive bioindicator organ of pollution impact in the freshwater ecosystem, was proposed. Histopathological alterations were compared between native brown trout (Salmo trutta Linnaeus, 1758) from the reference (Krka River spring) and pollution impacted location (influence of technological/municipal wastewaters and agricultural runoff near the Town of Knin) of the karst Krka River in Croatia. In brown trout from both locations, severe parasitic infestation with acanthocephalan species Dentitruncus trutae was found, enabling evaluation of acanthocephalan infestation histopathology, which indicated parasite tissue reaction in a form of inflammatory, necrotic and hyperplastic response that extended throughout lamina epithelialis mucosae, lamina propria, and lamina muscularis mucosae. New semi-quantitative histological approach was proposed in order to foresee alterations classified in three reaction patterns: control tissue appearance, moderate (progressive) tissue impairment and severe (regressive and inflammatory) tissue damage. The most frequent progressive alteration was hyperplasia of epithelium on the reference site, whereas the most frequent regressive alterations were atrophy and necrosis seen on the polluted site. Furthermore, histopathological approach was combined with micromorphological and macromorphological assessment as an additional indicator of pollution impact. Among 15 observed intestinal measures, two biomarkers of intestinal tissue damage were indicated as significant, height of supranuclear space (hSN) and number of mucous cells over 100 μm fold distance of intestinal mucosa (nM), which measures were significantly lower in fish from polluted area compared to the reference site. Obtained results indicated that combined histological and morphological approach on fish intestinal tissue might be used as a valuable biological tool for assessing pollution impact on aquatic organisms. Therefore, semi quantitative scoring and multiparametric morphological assessment of intestinal tissue lesion magnitude should become a common approach to handle environmental pollution impact. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation.

PubMed

Ferencz, Andrea; Racz, Boglarka; Tamas, Andrea; Reglodi, Dora; Lubics, Andrea; Nemeth, Jozsef; Nedvig, Klara; Kalmar-Nagy, Karoly; Horvath, Ors Peter; Weber, Gyorgy; Roth, Erzsebet

2009-02-01

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.

Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels.

PubMed

Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B; Parikh, Alexander; Revetta, Frank; Washington, M Kay; Vnencak-Jones, Cindy; Shi, Chanjuan

2014-05-01

Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (P<0.01). Expression of amphiregulin correlated with better differentiation (P<0.01), but no difference was observed between two major histologic types. Expression and activation of EGFR was more commonly seen in the pancreatobiliary type (P<0.01). Mutations were detected in 50% of the pancreatobiliary type and 60% of the intestinal type. KRAS was the most common gene mutated in the pancreatobiliary type (42%) as well as the intestinal type (52%). Other mutations detected included PIK3CA, SMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

PubMed Central

Koon, Hon Wai; Ho, Samantha; Hing, Tressia C.; Cheng, Michelle; Chen, Xinhua; Ichikawa, Yoshi; Kelly, Ciarán P.

2014-01-01

Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins. PMID:24890583

Mesenteric lipoblastoma presenting as a small intestinal volvulus in an infant: A case report and literature review.

PubMed

Nagano, Yuka; Uchida, Keiichi; Inoue, Mikihiro; Ide, Shozo; Shimura, Tadanobu; Hashimoto, Kiyoshi; Koike, Yuki; Kusunoki, Masato

2017-01-01

A 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus. Copyright © 2013. Published by Elsevier Taiwan.

Diagnostic and Research Aspects of Small Intestinal Disaccharidases in Coeliac Disease

PubMed Central

Ciclitira, Paul J.

2017-01-01

Disaccharidases (DS) are brush border enzymes embedded in the microvillous membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a general decrease of DS activities is seen. This manuscript reviews different aspects of DS activities in CD: their utility in the diagnosis and their application to in vitro toxicity testing. The latter has never been established in CD research. However, with the recent advances in small intestinal organoid techniques, DS might be employed as a biomarker for in vitro studies. This includes establishment of self-renewing epithelial cells raised from tissue, which express differentiation markers, including the brush border enzymes. Determining duodenal DS activities may provide additional information during the diagnostic workup of CD: (i) quantify the severity of the observed histological lesions, (ii) provide predictive values for the grade of mucosal villous atrophy, and (iii) aid diagnosing CD where minor histological changes are seen. DS can also provide additional information to assess the response to a gluten-free diet as marked increase of their activities occurs four weeks after commencing it. Various endogenous and exogenous factors affecting DS might also be relevant when considering investigating the role of DS in other conditions including noncoeliac gluten sensitivity and DS deficiencies. PMID:28512643

[Celiac disease in a group of children and adolescents with type 1 diabetes mellitus].

PubMed

Brandt, Katia G; Silva, Giselia A P; Antunes, Margarida M C

2004-12-01

To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.

[Surgical therapy of segmental jejunal, primary intestinal lymphangiectasia].

PubMed

Kneist, W; Drescher, D G; Hansen, T; Kreitner, K F; Lang, H

2013-06-01

Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction. Diagnosis depends on clinical examination and histological findings. Conservative treatment modalities include a low-fat diet and enteral nutritional therapy in order to reduce enteric protein loss and to improve fat metabolism. Other treatment options consist of administration of antiplasmin or octreotide to lower lymph flow and secretion. We report on a 58-year-old patient who underwent exploratory laparotomy due to a worsening physical status, recurrent chylaskos and leg oedema under conservative dietary therapy. Intraoperative findings showed a typical PIL of the jejunum about 20 cm distal to the Treitz's ligament. Histological examinations confirmed this diagnosis. One year after segmental small bowel resection (105 cm) with end-to-end anastomosis the patient is healthy, free of symptoms, has gained weight and his serum protein level has increased. Intraabdominal ascites and leg oedema have not reoccurred since.

Effects of Clostridium perfringens iota toxin in the small intestine of mice.

PubMed

Redondo, Leandro M; Redondo, Enzo A; Dailoff, Gabriela C; Leiva, Carlos L; Díaz-Carrasco, Juan M; Bruzzone, Octavio A; Cangelosi, Adriana; Geoghegan, Patricia; Fernandez-Miyakawa, Mariano E

2017-12-01

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases. Published by Elsevier Ltd.

Effects of dietary Tenebrio molitor meal inclusion in free-range chickens.

PubMed

Biasato, I; De Marco, M; Rotolo, L; Renna, M; Lussiana, C; Dabbou, S; Capucchio, M T; Biasibetti, E; Costa, P; Gai, F; Pozzo, L; Dezzutto, D; Bergagna, S; Martínez, S; Tarantola, M; Gasco, L; Schiavone, A

2016-12-01

Insects are currently being considered as a novel protein source for animal feeds, because they contain a large amount of protein. The larvae of Tenebrio molitor (TM) have been shown to be an acceptable protein source for broiler chickens in terms of growth performance, but till now, no data on histological or intestinal morphometric features have been reported. This study has had the aim of evaluating the effects of dietary TM inclusion on the performance, welfare, intestinal morphology and histological features of free-range chickens. A total of 140 medium-growing hybrid female chickens were free-range reared and randomly allotted to two dietary treatments: (i) a control group and (ii) a TM group, in which TM meal was included at 75 g/kg. Each group consisted of five pens as replicates, with 14 chicks per pen. Growth performance, haematological and serum parameters and welfare indicators were evaluated, and the animals were slaughtered at the age of 97 days. Two birds per pen (10 birds/treatment) were submitted to histological (liver, spleen, thymus, bursa of Fabricius, kidney, heart, glandular stomach and gut) and morphometric (duodenum, jejunum and ileum) investigations. The inclusion of TM did not affect the growth performance, haematological or serum parameters. The morphometric and histological features were not significantly affected either, thus suggesting no influence on nutrient metabolization, performance or animal health. Glandular stomach alterations (chronic flogosis with epithelial squamous metaplasia) were considered paraphysiological in relation to free-range farming. The observed chronic intestinal flogosis, with concomitant activation of the lymphoid tissue, was probably due to previous parasitic infections, which are very frequently detected in free-range chickens. In conclusion, the findings of this study show that yellow mealworm inclusion does not affect the welfare, productive performances or morphological features of free-range chickens, thus confirming that TM can be used safely in poultry diets. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

PubMed

Yuki, T; Amano, Y; Kushiyama, Y; Takahashi, Y; Ose, T; Moriyama, I; Fukuhara, H; Ishimura, N; Koshino, K; Furuta, K; Ishihara, S; Adachi, K; Kinoshita, Y

2006-05-01

Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

PubMed Central

Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Kirman, Christopher R.; Harris, Mark A.

2013-01-01

Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors. PMID:23445218

Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice.

PubMed

Marsh, Lorraine; Coletta, P Louise; Hull, Mark A; Selby, Peter J; Carding, Simon R

2012-01-01

ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length of the small intestine and colon. Currently little is known about the role of the immune system in regulating intestinal tumorigenesis in these animals. This study characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect that T cells expressing either γδ or αβ encoded T cell receptors (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme-mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared with wild-type IELs. Analysis of ApcMin/+ mice crossed with αβ T-cell deficient (TcRβ-/-) or γδ T-cell deficient (TcRδ-/-) mice on the same genetic background revealed decreased tumour multiplicity in the absence of both αβ and γδ T-cells. This study demonstrates that altered T-cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and forms the basis for future mechanistic studies.

Histopathology of gill, muscle, intestine, kidney, and liver on Myxobolus sp.-infected Koi carp (Cyprinus carpio).

PubMed

Maftuch, Maftuch; Sanoesi, Ellana; Farichin, Ichfat; Saputra, Bagus Amin; Ramdhani, Luqman; Hidayati, Sarifa; Fitriyah, Nurul; Prihanto, Asep A

2018-03-01

This research aims to investigate the clinical symptoms of Myxobolus sp.-infected Koi carp ( Cyprinus carpio ) and to observe fish histopathology including histological alteration in the intestine, kidney, and liver organs. Descriptive method was employed in this research. The fish sample was obtained from Fish Farmer Group at Nglegok Village in Blitar City. The main observed parameters were the alteration of intestine, kidney, and liver of Koi infected with Myxobolus sp. parasite. The observation result of the histopathology of the parasite-infected fish indicated that necrosis and cyst occurred in the intestine. Necrosis also occurred in kidney, while hyaline degeneration occurred in tubule cells. Furthermore, necrosis and inflammation were also found in liver. It is obvious from the result that Myxobolus sp. infection resulted in the damage of Koi carp vital organs.

Physiology of Intestinal Absorption and Secretion

PubMed Central

Kiela, Pawel R.; Ghishan, Fayez K.

2016-01-01

Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipidand water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms. PMID:27086882

A retrospective audit on usage of Diatrizoate Meglumine (Gastrografin®) for intestinal obstruction or constipation in patients with advanced neoplasms.

PubMed

Heng, Sharon; Hardy, Janet; Good, Phillip

2018-01-01

Intestinal obstruction and constipation are common conditions in patients with advanced neoplasms. Diatrizoate Meglumine has been used in the management of both these conditions without good quality evidence of its effectiveness and safety. This audit aimed to assess the usage, effectiveness and adverse effects of Diatrizoate Meglumine for intestinal obstruction and constipation in patients with advanced neoplasms. A retrospective chart review was undertaken. Descriptive statistics were utilised. All patients with known advanced neoplasms admitted to Mater Health Services and St Vincent's Private Hospital Brisbane between January 2013 and October 2015; who were administered Diatrizoate Meglumine were included. Seventy-one patients received Diatrizoate Meglumine. The most common diagnoses were ovarian or primary peritoneal neoplasms (33.8%). Diatrizoate Meglumine was most commonly used for intestinal obstruction (59.2%). The median dose used per patient episode was 50 mL (range: 15-500 mL). Thirty-two patients (45%) had imaging 4-24 h post-dose with Diatrizoate Meglumine being present in the large intestine in 75% of these images. Intestinal obstruction or constipation resolved in 90% of patients post-dose. Most clinicians used 50 mL of Diatrizoate Meglumine as a single dose and repeated imaging after 4-24 h. Diatrizoate Meglumine was well tolerated and may be effective in resolving intestinal obstruction and constipation in patients with advanced neoplasms. Quality controlled studies are needed to further guide the use of Diatrizoate Meglumine in intestinal obstruction and constipation in patients with advanced neoplasms.

Cholesterol auxotrophy and intolerance to ezetimibe in mice with SREBP-2 deficiency in the intestine.

PubMed

Rong, Shunxing; McDonald, Jeffrey G; Engelking, Luke J

2017-10-01

SREBP-2 activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in the intestine, we generated a mouse model ( Vil-BP2 -/- ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2 -/- mice had reduced expression of genes required for sterol synthesis, in vivo sterol synthesis rates, and epithelial cholesterol contents. On a cholesterol-free diet, the mice displayed chronic enteropathy with histological abnormalities of both villi and crypts, growth restriction, and reduced survival that was prevented by supplementation of cholesterol in the diet. Likewise, SREBP-2-deficient enteroids required exogenous cholesterol for growth. Blockade of luminal cholesterol uptake into enterocytes with ezetimibe precipitated acutely lethal intestinal damage in Vil-BP2 -/- mice, highlighting the critical interplay in the small intestine of sterol absorption via NPC1L1 and sterol synthesis via SREBP-2 in sustaining the intestinal mucosa. These data show that the small intestine requires SREBP-2 to drive cholesterol synthesis that sustains the intestinal epithelia when uptake of cholesterol from the gut lumen is not available, and provide a unique example of cholesterol auxotrophy expressed in an intact, adult mammal. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Histopathologic characteristics of gastric adenocarcinoma in Mexican patients: a 10-year experience at the Hospital Juárez of Mexico.

PubMed

Martínez-Galindo, M G; Zamarripa-Dorsey, F; Carmona-Castañeda, A; Angeles-Labra, A; Peñavera-Hernández, R; Ugarte-Briones, C; Blanco-Vela, C I

2015-01-01

Gastric cancer is the second cause of death by cancer worldwide. Histologic classification may predict tumor biology, clinical behavior, and outcome. According to the Lauren classification, the disease is divided into 2 types, diffuse and intestinal, and the latter has a better prognosis. To determine the frequency of gastric adenocarcinoma and compare the histopathologic characteristics of intestinal and diffuse-type gastric adenocarcinoma in Mexican patients treated at a tertiary referral hospital. A retrospective study evaluated the pathology reports of patients with gastric adenocarcinoma corresponding to the time frame of January 2003 to December 2012. Adenocarcinomas of the gastric cardia were excluded. Frequencies were expressed as percentages and the categorical variables were compared with the chi-square test. Statistical significance was set at a P<.05. A total of 417 cases of gastric adenocarcinoma were found, 230 (55.2%) of which were diffuse-type and 118 (28.2%) were intestinal-type. The mean age of the patients with diffuse type gastric cancer was 54.02±14.93 and 119 (51.3%) of those patients were men. The mean age of the patients with intestinal-type gastric cancer was 63.43±13.78, and 69 (62.2%) were men. Ninety-two of the diffuse-type patients were under the age of 50 years, compared with 22 of the patients with intestinal-type carcinoma. This is the first study on the Mexican population to analyze the differences in the histologic types of adenocarcinoma. Diffuse-type gastric carcinoma was the most frequent subtype in our study population and it is associated with worse outcome. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

PubMed

Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

2009-02-01

Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic fibroblast growth factor.

PubMed

Hirai, Kenjiro; Tabata, Yasuhiko; Hasegawa, Suguru; Sakai, Yoshiharu

2016-10-01

Anastomotic leakage is a common complication of intestinal surgery. In an attempt to resolve this issue, a promising approach is enhancement of anastomotic wound healing. A method for controlled release of basic fibroblast growth factor (bFGF) using a gelatin hydrogel was developed with the objective of investigating the effects of this technology on intestinal anastomotic healing. The small intestine of Wistar rats was cut, end-to-end anastomosis was performed and rats were divided into three groups: bFGF group (anastomosis wrapped with a hydrogel sheet incorporating bFGF), PBS group (wrapped with a sheet incorporating phosphate-buffered saline solution) and NT group (no additional treatment). Degradation profiles of gelatin hydrogels in vivo and histological examinations were performed using gelatin hydrogels with various water contents and bFGF concentrations to define the optimal bFGF dose and hydrogel biodegradability. The anastomotic wound healing process was evaluated by histological examinations, adhesion-related score and bursting pressure. The optimal water content of the hydrogel and bFGF dose was determined as 96% and 30 µg per sheet, respectively. Application of bFGF significantly enhanced neovascularization, fibroblast infiltration and collagen production around the anastomotic site when compared with the other groups. Bursting pressure was significantly increased in the bFGF group. No significant difference was observed in the adhesion-related score among the groups and no anastomotic obstruction and leakage were observed. Therefore controlled release of bFGF enhanced healing of an intestinal anastomosis during the early postoperative period and is a promising method to suppress anastomotic leakage. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

IKKε and TBK1 expression in gastric cancer.

PubMed

Lee, Seung Eun; Hong, Mineui; Cho, Junhun; Lee, Jeeyun; Kim, Kyoung-Mee

2017-03-07

Inhibitor of kappa B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKKε and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKKε and TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKKε and TBK1 in gastric cancer and their role in prognosis have not been studied.To investigate overexpression of the IKKε and TBK1 proteins in gastric cancer and their relationship with clinicopathologic factors, we performed immunohistochemical staining using a tissue microarray. Tissue microarray samples were obtained from 1,107 gastric cancer patients who underwent R0 gastrectomy with extensive lymph node dissection and adjuvant chemotherapy.We identified expression of IKKε in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKε and TBK1 was identified in 1.5% of cases. Co-expression of IKKε and TBK1 was associated with differentiated intestinal histology and earlier T stage. In a multivariate binary logistic regression model, intestinal histologic type by Lauren classification and early AJCC stage were significant predictors for expression of IKKε and TBK1 proteins in gastric cancer. Changes in IKKε and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKKε and TBK1 should be considered in selected patients with intestinal-type gastric cancer.In conclusion, this is the first large-scale study investigating the relationships between expression of IKKε and TBK1 and clinicopathologic features of gastric cancer. The role of IKKε and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation.

Acellular porcine intestinal submucosa as fascial graft in an animal model: applications for revision tympanoplasty.

PubMed

Ort, Stuart A; Ehrlich, H Paul; Isaacson, Jon E

2010-09-01

To demonstrate regeneration of muscle fascia appropriate for future harvest with the use of acellular porcine intestinal submucosa in a rat model. Animal cohort study. Tertiary care academic medical center. Sixteen male Sprague-Dawley rats underwent excision of rectus abdominis muscle fascia. A sheet of acellular porcine intestinal submucosa was placed in the fascia harvest defect. Graft and underlying muscle were harvested at three-, six-, and nine-week intervals. Histologic examination, including immunohistology for anti-von Willebrand factor, was performed at each timepoint. Additional selected specimens were subjected to latex vascular perfusion casts to examine vessel growth patterns within the graft. Gross examination revealed a new tissue plane, indistinguishable from surrounding native fascia. Histology revealed an initial inflammatory response within the graft. Progressive influx of native tissue was noted over successive timepoints. Via collagen-specific staining, we noted progressive reorganization and maturation of the graft collagen matrix. At the final nine-week time point, a new loose connective tissue plane was reestablished between the graft and underlying muscle. Immunohistochemistry and latex perfusion both demonstrate an initial development of small capillaries that progresses over time to greater organization and arteriole formation. Fascia regeneration may be possible with use of an acellular porcine intestinal submucosa graft in an animal model. Future studies may prove beneficial in restoring fascia in humans. Implications for potential advantages in tympanoplasty are discussed. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Development of a 3D printed device to support long term intestinal culture as an alternative to hyperoxic chamber methods.

PubMed

Costa, Matheus O; Nosach, Roman; Harding, John C S

2017-01-01

Most interactions between pathogenic microorganisms and their target host occur on mucosal surfaces of internal organs such as the intestine. In vitro organ culture (IVOC) provides an unique tool for studying host-pathogen interactions in a controlled environment. However, this technique requires a complex laboratory setup and specialized apparatus. In addition, issues arise when anaerobic pathogens are exposed to the hyperoxic environment required for intestinal culture. The objective of this study was to develop an accessible 3D-printed device that would allow manipulation of the gas mixture used to supply the tissue culture media separately from the gas mixture exposed to the mucosal side of explants. Porcine colon explants from 2 pigs were prepared ( n  = 20) and cultured for 0h, 8h, 18h and 24h using the device. After the culture period, explants were fixed in formalin and H&E stained sections were evaluated for histological defects of the mucosa. At 8h, 66% of samples displayed no histological abnormalities, whereas samples collected at 18h and 24h displayed progressively increasing rates of superficial epithelial erosion and epithelial metaplasia. The 3D-design reported here allows investigators to setup intestinal culture explants while manipulating the gas media explants are exposed to, to support tissue viability for a minimal of 8h. The amount of media necessary and tissue contamination are potential issues associated with this apparatus.

Validation of Donor-Specific Tolerance of Intestinal Transplant by a Secondary Heart Transplantation Model.

PubMed

Pengcheng, Wang; Xiaosong, Li; Xiaofeng, Li; Zhongzhi, Li

2017-02-01

It is well accepted that survival after a second organ transplant without immunosuppressive agents indicates tolerance for the first transplant. To validate donor-specific tolerance, we established a rat model with a secondary heart transplant after intestinal transplant, which has so far not been described in the literature. We transplanted intestine from Fischer F344 rats to Lewis rats orthotopically. Lewis rats received tacrolimus pretreatment before transplant and a 14-day course of rapamycin 1 month after transplant. At 120 days after primary intestinal transplant, hearts from 6 F344 rats (group A) or 6 Brown Norway rats (group B) were transplanted to Lewis rats that had survived intestinal transplant and without additional immunosuppressive agents. We analyzed survival data, histologic changes, cells positive for the ED1 macrophage marker in transplanted hearts, and 3 lymphocyte levels in both groups. Thirty days after secondary heart transplant, group A hearts were continuously beating; however, group B hearts stopped beating at around 10 days after transplant (8.5 ± 1.5 d; P < .05). Our histologic study showed that both groups had muscle damage and cellular infiltration in hearts that were distinctly different from normal hearts, with ED1-positive cells counted in both groups (85 ± 16 in group A, 116 ± 28 in group B; P > .05). Fluorescence-activated cell sorting showed that CD4/CD25-positive regulatory T cell, CTLA4/CD4/CD25-positive regulatory T cell, and Natural killer T-cell levels were significantly higher level in group A versus B (P < .05). The donor-specific tolerance that we observed was possibly a state of "clinical tolerance" rather than "immunologic tolerance." Our rat model is a feasible and reliable model to study donor-specific tolerance. The higher levels of lymphocytic T cells shown in intestinal transplant recipients were associated with longer allograft survival, possibly contributing to donor-specific tolerance.

Comparison of different histological protocols for the preservation and quantification of the intestinal mucus layer in pigs.

PubMed

Röhe, Ilen; Hüttner, Friedrich Joseph; Plendl, Johanna; Drewes, Barbara; Zentek, Jürgen

2018-02-05

The histological characterization of the intestinal mucus layer is important for many scientific experiments investigating the interaction between intestinal microbiota, mucosal immune response and intestinal mucus production. The aim of this study was to examine and compare different fixation protocols for displaying and quantifying the intestinal mucus layer in piglets and to test which histomorphological parameters may correlate with the determined mucus layer thickness. Jejunal and colonal tissue samples of weaned piglets (n=10) were either frozen in liquid nitrogen or chemically fixed using methacarn solution. The frozen tissue samples were cryosectioned and subsequently postfixed using three different postfixatives: paraformaldehyde vapor, neutrally buffered formalin solution and ethanol solution. After dehydration, methacarn fixed tissues were embedded in paraffin wax. Both sections of cryopreserved and methacarn fixed tissue samples were stained with Alcian blue (AB)-PAS followed by the microscopically determination of the mucus layer thickness. Different pH values of the Alcian Blue staining solution and two mucus layer thickness measuring methods were compared. In addition, various histomorphological parameters of methacarn fixed tissue samples were evaluated including the number of goblet cells and the mucin staining area. Cryopreservation in combination with chemical postfixation led to mucus preservation in the colon of piglets allowing mucus thickness measurements. Mucus could be only partly preserved in cryosections of the jejunum impeding any quantitative description of the mucus layer thickness. The application of different postfixations, varying pH values of the AB solution and different mucus layer measuring methods led to comparable results regarding the mucus layer thickness. Methacarn fixation proved to be unsuitable for mucus depiction as only mucus patches were found in the jejunum or a detachment of the mucus layer from the epithelium was observed in the colon. Correlation analyses revealed that the proportion of the mucin staining area per crypt area (relative mucin staining) measured in methacarn fixed tissue samples corresponded to the colonal mucus layer thickness determined in cryopreserved tissue samples. In conclusion, the results showed that cryopreservation using liquid nitrogen followed by chemical postfixation and AB-PAS staining led to a reliable mucus preservation allowing a mucus thickness determination in the colon of pigs. Moreover, the detected relative mucin staining area may serve as a suitable histomorphological parameter for the assessment of the intestinal mucus layer thickness. The findings obtained in this study can be used for the implementation of an improved standard for the histological description of the mucus layer in the colon of pigs.

How to treat an extensive form of primary intestinal lymphangiectasia?

PubMed

Troskot, Rosana; Jurčić, Dragan; Bilić, Ante; Gomerčić Palčić, Marija; Težak, Stanko; Brajković, Ivana

2015-06-21

We report a case of a 42-year-old man with a rare disorder known as primary intestinal lymphangiectasia, which is characterized by dilated intestinal lymphatics that lead to the development of protein-losing enteropathy. The patient presented with a grand mal seizure caused by malabsorption-derived electrolytes and a protein disorder. Signs of the disease, including chronic diarrhea and peripheral edema, manifested 10 years ago, but a diagnosis was never made. The diagnosis was suspected because of the clinical manifestations, laboratory tests, imaging and endoscopic findings. Hyperemic and edematous mucosa of the small intestine corresponded to scattered white spots with dilated intestinal lymphatics and whitish villi in the histological specimen of the biopsied jejunal mucosa. Although numerous therapeutic strategies are available, only octreotide therapy proved to be an effective means of therapeutic resolution in this patient. Although the patient had a partial remission following the use of a slow release formula of octreotide, his prognosis, clinical course, and future treatment challenges are yet to be determined.

How to treat an extensive form of primary intestinal lymphangiectasia?

PubMed Central

Troskot, Rosana; Jurčić, Dragan; Bilić, Ante; Gomerčić Palčić, Marija; Težak, Stanko; Brajković, Ivana

2015-01-01

We report a case of a 42-year-old man with a rare disorder known as primary intestinal lymphangiectasia, which is characterized by dilated intestinal lymphatics that lead to the development of protein-losing enteropathy. The patient presented with a grand mal seizure caused by malabsorption-derived electrolytes and a protein disorder. Signs of the disease, including chronic diarrhea and peripheral edema, manifested 10 years ago, but a diagnosis was never made. The diagnosis was suspected because of the clinical manifestations, laboratory tests, imaging and endoscopic findings. Hyperemic and edematous mucosa of the small intestine corresponded to scattered white spots with dilated intestinal lymphatics and whitish villi in the histological specimen of the biopsied jejunal mucosa. Although numerous therapeutic strategies are available, only octreotide therapy proved to be an effective means of therapeutic resolution in this patient. Although the patient had a partial remission following the use of a slow release formula of octreotide, his prognosis, clinical course, and future treatment challenges are yet to be determined. PMID:26109821

A confusing world: what to call histology of three-dimensional tumour margins?

PubMed

Moehrle, M; Breuninger, H; Röcken, M

2007-05-01

Complete three-dimensional histology of excised skin tumour margins has a long tradition and, unfortunately, a multitude of names as well. Mohs, who introduced it, called it 'microscopically controlled surgery'. Others have described it as 'micrographic surgery', 'Mohs' micrographic surgery', or simply 'Mohs' surgery'. Semantic confusion became truly rampant when variant forms, each useful in its own way for detecting subclinical outgrowths of malignant skin tumours, were later introduced under such names as histographic surgery, systematic histologic control of the tumour bed, histological control of excised tissue margins, the square procedure, the perimeter technique, etc. All of these methods are basically identical in concept. All involve complete, three-dimensional histological visualization and evaluation of excision margins. Their common goal is to detect unseen tumour outgrowths. For greater clarity, the authors of this paper recommend general adoption of '3D histology' as a collective designation for all the above methods. As an added advantage, 3D histology can also be used in other medical disciplines to confirm true R0 resection of, for example, breast cancer or intestinal cancer.

Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol.

PubMed

Kirpich, Irina A; Feng, Wenke; Wang, Yuhua; Liu, Yanlong; Beier, Juliane I; Arteel, Gavin E; Falkner, K Cameron; Barve, Shirish S; McClain, Craig J

2013-05-01

Alcohol and dietary fat both play an important role in alcohol-mediated multi-organ pathology, including gut and liver. In the present study we hypothesized that the combination of alcohol and dietary unsaturated fat (USF) would result in intestinal inflammatory stress and mucus layer alterations, thus contributing to disruption of intestinal barrier integrity. C57BL/6N mice were fed Lieber-DeCarli liquid diets containing EtOH and enriched in USF (corn oil/linoleic acid) or SF (medium chain triglycerides: beef tallow) for 8 weeks. Intestinal histology, morphometry, markers of inflammation, as well as levels of mucus protective factors were evaluated. Alcohol and dietary USF triggered an intestinal pro-inflammatory response, characterized by increase in Tnf-α, MCP1, and MPO activity. Further, alcohol and dietary USF, but not SF, resulted in alterations of the intestinal mucus layer, characterized by decreased expression of Muc2 in the ileum. A strong correlation was observed between down-regulation of the antimicrobial factor Cramp and increased Tnf-α mRNA. Therefore, dietary unsaturated fat (corn oil/LA enriched) is a significant contributing factor to EtOH-mediated intestinal inflammatory response and mucus layer alterations in rodents. Copyright © 2013 Elsevier Inc. All rights reserved.

Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan

2015-01-02

Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudinsmore » were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.« less

Compared with Raw Bovine Meat, Boiling but Not Grilling, Barbecuing, or Roasting Decreases Protein Digestibility without Any Major Consequences for Intestinal Mucosa in Rats, although the Daily Ingestion of Bovine Meat Induces Histologic Modifications in the Colon.

PubMed

Oberli, Marion; Lan, Annaïg; Khodorova, Nadezda; Santé-Lhoutellier, Véronique; Walker, Francine; Piedcoq, Julien; Davila, Anne-Marie; Blachier, François; Tomé, Daniel; Fromentin, Gilles; Gaudichon, Claire

2016-08-01

Cooking may impair meat protein digestibility. When undigested proteins are fermented by the colon microbiota, they can generate compounds that potentially are harmful to the mucosa. This study addressed the effects of typical cooking processes and the amount of bovine meat intake on the quantity of undigested proteins entering the colon, as well as their effects on the intestinal mucosa. Male Wistar rats (n = 88) aged 8 wk were fed 11 different diets containing protein as 20% of energy. In 10 diets, bovine meat proteins represented 5% [low-meat diet (LMD)] or 15% [high-meat diet (HMD)] of energy, with the rest as total milk proteins. Meat was raw or cooked according to 4 processes (boiled, barbecued, grilled, or roasted). A meat-free diet contained only milk proteins. After 3 wk, rats ingested a (15)N-labeled meat meal and were killed 6 h later after receiving a (13)C-valine injection. Meat protein digestibility was determined from (15)N enrichments in intestinal contents. Cecal short- and branched-chain fatty acids and hydrogen sulfide were measured. Intestinal tissues were used for the assessment of protein synthesis rates, inflammation, and histopathology. Meat protein digestibility was lower in rats fed boiled meat (94.5% ± 0.281%) than in the other 4 groups (97.5% ± 0.0581%, P < 0.001). Cecal and colonic bacterial metabolites, inflammation indicators, and protein synthesis rates were not affected by cooking processes. The meat protein amount had a significant effect on cecal protein synthesis rates (LMD > HMD) and on myeloperoxidase activity in the proximal colon (HMD > LMD), but not on other outcomes. The ingestion of bovine meat, whatever the cooking process and the intake amount, resulted in discrete histologic modifications of the colon (epithelium abrasion, excessive mucus secretion, and inflammation). Boiling bovine meat at a high temperature (100°C) for a long time (3 h) moderately lowered protein digestibility compared with raw meat and other cooking processes, but did not affect cecal bacterial metabolites related to protein fermentation. The daily ingestion of raw or cooked bovine meat had no marked effect on intestinal tissues, despite some slight histologic modifications on distal colon. © 2016 American Society for Nutrition.

Primary intestinal lymphangiectasia with generalized warts.

PubMed

Lee, Soon Jae; Song, Hyun Joo; Boo, Sun-Jin; Na, Soo-Young; Kim, Heung Up; Hyun, Chang Lim

2015-07-21

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient.

Primary intestinal lymphangiectasia with generalized warts

PubMed Central

Lee, Soon Jae; Song, Hyun Joo; Boo, Sun-Jin; Na, Soo-Young; Kim, Heung Up; Hyun, Chang Lim

2015-01-01

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient. PMID:26217101

Intravenous acid fibroblast growth factor protects intestinal mucosal cells against ischemia-reperfusion injury via regulating Bcl-2/Bax expression.

PubMed

Chen, Wei; Fu, Xiao-Bing; Ge, Shi-Li; Sun, Tong-Zhu; Zhou, Gang; Han, Bing; Du, Yi-Ri; Li, Hai-Hong; Sheng, Zhi-Yong

2005-06-14

To detect the effect of acid fibroblast growth factor (aFGF) on apoptosis and gene expression of bax and bcl-2 gene in rat intestine after ischemia/reperfusion (I/R) injury, and to explore the protective mechanisms of aFGF. One hundred and eight Wistar rats were randomly divided into sham-operated control group (C) (n = 6), intestinal ischemia group (I) (n = 6), aFGF treatment group (A) (n = 48) and intestinal ischemia-reperfusion group (R) (n = 48). In group I, the animals were killed after 45 min of superior mesenteric artery (SMA) occlusion, while in groups R and A, the rats sustained 45 min of SMA occlusion and were then treated with normal saline and aFGF, respectively, sustained 15 min, 30 min, 1, 2, 6, 12, 24, or 48 h of reperfusion, respectively. In group C, SMA was separated, but without occlusion. Apoptosis in intestinal villus was determined with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken not only for detection of bax and bcl-2 gene expression by RT-PCR, but also for detection of bax and bcl-2 protein expression and distribution by immunohistochemical analysis. The rat survival rates in aFGF treated group were higher than group R (P<0.05) and the improvement of intestinal histological structures was observed at 2, 6, and 12 h after the reperfusion in group A compared with group R. The apoptotic rates were (41.17+/-3.49)%, (42.83+/-5.23)% and (53.33+/-6.92)% at 2, 6 and 12 h after reperfusion, respectively in group A, apparently less than those of group R at matched time points (50.67+/-6.95, 54.17+/-7.86, 64.33+/-6.47, respectively) (P<0.05). The bax gene transcription and translation were significantly decreased in group A vs group R, while mRNA and protein contents of Bcl-2 in group A were obviously higher than those in group R during 2-12 h period after reperfusion. The changes in histological structure and the increment of apoptotic rate indicated that the intestinal barrier was damaged after intestinal I/R injury, whilst intravenous aFGF could alleviate apoptosis induced by ischemia and reperfusion in rat intestinal tissues, in which genes of bax and bcl-2 might play important roles.

[Protein-losing enteropathy due to intestinal lymphangiectasis: a rare disease. Report of two cases].

PubMed

Sommaruga, Horacio; Santarcángelo, Salomé Catalina; Quintana, Carlos; Navacchia, Daniel

2015-03-01

Congenital intestinal lymphangiectasis (LIP) is a protein-losing enteropathy that appears sporadically in children. It begins with edema due to hypoproteinemia and hypoalbuminemia, and in some cases with ascites, immunodeficience and hypocalcemic tetania. The purpose of this report is to present two patients with LIP which appeared during the first year of life. The diagnosis was certificated by upper gastrointestinal videoendoscopy and histological findings. Both patients were treated with a new formula containing mean chain triglycerides with an adequate response, not obtained before with a common semielemental formula.

Histopathological effects of carbaryl on digestive system of snake-eyed lizard, Ophisops elegans.

PubMed

Cakici, Ozlem; Akat, Esra

2012-05-01

We examined the effects of carbaryl in the digestive system of Ophisops elegans. Lizards were exposed once to different concentrations of carbaryl (2.5, 25 and 250 μg/g). After 96 h, findings related to the esophagus in all treatment groups were not conspicuous. The most important histological defects were observed in the stomach. In the small intestine, collapse of villi was prominent at high-dose. In the large intestine, disintegration in epithelial cells and scattered secretory granules of goblet cells were observed at high dose.

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

PubMed Central

Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

2012-01-01

Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

Effects of methanolic extract from leaves of Rubus imperialis in DSS-induced colitis in mice.

PubMed

da Silva, Luisa Mota; Somensi, Lincon Bordignon; Boeing, Thaise; Barp, Cristiane; Cechinel-Filho, Valdir; Niero, Rivaldo; de Andrade, Sérgio Faloni

2016-12-01

This study investigated the effects of Rubus imperialis, a berry known as "amora-branca", in colitis dextran sulfate sodium (DSS)-induced in mice. Animals were treated orally with vehicle (water), 5-aminosalicylic acid (100 mg/kg) or methanolic extract from leaves of R. imperialis (MERI, 100 mg/kg), once a day during seven days. The disease activity index (DAI) was observed daily. Colons were collected for histological, histochemical and biochemical analysis. The administration of MERI exacerbated colitis, as indicated by DAI heightened weight loss and increased histological colonic injury. MERI also decreased the colon mucin levels and increased colonic TNF content. The colonic levels of reduced glutathione and the superoxide dismutase activity in colitic group treated with MERI were decreased. Despite the worsening of colitis, MERI not altered the intestinal transit, body weight, colon length or organs weight in normal mice. Tormentic acid (TA) and 2β,3β,19α-trihydroxyursolic acid (THA), compounds isolated from MERI, reduced the L929 cells viability. Thus, MERI may have aggravated the DSS-induced colitis through intense intestinal mucus barrier impairment, which would lead to inflammatory responses, TA and THA contribute to the intestinal damage verified suggesting caution about the use of R. imperialis preparations, particularly in inflammatory bowel diseases.

Colloid vs. crystalloid infusions in gastrointestinal surgery and their different impact on the healing of intestinal anastomoses.

PubMed

Marjanovic, Goran; Villain, Christian; Timme, Sylvia; zur Hausen, Axel; Hoeppner, Jens; Makowiec, Frank; Holzner, Philipp; Hopt, Ulrich Theodor; Obermaier, Robert

2010-04-01

The aim of this study was to investigate if colloid infusions have different effects on intestinal anastomotic healing when compared to crystalloid infusions depending on the amount of the administered volume. Twenty-eight Wistar rats were randomly assigned to four groups receiving different amounts of either a crystalloid (Cry) or a colloid (Col) infusion solution. Animals with volume restriction (Cry (-) or Col (-)) were treated with a low and animals with volume overcharge (Cry (+) or Col (+)) with a high flow rate. All animals received an infusion for a 60-min period, while an end-to-end small bowel anastomosis was performed. At reoperation, the anastomotic bursting pressure (millimeters of mercury) was measured, as well as anastomotic hydroxyproline concentration. The presence of bowel wall edema was assessed histologically. Median bursting pressures were comparable in the Col (-) [118 mm Hg (range 113-170)], the Cry (-) [118 mm Hg (78-139)], and the Col (+) [97 mm Hg (65-152)] group. A significantly lower median bursting pressure was found in animals with crystalloid volume overload Cry (+) [73 mm Hg (60-101)]. Corresponding results were found for hydroxyproline concentration. Histology revealed submucosal edema in Cry (+) animals. In case of a fixed, high-volume load, colloids seem to have benefits on intestinal anastomotic healing when compared to crystalloid infusions.

Serum albumin level during intestinal exfoliative rejection: a potential predictor of graft recovery and patient outcome.

PubMed

Zambernardi, Agustina; Gondolesi, Gabriel; Cabanne, Ana; Martinez, María I; Solar, Héctor; Rumbo, Martín; Rumbo, Carolina

2013-01-01

Exfoliative rejection is a severe complication after intestinal transplant. The assessment of mucosa histology is restricted to the area reached by endoscopy. We aim to evaluate the serum albumin (SA) value as a parameter of graft damage and clinical prognosis in intestinal exfoliative rejection (ExR). The present study is a retrospective analysis of 11 episodes of ExR occurred in a cohort of 26 patients. SA levels were measured 24 h after diagnosis and twice a week thereafter and then correlated with parameters of clinical and graft histological recovery (HR). During ExR, all patients had very low SA levels, reaching a minimum average of 1.9 ± 0.3 g/dL. According to the value of albumin levels at ExR diagnosis, the patients were grouped finding a correlation with their clinical evolution. Six ExR episodes presented with severe hipoalbuminemia (<2.2 g/dL; p < 0.05) that correlated with worse patient and graft outcome, ranging from graft loss and need for re-transplantation to delayed clinical and HR. SA at ExR diagnosis may be an indicator of the severity of the ExR process, and it could also be used as an early predictor of patient and graft outcome. © 2013 John Wiley & Sons A/S.

[Histological changes of gastric atrophy and intestinal metaplasia after Helicobacter pylori eradication].

PubMed

Lee, Yonggu; Jeon, Yong Cheol; Koo, Tai Yeon; Cho, Hyun Seok; Byun, Tae Jun; Kim, Tae Yeob; Lee, Hang Lak; Eun, Chang Soo; Lee, Oh Young; Han, Dong Soo; Sohn, Joo Hyun; Yoon, Byung Chul

2007-11-01

Long-term Helicobater pylori infection results in atrophic gastritis and intestinal metaplasia, and increases the risk of gastric cancer. However, it is still controversial that eradication of H. pylori improves atrophy or metaplasia. Therefore, we investigated histological changes after the H. pylori eradication in patients with atrophy or metaplasia. One hundred seven patients who received successful eradication of H. pylori infection in Hanyang University, Guri Hospital from March 2001 to April 2006, were enrolled. Antral biopsy was taken before the eradication to confirm the H. pylori infection and grade of atrophy or metaplasia by updated Sydney System. After a certain period of time, antral biopsy was repeatedly taken to confirm the eradication and investigate histological changes of atrophy or metaplasia. Mean age of the patients was 55.3+/-11.3, and average follow-up period was 28.7+/-13.9 months. Endoscopic diagnosis included gastric ulcer, duodenal ulcer, non-ulcer antral gastritis. Atrophy was observed in 41 of 91 and their average score was 0.73+/-0.92. After the eradication of H. pylori, atrophy was improved (0.38+/-0.70, p=0.025). However, metaplasia which was observed in 49 of 107, did not significantly improve during the follow-up period. Newly developed atrophy (7 of 38) or metaplasia (18 of 49) was observed in patients who without atrophy or metaplasia initially. Their average scores were slightly lower than those of cases with pre-existing atrophy or metaplasia without statistical significance. After the eradication of H. pylori infection, atrophic gastritis may be improved, but change of intestinal metaplasia is milder and may take longer duration for improvement.

Investigation and control of an attaching and effacing Escherichia coli outbreak in a colony of captive budgerigars (Melopsittacus undulatus).

PubMed

Seeley, Kathryn E; Baitchman, Eric; Bartlett, Susan; DebRoy, Chitrita; Garner, Michael M

2014-12-01

An increase in mortality in a captive flock of budgerigars (Melopsittacus undulatus) coincided with the isolation of attaching and effacing Escherichia coli from postmortem samples. Common histologic lesions included hepatitis, enteritis, and in one case attaching and effacing lesions along the intestinal tract. Retrospective review of necropsy records and increased sampling led to the identification of several cases of E. coli with the attaching and effacing (eae) virulence gene. Factors such as environment, nutrition, and concomitant pathogens were thought to contribute to mortality in the flock. Although it is not clear whether E. coli was a primary pathogen during the period of increased mortality, the presence of the eae gene combined with associated histologic lesions supports the conclusion that this organism was a significant contributor to mortality. Manipulation of diet, environment, and the addition of probiotic supplementation resulted in a decline in mortality rate and decreased shedding of E. coli based on negative follow-up cultures of intestines, liver, and feces.

[A case of a perivascular epithelioid cell tumor mimicking colon cancer].

PubMed

Cho, Young Whan; Kim, Kyung Jo; Ye, Byong Duk; Byeon, Jeong Sik; Myung, Seung Jae; Yang, Suk Kyun; Kim, Jin Ho

2012-12-01

Perivascular epithelioid cell tumor (PEComa) is extremely rare, which originated from mesenchymal cells in the intestine, and composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. We report here on a case of PEComa in the sigmoid colon. A 62-year-old woman presented with hematochzia 10 days ago. Her abdominal computed tomography scan showed a 5 cm sized intraluminal fungating heterogeneously enhanced, high density mass, which infiltrated pericolic tissue surrounding the sigmoid colon. Colonoscopy showed a purple colored polypoid mass with lobulating contour in the sigmoid colon. She underwent laparoscopic anterior resection. On the histologic examination, the tumor consisted of polygonal epithelioid cells with sheet-like growth of nests, which looked like alveolar tissues in lung. The tumor cells were strongly positive stained with human melanoma black-45 (HMB-45). Pathologic examination was compatible with PEComa. Sixteen months after surgery, she did well without tumor recurrence after surgery. We review the literatures concerning PEComa of the intestine focusing on endoscopic findings.

Study of MET protein levels and MET gene copy number in 72 sinonasal intestinal-type adenocarcinomas.

PubMed

Projetti, Fabrice; Mesturoux, Laura; Coulibaly, Béma; Durand, Karine; Chaunavel, Alain; Léobon, Sophie; Gadeaud, Emilie; Caire, François; Bessède, Jean-Pierre; Labrousse, François

2015-11-01

Sinonasal intestinal-type adenocarcinomas (ITACs) have a poor prognosis, and are defined on the basis of their morphological similarities to colorectal adenocarcinomas. MET signaling pathway is involved in oncogenesis in various cancers. Nothing is currently known about the role of MET in ITACs. In a series of 72 ITACs, we investigated MET protein levels by immunohistochemistry (IHC) and gene copy number by in situ hybridization. These findings were analyzed as a function of clinical data, histological typing, and patient outcome. MET protein was overproduced in 64% of cases and chromosome 7 polysomy was observed in 52% of cases. No tumor displayed MET amplification. The presence of mucinous or solid histological components, T3/T4 tumors, and incomplete resection were associated with a poor outcome. MET is overproduced in about two third of ITACs, suggesting a role for the MET signaling pathway in the oncogenesis of these tumors. © 2014 Wiley Periodicals, Inc.

Wireless capsule endoscopy for diagnosis of acute intestinal graft-versus-host disease.

PubMed

Neumann, Susanne; Schoppmeyer, Konrad; Lange, Thoralf; Wiedmann, Marcus; Golsong, Johannes; Tannapfel, Andrea; Mossner, Joachim; Niederwieser, Dietger; Caca, Karel

2007-03-01

The small intestine is the most common location of intestinal graft-versus-host disease (GVHD). EGD with duodenal biopsies yields the highest diagnostic sensitivity, but the jejunum and ileum are not accessible by regular endoscopy. In contrast, wireless capsule endoscopy (WCE) is a noninvasive imaging procedure offering complete evaluation of the small intestine. The objective was to compare the diagnostic value of EGD, including biopsies, with the results of WCE in patients with acute intestinal symptoms who received allogeneic blood stem cell transplantation and to analyze the appearance and distribution of acute intestinal GVHD lesions in these patients. An investigator-blinded, single-center prospective study. Patients with acute intestinal symptoms after allogeneic stem cell transplantation underwent both EGD and WCE within 24 hours. Clinical data were recorded during 2 months of follow-up. Fourteen consecutive patients with clinical symptoms of acute intestinal GVHD were recruited. In 1 patient, the capsule remained in the stomach and was removed endoscopically. In 7 of 13 patients who could be evaluated, acute intestinal GVHD was diagnosed by EGD with biopsies, but 3 of these would have been missed by EGD alone. In all 7 patients with histologically confirmed acute intestinal GVHD, WCE revealed typical signs of GVHD. Lesions were scattered throughout the small intestine, but were most accentuated in the ileum. This study had a small number of patients. WCE, which is less invasive than EGD with biopsies, showed a comparable sensitivity and a high negative predictive value for diagnosing acute intestinal GVHD. It may be helpful to avoid repeated endoscopic procedures in patients who have undergone stem cell transplantation.

Extended intestinal metaplasia. A survey of 1392 gastrectomies from dwellers of the Pacific basin.

PubMed

Rubio, C A; Hirota, T; Itabashi, M; Mandai, K; Yanagisawa, A; Kitagawa, T; Sugano, H; Kato, Y

2004-01-01

To assess the extent of gastric intestinal metaplasia (IM) in gastrectomy specimens in populations of the Pacific basin having different incidence of gastric carcinoma. One thousand three hundred and nine-two gastrectomies were investigated: 1088 had a gastric carcinoma and 304 miscellaneous gastric diseases. Twenty-one thousand three hundred and fourteen histological sections were reviewed under low-power (4X). IM was either spotty (SIM) or extended (EIM= encompassing one or more entire low-power fields/section). Widespread IM (WIM) was regarded as EIM if present in > or =5 histological sections. The percent of gastrectomies harboring a carcinoma increased significantly with increasing age more notably in those with diffuse carcinomas (DC) than in those with intestinal carcinomas (IC). The percent of gastrectomies with EIM was significantly higher in specimens with IC than with DC, particularly among elderly patients, and in specimens from countries with a high cancer incidence. The percent of gastrectomies with WIM was higher in specimens having IC than in those having DC. Migration per se did not influence the frequency of specimens with EIM in elderly Japanese patients: Japanese migrants to Hawaii had a similarly high frequency of EIM as those dwelling in Japan. Japanese patients with a gastric carcinoma showed atypical mitoses in areas with EIM far from the tumor, suggesting that cellular mutation(s) play a role in the evolution of EIM towards gastric dysplasia and carcinoma in that ethnic group. The drawback of gastric biopsies in assessing the extent of gastric intestinal metaplasia and, thereby, estimating possible cancer risk in long-term studies has been stressed.

Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

PubMed

ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

2014-07-01

The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P < 0.05). The germinal centers of the lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

Is intestinal biopsy always needed for diagnosis of celiac disease?

PubMed

Scoglio, Riccardo; Di Pasquale, Giuseppe; Pagano, Giuseppe; Lucanto, Maria Cristina; Magazzù, Giuseppe; Sferlazzas, Concetta

2003-06-01

Intestinal biopsy is required for a diagnosis of celiac disease (CD). The aim of this study was to assess diagnostic accuracy of transglutaminase antibodies (TGA) in comparison and in association with that of antiemdomysial antibodies (AEA), calculating the post-test odds of having the disease, to verify whether some patients might avoid undergoing intestinal biopsy for a diagnosis of CD. A total of 181 consecutive patients (131 < 18 yr), referred to our celiac clinic by primary care physicians for suspect CD. Overall diagnostic accuracy, negative predictive value, and likelihood ratio (LR) were calculated both for each serological test and for serial testing (TGA and after AEA, assuming the post-test probability of TGA as pretest probability of AEA). Both serological determination and histological evaluation were blindly performed. Histology of duodenal mucosa was considered the gold standard. The overall accuracy of TGA and of AEA were 92.8% (89.1-96.6) and 93.4% (89.7-97.0), respectively. The negative predictive value of TGA and AEA were 97.2% (91.9-102.6) and 87.2% (77.7-96.8), respectively. Positive likelihood ratios for TGA and AEA were 3.89 (3.40-4.38) and 7.48 (6.73-8.23), respectively. Serial testing, in groups of patients with prevalence of CD estimated higher than 75%, such as those with classic symptoms of CD, would provide a post-test probability of more than 99%. Our results suggest that serial testing with TGA and AEA might allow, in some cases, the avoidance of intestinal biopsy to confirm the diagnosis of CD.

Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.

PubMed

Ji, Chen-Guang; Xie, Xiao-Li; Yin, Jie; Qi, Wei; Chen, Lei; Bai, Yun; Wang, Na; Zhao, Dong-Qiang; Jiang, Xiao-Yu; Jiang, Hui-Qing

2017-04-01

Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns.

PubMed

Vanoli, Alessandro; Di Sabatino, Antonio; Martino, Michele; Klersy, Catherine; Grillo, Federica; Mescoli, Claudia; Nesi, Gabriella; Volta, Umberto; Fornino, Daniele; Luinetti, Ombretta; Fociani, Paolo; Villanacci, Vincenzo; D'Armiento, Francesco P; Cannizzaro, Renato; Latella, Giovanni; Ciacci, Carolina; Biancone, Livia; Paulli, Marco; Sessa, Fausto; Rugge, Massimo; Fiocca, Roberto; Corazza, Gino R; Solcia, Enrico

2017-10-01

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis.

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

PubMed

Mills, Matthew N; Yang, George Q; Oliver, Daniel E; Liveringhouse, Casey L; Ahmed, Kamran A; Orman, Amber G; Laronga, Christine; Hoover, Susan J; Khakpour, Nazanin; Costa, Ricardo L B; Diaz, Roberto

2018-06-02

Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC. A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome. MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC. Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intestinal Mechanomorphological Remodeling Induced by Long-Term Low-Fiber Diet in Rabbits.

PubMed

Liu, Yue; Zhao, Jingbo; Liao, Donghua; Wang, Guixue; Gregersen, Hans

2017-12-01

Short-term feeding with low-fiber diet remodels the mechanomorphological properties in the rabbit small intestine. The aims were to study the effect of feeding low-fiber diet for 5 months on mechanomorphological properties including the collagen fraction in the rabbit intestines. Fifteen rabbits were divided into an Intervention group (IG, n = 10) fed a low-fiber diet and a Control group (CG, n = 5) fed a normal diet for 5 months. Five months later, four 10-cm-long segments obtained from the duodenum, jejunum, ileum and large intestine were used for histological and mechanical analysis, respectively. The wall thickness, wall area, mucosa and muscle layer thickness decreased whereas the submucosa layer thickness increased in the IG (p < 0.05). The collagen fraction decreased in all layers and segments in the IG (p < 0.05). The opening angle increased in the large intestine and decreased in the ileum in the IG (p < 0.05). The intestinal stress-strain curves for IG shifted to the right, indicating softening. The creep did not change in the four segments. The wall stiffness was associated with wall thickness and collagen fraction in the submucosa layer. Long-term low-fiber diet in rabbits induced histomorphometric and biomechanical remodelling of the intestines.

Establishing Caenorhabditis elegans as a model for Mycobacterium avium subspecies hominissuis infection and intestinal colonization

PubMed Central

Everman, Jamie L.; Ziaie, Navid R.; Bechler, Jessica; Bermudez, Luiz E.

2015-01-01

ABSTRACT The nematode Caenorhabditis elegans has become a model system for studying the disease interaction between pathogens and the host. To determine whether the transparent nematode could serve as a useful model for Mycobacterium avium subspecies hominissuis (MAH) infection of the intestinal tract, worms were fed MAH and assayed for the effects of the bacterial infection on the worm. It was observed during feeding that viable MAH increases in the intestinal lumen in a time dependent manner. Ingestion of MAH was deemed non-toxic to worms as MAH-fed populations have similar survival curves to those fed E. coli strain OP50. Pulse-chase analysis using E. coli strain OP50 revealed that MAH colonize the intestinal tract, as viable MAH remain within the intestine after the assay. Visualization of intestinal MAH using histology and transmission electron microscopy demonstrates that MAH localizes to the intestinal lumen, as well as establishes direct contact with intestinal epithelium. Bacterial colonization appears to have a detrimental effect on the microvilli of the intestinal epithelial cells. The MAH ΔGPL/4B2 strain with a mutation in glycopeptidolipid production is deficient in binding to human epithelial cells (HEp-2), as well as deficient in its ability to bind to and colonize the intestinal tract of C. elegans as efficiently as wild-type MAH. These data indicate the C. elegans may serve as a useful model system for MAH pathogenesis and in determining the mechanisms used by MAH during infection and colonization of the intestinal epithelium. PMID:26405050

Clinical and pathological observations on natural infections of cryptosporidiosis and flagellate protozoa in leopard geckos (Eublepharis macularius).

PubMed

Taylor, M A; Geach, M R; Cooley, W A

1999-12-11

A group of adult leopard geckos (Eublepharis macularius) which had been losing weight for several months were found to be infected with Cryptosporidium species. Histological and electron microscopical investigations on the intestines of five of the lizards revealed the presence of large numbers of the developmental stages of Cryptosporidium species attached to the mucosal surface of the lower intestine, and large numbers of flagellate protozoa, suspected to be predominantly Trichomonas species, in the gut lumen. The clinical signs were attributed to the presence of one or both types of parasites.

Anatomy and Physiology of the Small Bowel.

PubMed

Volk, Neil; Lacy, Brian

2017-01-01

Comprehension of small intestine physiology and function provides a framework for the understanding of several important disease pathways of the gastrointestinal system. This article reviews the development, anatomy and histology of the small bowel in addition to physiology and digestion of key nutrients. Copyright © 2016 Elsevier Inc. All rights reserved.

Distribution and Characterisation of Goblet Cells in the Large Intestine of Ostriches during the Pre- and Post-Hatch Period.

PubMed

Duritis, I; Mugurevics, A

2016-12-01

The role of goblet cell secretion, containing mucopolysaccharides, in the formation of a protective barrier of intestinal mucosa and transportation of the intestinal content has been described quite extensively. However, information on the quality composition of mucopolysaccharides and its changes in the intestinal tract of ostrich chicks, especially in the large intestinal segments, is unavailable. In the current study, ostrich embryos/chicks (n = 6/36) of both sexes were used shortly before hatching and during the first months of the post-hatch period. Tissues for histology were taken from the large intestine: the medium segments of the caecum, proximal and distal parts of colon. By using histochemical reactions, the differentiation of goblet cells as well as chemical composition of mucopolysaccharides was carried out. The cells contained acid (AB+), neutral (PAS+) and mixed (AB/PAS+) mucopolysaccharides. The number of goblet cells in the large intestine per unit area of mucosa increased towards the cloaca, and it was the highest in the distal part of the colon. The qualitative goblet cell composition in different large intestinal parts was different in all ages. In the caecum, goblet cells containing acid and mixed mucopolysaccharides dominate post-hatch, whereas in the colon, goblet cells containing acid mucopolysaccharides predominated. The most rapid changes in the qualitative goblet cell composition occur during the first week post-hatch when in all the intestinal segments the proportion of cells containing acid mucopolysaccharides continuously increased. © 2015 Blackwell Verlag GmbH.

The Turning Point for Morphomechanical Remodeling During Complete Intestinal Obstruction in Rats Occurs After 12-24 h.

PubMed

Sun, Daming; Zhao, Jingbo; Liao, Donghua; Huang, Zhiyong; Gregersen, Hans

2018-05-01

Intestinal obstruction prompts luminal dilation and wall remodeling proximal to the site of obstruction. Studies on temporal and spatial morphomechanical remodeling are needed for comprehending the pathophysiology of acute intestinal obstruction. The aim was to estimate the no-load and zero-stress morphomechanical properties in circumferential and longitudinal direction at 0, 6, 12, 24, 36, and 48 h after complete intestinal obstruction. Obstruction of the distal ileum was created surgically by placement of a polyethylene ring for up to 48 h in 30 rats. Sham and normal groups were also studied (n = 12). Five 6 cm-long intestinal segments proximal to the obstruction site were used for histological, morphometric and mechanical analysis at the designated times. Morphomechanical changes were huge but only subtle changes were observed between the 5 segments during the obstruction period. Due to dilation, the serosal length and mucosal length increased continuously from 6 to 48 h (p < 0.001). The wall area increased at 24 h and beyond (p < 0.001), demonstrating tissue growth. The opening and bending angle decreased to minimum values at 24 h where after the opening angle increased and the bending angle returned to pre-obstruction levels. For the residual stretch ratios and the position of the neutral axis the turning point was found after 24 h. Histologically, the thickness and area of most wall layers were quite stable for the first 12 h but with an increase at the 24 h time point that continued to the 48 h time point. The most pronounced change was found for the circumferential muscle layer (p < 0.05). Analysis of picrosirius red stained slides showed that submucosal type 3 collagen fraction increased significantly (p < 0.001), whereas the fraction of type 1 collagen decreased (p < 0.001). In conclusion, pronounced time-dependent morphomechanical remodeling was found. The obstructed intestine went from dilation remodeling to growth remodeling during the interval 12-24 h after creating the obstruction.

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

PubMed Central

de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

2017-01-01

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model.

PubMed

Hussein, Mahmoud R; Abu-Dief, Eman E; Kamel, Esam; Abou El-Ghait, Amal T; Abdulwahed, Saad Rezk; Ahmad, Mohamed H

2008-11-01

Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis". We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved. Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.

Observations on associated histopathology with Aggregata octopiana infection (Protista: Apicomplexa) in Octopus vulgaris.

PubMed

Gestal, C; Abollo, E; Pascual, S

2002-06-21

Gamogony and sporogony of Aggregata octopiana were commonly observed during histological examination of the digestive tract of wild Octopus vulgaris from Ria de Vigo (NW Spain). A. octopiana infected noncuticularized caecum and intestine, and cuticularized oesophagus and crop. Infection was also observed in the gills and in covering mesenterium, mainly of the digestive gland and gonad. Histological and ultrastructural lesions associated with A. octopiana included host cell hypertrophy with nuclear displacement, inflammation, phagocytosis, ulceration and destruction of organ architecture. The possible existence of a malabsorption syndrome in the host is deduced.

[Histological diagnosis and complications of celiac disease. Update according to the new S2k guidelines].

PubMed

Aust, D E; Bläker, H

2015-03-01

Celiac disease is a relatively common immunological systemic disease triggered by the protein gluten in genetically predisposed individuals. Classical symptoms like chronic diarrhea, steatorrhea, weight loss and growth retardation are nowadays relatively uncommon. Diagnostic workup includes serological tests for IgA antibodies against tissue transglutaminase 2 (anti-TG2-IgA) and total IgA and histology of duodenal biopsies. Histomorphological classification should be done according to the modified Marsh-Oberhuber classification. Diagnosis of celiac disease should be based on serological, clinical, and histological findings. The only treatment is a life-long gluten-free diet. Unchanged or recurrent symptoms under gluten-free diet may indicate refractory celiac disease. Enteropathy-associated T-cell lymphoma and adenocarcinomas of the small intestine are known complications of celiac disease.

Supplemental calcium attenuates the colitis-related increase in diarrhea, intestinal permeability, and extracellular matrix breakdown in HLA-B27 transgenic rats.

PubMed

Schepens, Marloes A A; Schonewille, Arjan J; Vink, Carolien; van Schothorst, Evert M; Kramer, Evelien; Hendriks, Thijs; Brummer, Robert-Jan; Keijer, Jaap; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2009-08-01

We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function may alleviate inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental calcium on spontaneous colitis development in an experimental rat model of IBD. HLA-B27 transgenic rats were fed a purified high-fat diet containing either a low or high calcium concentration (30 and 120 mmol CaHPO4/kg diet, respectively) for almost 7 wk. Inert chromium EDTA (CrEDTA) was added to the diets to quantify intestinal permeability by measuring urinary CrEDTA excretion. Relative fecal wet weight was determined to quantify diarrhea. Colonic inflammation was determined histologically and by measuring mucosal interleukin (IL)-1beta. In addition, colonic mucosal gene expression of individual rats was analyzed using whole-genome microarrays. The calcium diet significantly inhibited the increase in intestinal permeability and diarrhea with time in HLA-B27 rats developing colitis compared with the control transgenic rats. Mucosal IL-1beta levels were lower in calcium-fed rats and histological colitis scores tended to be lower (P = 0.08). Supplemental calcium prevented the colitis-induced increase in the expression of extracellular matrix remodeling genes (e.g. matrix metalloproteinases, procollagens, and fibronectin), which was confirmed by quantitative real-time PCR and gelatin zymography. In conclusion, dietary calcium ameliorates several important aspects of colitis severity in HLA-B27 transgenic rats. Reduction of mucosal irritation by luminal components might be part of the mechanism. These results show promise for supplemental calcium as effective adjunct therapy for IBD.

[Dolichomegacolon of the Andes and intestinal volvulus due to altitude].

PubMed

Frisancho, Oscar

2008-01-01

Sigmoid volvulus is a frequent cause of emergencies in hospitals in the Andean area, representing more than 50% of all intestinal obstructions. Andean dolichomegacolon (DCMA) and retractile mesocolonitis are the main contributing factors for volvulus. The mesocolonitis nears the proximal and distal segment of the sigmoid handle, favoring its torsion. Copious intake of fermentable food is the precipitating factor for volvulus. The majority of patients are seen during sowing and harvest periods, in which the consumption of this type of food increases. Andean people who live at an altitude of 3,000 m have a larger and thicker colon than coastal residents. We call this acquired characteristic the Andean dolichomegacolon (DCMA). A fiber-rich diet may inhibit the histological phenomenon known as elastogenesis, developing--over the years--the megacolon. Another important factor may be the lower atmospheric pressure in the altitude, and according to Boyle and Mariotte's physical law, the expansion of intraluminal gas may have an influence on intestinal enlargement. DCMA has many special anatomic, clinical, radiological, histological and serological features which make it different from the . chagasic megacolon. Mild emergency procedures may be performed to treat the sigmoid volvulus, such as endoscopic disvolvulation. Changing the colon rotation is helpful in diminishing abdominal pressure and restore complete blood circulation. An emergency surgery treatment must take the patient's general condition and the colon handle condition during surgery as a guiding point. High rates of mortality are found in relation to elderly patients, disease evolution time and stage of intestinal ischemia. Other new therapeutic procedures such as percutaneous sigmoidpexy, laparoscopic sigmoidectomy and mesosigmoplasty are under review, and have precise indications. Wider series are needed to evaluate them better.

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

PubMed Central

Seiler, Kristen M; Schenhals, Erica L; von Furstenberg, Richard J; Allena, Bhavya K; Smith, Brian J; Scaria, Denny; Bresler, Michele N; Dekaney, Christopher M; Henning, Susan J

2015-01-01

The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR) and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR. At this time point, flow cytometry on tissue collected 1 hour after EdU administration revealed increased numbers of CD24loUEA− ISCs and increased percentage of ISCs cycling. In culture, crypts harvested from DXR-treated mice were equally proliferative as those of control mice. Addition of subepithelial intestinal tissue (SET) collected 4 days after DXR elicited increased budding (1.4 ± 0.3 vs. 5.1 ± 1.0 buds per enteroid). Microarray analysis of SET collected 4 days after DXR revealed 1,030 differentially expressed transcripts. Cross comparison of Gene Ontology terms considered relevant to ISC activation pointed to 10 candidate genes. Of these the epidermal growth factor (EGF) family member amphiregulin and the BMP antagonist chordin-like 2 were chosen for further study. In crypt culture, amphiregulin alone did not elicit significant budding, but amphiregulin in combination with BMP antagonism showed marked synergism (yielding 6.3 ± 0.5 buds per enteroid). These data suggest a critical role for underlying tissue in regulating ISC behavior after damage, and point to synergism between amphiregulin and chordin-like 2 as factors which may account for activation of ISCs in the regenerative phase. PMID:25693894

Expression of the Na+/l- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

PubMed Central

Altorjay, Áron; Dohán, Orsolya; Szilágyi, Anna; Paroder, Monika; Wapnir, Irene L; Carrasco, Nancy

2007-01-01

Background The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease. PMID:17214887

Dietary betaine accumulates in the liver and intestinal tissue and stabilizes the intestinal epithelial structure in healthy and coccidia-infected broiler chicks.

PubMed

Kettunen, H; Tiihonen, K; Peuranen, S; Saarinen, M T; Remus, J C

2001-11-01

The aim of this experiment was to study the patterns of betaine accumulation into intestinal tissue, liver and plasma of broiler chicks with or without coccidial infection. The chicks were raised on a corn-based, low-betaine diet with or without 1000 ppm betaine supplementation and with or without intestinal microparasite (Eimeria maxima) challenge to the age of 21 days. Plasma, liver, intestinal tissue and digesta of non-challenged (NC) birds and plasma and intestinal tissue of coccidiosis challenged (CC) birds were analysed for betaine content. NC birds were also analyzed for homocysteine in plasma and S-adenosylmethionine (S-AM) in liver. The jejunal epithelium was histologically examined for the presence of coccidia and the crypt-villus ratio was measured. Dietary betaine supplementation decreased the plasma homocysteine concentration but had no effect on liver S-AM of NC birds. The data suggest that chicks on a low-betaine diet accumulate betaine into the intestinal tissue. When the diet was supplemented with betaine, betaine accumulated heavily into liver and to a lesser degree into intestinal tissue. The concentration of betaine in jejunal and ileal digesta was low suggesting that dietary betaine was mainly absorbed from the proximal small intestine. The coccidial challenge decreased the concentration of betaine in the liver, but greatly increased that in the intestinal tissue. The crypt-villus ratio was decreased by the dietary betaine supplementation in healthy and challenged chicks, suggesting that dietary betaine both protects the jejunal villi against coccidial infection and also stabilizes the mucosal structure in healthy broiler chicks. These results support our earlier findings suggesting that betaine is likely to act as an important intestinal osmolyte in broiler chicks.

The Small Intestine in Experimental Acute Iron Poisoning

PubMed Central

Hosking, C. S.

1971-01-01

A histological examination of the small intestine of rats following acute iron poisoning by ingestion of ferrous sulphate solution is presented. The changes that occur depend on the dose and can be broadly divided into 2 classes. When a very large dose is given (greater than 0·3 mg. Fe/g.), there is gross shrinkage of the villi, sub-epithelial oedema and eventual loss of epithelium. With doses less than 0·2 mg. Fe/g., contraction of villi was not so obvious, but as the animals survive longer with the lower dose, the changes often progressed to gross destruction of the villous stalk. Some of the animals given smaller doses survived and in those that were killed after 24 hr, the mucosa of the small intestine was essentially normal. ImagesFigs. 1-4Figs. 5-7Figs. 8-11 PMID:5547659

Primary mucinous adenocarcinoma of the vulva, intestinal type

PubMed Central

Lee, In Ho; Kim, Mi Kyung; Lee, Yoo Kyung; Hong, Sung Ran

2017-01-01

Primary vulva malignancy is a rare gynecologic malignancy. Most of them are squamous cell carcinomas and adenocarcinomas are much less common. Intestinal type is a rare variant of primary adenocarcinoma of the vulva. It histologically resembles mucinous colonic carcinomas. Origin from cloacal remnants has been suggested but remains speculative. A 64-year-old woman was referred to our clinic with a 1-month history of an itching vulva mass. An incisional biopsy was performed at other hospital and disclosed adenocarcinoma of intestinal type. Extensive workups were performed to detect other underlying carcinomas but revealed nothing abnormal. She underwent wide local excision without lymph node dissection for a primary vulva carcinoma. She received no adjuvant therapy and has been free from recurrent disease for 12 months after surgery. The authors report a rare case and review the relevant literature. PMID:28791269

Effect of supplementation of prebiotic mannan-oligosaccharides and probiotic mixture on growth performance of broilers subjected to chronic heat stress

USDA-ARS?s Scientific Manuscript database

The present study was aimed at elucidating the effects of supplementing mannan-oligosaccharides (MOS) and probiotic mixture (PM) on growth performance, intestinal histology, and corticosterone concentrations in broilers kept under chronic heat stress (HS). Four hundred and fifty day-old chicks were...

Experimental infection with Cryptosporidium parvum IIaA21G1R1 subtype in immunosuppressed mice

USDA-ARS?s Scientific Manuscript database

Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection....

Re-evaluation of endogenous development of Eimeria bareillyi Gill, Chhabra and Lall, 1963 in water buffalo (Bubalus bubalis).

PubMed

Dubey, J P

2018-04-25

Water buffalo (Bubalus bubalis) is important for the economy of Asia, South America and parts of Europe. Coccidiosis is an important cause of neonatal mortality in livestock, including buffalo. Of more than 12 species of Eimeria in buffalo, Eimeria bareillyi is the most pathogenic. There are uncertainties concerning its asexual and sexual development. During a previously reported outbreak of fatal enteritis associated with E. bareillyi in buffaloes in the Netherlands, sections of small intestine were re-evaluated histologically and by transmission electron microscopy (TEM) to seek details of endogenous development. Profuse asexual multiplication occurred in the jejunum and ileum. Light microscopic examination revealed that parasites divided in two (probably endodyogeny) or more organisms. There were two or more generations of morphologically different merozoites; some of these observations were confirmed by TEM. Details of gametogonic development, including oocyst wall formation are provided. Schizogonic and gametogonic development described in the present study can serve as a guide for differential diagnosis of Eimeria species in histological sections of intestines of buffaloes.

Immunohistochemical study of the digestive tract of Oligosarcus hepsetus

PubMed Central

Vieira-Lopes, Danielle A; Pinheiro, Nadja L; Sales, Armando; Ventura, Adriana; Araújo, Francisco G; Gomes, Iracema D; Nascimento, Aparecida A

2013-01-01

AIM: To describe the histology of the digestive tract and to investigate the occurrence of endocrine cells in Oligosarcus hepsetus (O. hepsetus). METHODS: The digestive tract (DT) of O. hepsetus was divided into esophagus, two stomach regions (glandular and non-glandular) and two intestinal regions (anterior and posterior). These specimens were processed by routine histological techniques and stained with hematoxylin-eosin, Gomori’s trichrome, periodic acid Schiff (PAS) and Alcian blue (AB). An immunohistochemical method using avidin-biotin-peroxidase was employed. RESULTS: The esophagus is lined with a non-keratinized stratified squamous epithelium that is reactive to PAS and AB. The stomach has a mucosa lined with a simple columnar epithelium with mucus-secreting cells that are reactive only to PAS. The intestine has a simple columnar epithelium with a brush border and goblet cells that are reactive to PAS and AB. Somatostatin, serotonin and cholecystokinin immunoreactive cells were identified throughout the DT. CONCLUSION: This study revealed adaptations for the species’ diet and showed that the distribution and relative frequency of immunoreactive cells are similar to those of other fish. PMID:23569337

[Primary intestinal lymphangiectasia (Waldmann's disease)].

PubMed

Vignes, S; Bellanger, J

2017-08-31

Primary intestinal lymphangiectasia (PIL), Waldmann's disease, is a rare disorder of unknown etiology characterized by dilated intestinal lacteals leading to lymph leakage into the small-bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. The main symptom is bilateral lower limb edema. Edema may be moderate to severe including pleural effusion, pericarditis or ascites. Protein-losing enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance and diagnosis by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of biopsies. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Several B-cell lymphomas of the gastrointestinal tract or with extra-intestinal localizations were reported in PIL patients. A long-term strictly low-fat diet associated with medium-chain triglyceride and liposoluble vitamin supplementation is the cornerstone of PIL medical management. Octreotide, a somatostatin analog, have been proposed with an inconsistent efficacy in association with diet. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. A prolonged clinical and biological follow-up is recommended. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Evaluation of differentially expressed immune-related genes in intestine of Pelodiscus sinensis after intragastric challenge with lipopolysaccharide based on transcriptome analysis.

PubMed

Xu, Jiehao; Zhao, Jing; Li, Yiqun; Zou, Yiyi; Lu, Binjie; Chen, Yuyin; Ma, Youzhi; Xu, Haisheng

2016-09-01

Pelodiscus sinensis is the most common turtle species that has been raised in East and Southeast Asia. However, there are still limited studies about the immune defense mechanisms in its small intestine until now. In the present research, histological analysis and transcriptome analysis was performed on the small intestine of P. sinensis after intragastric challenge with LPS to explore its mechanisms of immune responses to pathogens. The result showed the number of intraepithelial lymphocytes (IELs) and goblet cells (GCs) in its intestine increased significantly at 48 h post-challenge with LPS by intragastrical route, indicating clearly the intestinal immune response was induced. Compared with the control, a total of 748 differentially expressed genes (DEGs) were identified, including 361 up-regulated genes and 387 down-regulated genes. Based on the Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG), 48 immune-related DEGs were identified, which were classified into 82 GO terms and 14 pathways. Finally, 18 DEGs, which were randomly selected, were confirmed by quantitative real-time PCR (qRT-PCR). Our results provide valuable information for further analysis of the immune defense mechanisms against pathogens in the small intestine of P. sinensis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of cyclooxygenase-2 in intestinal injury in neonatal rats.

PubMed

Lu, Hui; Zhu, Bing

2014-11-01

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC remains poorly understood. The present study aimed to investigate the dynamic change and role of cyclooxygenase-2 (COX-2) in neonatal rats with intestinal injury. Wistar rats, <24 h in age, received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileal tissues were collected at 1, 3, 6, 12 and 24 h following the LPS challenge for histological evaluation of NEC and for measurements of COX-2 mRNA. The correlation between the degree of intestinal injury and expression of COX-2 mRNA was determined. The LPS-injected pups showed a significant increase in injury scores compared to the control, and the most deteriorating change was at 12 h. COX-2 mRNA expression was upregulated following LPS injection. There was a significantly positive correlation between COX-2 mRNA and the grade of intestinal injury within 12 h, whereas COX-2 mRNA expression had a significantly negative correlation with the severity of intestinal injury at 24 h. COX-2 plays an important role in LPS-induced intestinal injury and the repair processes. Caution should be exerted concerning the potential therapeutic uses of COX-2 inhibitors or promoters in NEC.

Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.

PubMed

Kadivar, Khadijeh; Ruchelli, Eduardo D; Markowitz, Jonathan E; Defelice, Magee L; Strogatz, Melissa L; Kanzaria, Mitul M; Reddy, Krishna P; Baldassano, Robert N; von Allmen, Daniel; Brown, Kurt A

2004-09-01

Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL-13 production. We evaluate IL-13, IL-6, and IL-1beta elaborations from colonic organ cultures of pediatric IBD patients Endoscopic lamina propria biopsies or surgical specimens from pediatric patients with IBD were organ cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL-1beta, IL-6, and IL-13. IL-13 concentrations were significantly reduced in ulcerative colitis (UC) patients when compared with normal controls (P = 0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at colectomy had lower intestinal IL-13 production than all other UC patients (P = 0.002). No significant correlation was found between IL-13 concentration and histologic disease severity (P = 0.134). Diminished intestinal IL-13 production is present in UC patients and wanes further with clinical disease progression. These findings suggest that UC patients may be differentiated from CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL-13 enhancing therapies. Copyright 2004 Lippincott Williams & Wilkins

A novel model for simultaneous study of neointestinal regeneration and intestinal adaptation.

PubMed

Jwo, Shyh-Chuan; Tang, Shye-Jye; Chen, Jim-Ray; Chiang, Kun-Chun; Huang, Ting-Shou; Chen, Huang-Yang

2013-01-01

The use of autologous grafts, fabricated from tissue-engineered neointestine, to enhance insufficient compensation of intestinal adaptation for severe short bowel syndrome is a compelling idea. Unfortunately, current approaches and knowledge for neointestinal regeneration, unlike intestinal adaptation, are still unsatisfactory. Thus, we have designed a novel model of intestinal adaptation with simultaneous neointestinal regeneration and evaluated its feasibility for future basic research and clinical application. Fifty male Sprague-Dawley rats weighing 250-350 g underwent this procedure and sacrificed at 4, 8, and 12 weeks postoperatively. Spatiotemporal analyses were carried out by gross, histology, and DNA/protein quantification. Three rats died of operative complications. In early experiments, the use of hard silicone stent as tissue scaffold in 11 rats was unsatisfactory for neointestinal regeneration. In later experiments, when a soft silastic tube was used, the success rate increased up to 90.9%. Further analyses revealed that no neointestine developed without donor intestine; regenerated lengths of mucosa and muscle were positively related to time postsurgery but independent of donor length with 0.5 or 1 cm. Other parameters of neointestinal regeneration or intestinal adaptation showed no relationship to both time postsurgery and donor length. In conclusion, this is a potentially important model for investigators searching for solutions to short bowel syndrome. © 2013 by the Wound Healing Society.

Benign intestinal glandular lesions in the vagina: a possible correlation with implantation.

PubMed

Lu, Weiwei; Zhang, Xiaofei; Lu, Bingjian

2016-06-17

Enteric-type glandular lesions are extremely rare in the vagina. Their histological origin remains a matter of speculation at present. We review two rectal mucosal prolapse-like polyps and one intestinal-type adenosis in the vagina. Case 1, a 64-year-old woman, presented with a vaginal polypoid lesion with a size of 4 × 3 × 3 cm. Case 2, an 8-year-old girl, had a 1.5 × 1.5 × 0.8-cm pedunculated polyp in the vaginal navicular fossa and a clinically suspected rectovaginal fistula. Case 1 and 3 had an obsolete severe perineal laceration. On histopathological examination, cases 1 and 2 resembled rectal mucosal prolapse or inflammatory cloacogenic polyp (rectal mucosal prolapse-like polyp). Case 3 had an incidental intestinal-type adenosis in the removed vaginal wall. Immunohistochemistry confirmed the intestinal differentiation in all 3 lesions by showing diffuse CDX2-positive, CK20-positive, and scattered chromogranin A-positive neuroendocrinal cells in the lower compartment of the crypt. In summary, we report herein three unusual cases of benign intestinal-type glandular lesions in the vagina including two rectal mucosal prolapse-like polyps and one case of intestinal-type adenosis, and discuss possibilities for their histogenetic basis.

Morphological, histological and molecular characterization of three Myxobolus species (Cnidaria: Myxosporea) from silver carp Hypophthalmichthys molitrix Valenciennes and bighead carp Hypophthalmichthys nobilis Richardson in China.

PubMed

Zhang, Bo; Gu, Zemao; Liu, Yang

2018-05-01

Three Myxobolus species were obtained from silver carp Hypophthalmichthys molitrix Valenciennes and bighead carp Hypophthalmichthys nobilis Richardson in China. In the present study, we supplemented their taxonomic characteristics by the morphological, histological and molecular methods. Myxobolus kiuchowensis Chen in Chen et Ma, 1998 formed small ellipsoidal plasmodia in the intestinal wall of bighead carp. Its spores appeared asymmetrical obovate in frontal view and fusiform in lateral view. Tiny mamillary protrusion in the anterior of some spores was observed. Two pyriform polar capsules were unequal. Histologically, M. kiuchowensis infected the tunica muscularis of host intestine. Myxobolus abitus Li et Nie, 1973 formed sausage-like plasmodia in the gills of silver carp. Its spores appeared oblate in frontal view and fusiform in lateral view. Two pyriform polar capsules were unequal and an obvious inter-capsule appendix was observed. Histological examination revealed that M. abitus developed in the interlamellar-epithelium of host gills. Myxobolus pavlovskii (Akhmerov, 1954) Landsberg et Lom, 1991 formed sausage-like plasmodia both in the gills of silver carp and bighead carp. Spores of M. pavlovskii were proximate oval in frontal view and fusiform in lateral view. Two pyriform polar capsules were unequal. The BLAST search indicated the SSU rDNA sequences of M. kiuchowensis and M. abitus were not identical to any sequence, however, the SSU rDNA sequences of M. pavlovskii were identical to that of M. pavlovskii recorded previously. Phylogenetic analysis showed that the present three species robustly clustered together in Cyprinid group and Asia group. Copyright © 2018. Published by Elsevier B.V.

Inflammatory Bowel Disease.

PubMed

2016-01-01

Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed.

Growth performance and histological intestinal alterations in piglets fed dietary raw and heated pigeon pea seed meal.

PubMed

Mekbungwan, A; Yamauchi, K

2004-04-01

Histological intestinal villus alterations were studied in piglets fed raw (PM) or heated (HPM) pigeon pea seed meal. The trypsin inhibition rate was 99.15% in PM and 54.31% HPM. The PM and HPM were added into the basal diet (crude protein; 176.3 g/kg, gross energy; 4.15 kcal/g, control) at 20% and 40% levels, respectively. The diets were formulated in order to adjust protein to 180 g/kg and gross energy to about 4.20 kcal/g. The feed intake was not different among groups. The daily body weight gain and feed efficiency tended to decrease with the increasing PM level, and they decreased significantly in the 40% PM group compared with the control group (P < 0.05). However, HPM groups showed a growth performance similar to the control. The villus height, cell area and cell mitosis tended to decrease with the increasing PM level, and they decreased significantly in the 40% PM group compared with the control group (P < 0.05). In HPM group, these villus height, cell area and cell mitosis were significantly higher than those of the 40% PM group (P < 0.05), and did not show a significant difference compared with the control. Compared with the duodenal villus surface of the control group, the PM groups had a smooth surface due to flat cells and the HPM group showed a rough surface due to protuberated cells. The current histological alterations of intestinal villi demonstrate that the villi might be atrophied in the piglets fed raw PM due to anti-nutritional factors, resulting in the decreased growth performance, and that heating PM might abolish such a harmful effect of the anti-nutritional factors on the villus function, resulting in a similar growth performance to the control. Raw PM could be incorporated under a level of 40%, but heated PM increases the incorporation rate up to the 40% level.

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

PubMed

Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

2015-11-02

Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

Synergistic Effects of Electroacupuncture and Mesenchymal Stem Cells on Intestinal Ischemia/Reperfusion Injury in Rats.

PubMed

Geng, Yanxia; Chen, Dong; Zhou, Jiang; Lu, Jun; Chen, Mingqi; Zhang, Haidong; Wang, Xing

2016-08-01

Electroacupuncture (EA) and transplantation of bone marrow mesenchymal stem cells (MSCs) are both promising therapeutic applications for intestinal disorders. The current study examined their combined effect on rat intestinal ischemia/reperfusion (I/R) injury and the possible mechanism. Five groups were performed: con group (shame operation),I/R group (model group), MSC group (I/R + MSC), EA group (I/R + EA), and combined group (I/R + MSC + EA). Intestinal histological damage, crypt cell proliferation degree, mucosal cytokines expression, and levels of inflammation factors were studied for each group. Compared with the I/R group, crypt cell proliferation index and mucosal mRNA concentration of SDF-1, CXCR4, EGF, EGFR in MSC group and EA group were significantly increased, with mucosal NF-кBp65 and serum inflammation factor (TNF-α, IL-6) levels significantly decreased. Above all of these indicators except NF-кBp65 were improved more notably in combined group than the other two treatment groups. Chiu's score was only ameliorated remarkably in the combined group. The combined treatment of MSC transplantion and electroacupuncture could protect intestinal mucosal barrier from I/R injury.

Molecular mechanism of dietary phospholipid requirement of Atlantic salmon, Salmo salar, fry.

PubMed

Carmona-Antoñanzas, G; Taylor, J F; Martinez-Rubio, L; Tocher, D R

2015-11-01

The phospholipid (PL) requirement in fish is revealed by enhanced performance when larvae are provided PL-enriched diets. To elucidate the molecular mechanism underlying PL requirement in Atlantic salmon, Salmo salar, were fed a minimal PL diet and tissue samples from major lipid metabolic sites were dissected from fry and parr. In silico analysis and cloning techniques demonstrated that salmon possess a full set of enzymes for the endogenous production of PL. The gene expression data indicated that major PL biosynthetic genes of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn) and phosphatidylinositol (PtdIns) display lower expression in intestine during the early developmental stage (fry). This is consistent with the hypothesis that the intestine of salmon is immature at the early developmental stage with limited capacity for endogenous PL biosynthesis. The results also indicate that intact PtdCho, PtdEtn and PtdIns are required in the diet at this stage. PtdCho and sphingomyelin constitute the predominant PL in chylomicrons, involved in the transport of dietary lipids from the intestine to the rest of the body. As sphingomyelin can be produced from PtdCho in intestine of fry, our findings suggest that supplementation of dietary PtdCho alone during early developmental stages of Atlantic salmon would be sufficient to promote chylomicron formation. This would support efficient transport of dietary lipids, including PL precursors, from the intestine to the liver where biosynthesis of PtdEtn, PtdSer, and PtdIns is not compromised as in intestine facilitating efficient utilisation of dietary energy and the endogenous production of membrane PL for the rapidly growing and developing animal. Copyright © 2015. Published by Elsevier B.V.

Gross morphology and histology of the alimentary tract of the convict cichlid Amatitlania nigrofasciata.

PubMed

Hopperdietzel, C; Hirschberg, R M; Hünigen, H; Wolter, J; Richardson, K; Plendl, J

2014-11-01

The primary objectives of this study were to document the macroscopic and histological structure of the alimentary tract (AT) of the convict cichlid Amatitlania nigrofasciata, because there are no data available for this omnivorous freshwater fish of the family Cichlidae. The morphology of the AT of A. nigrofasciata resembles that of related species. While having morphological criteria of the AT typical of most omnivorous fishes, such as a blind sac stomach and medium length intestine, A. nigrofasciata also has some structural peculiarities: the oesophagus is lined by a uniform stratified squamous epithelial layer with interspersed goblet cells along its entire length. Additionally, it has well-developed layers of the tunica muscularis including muscle fibre bundles that ascend into its mucosal folds. Occasionally, taste buds are present. In the transitional area between oesophagus and stomach, a prominent torus-like closure device is present. The mucosa of the stomach cannot be divided into different regions according to mucosal and morphological properties. The simple pattern of intestinal loops of A. nigrofasciata has few variations, irrespective of sex, mass and length of the individual fish. The first segment of the intestine is characterized by the largest mucososerosal ratio and the most complex mucosal surface architecture. A distinction of midgut and hindgut was not possible in A. nigrofasciata due to lack of defining structural components as described for other fish species. © 2014 The Fisheries Society of the British Isles.

Precision machining of pig intestine using ultrafast laser pulses

NASA Astrophysics Data System (ADS)

Beck, Rainer J.; Góra, Wojciech S.; Carter, Richard M.; Gunadi, Sonny; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

2015-07-01

Endoluminal surgery for the treatment of early stage colorectal cancer is typically based on electrocautery tools which imply restrictions on precision and the risk of harm through collateral thermal damage to the healthy tissue. As a potential alternative to mitigate these drawbacks we present laser machining of pig intestine by means of picosecond laser pulses. The high intensities of an ultrafast laser enable nonlinear absorption processes and a predominantly nonthermal ablation regime. Laser ablation results of square cavities with comparable thickness to early stage colorectal cancers are presented for a wavelength of 1030 nm using an industrial picosecond laser. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue. The depth of the ablation can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers to ablate pig intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

Beta-conglycinin and gut histology of sunshine bass fed diets with new varieties of non-GM soybeans

USDA-ARS?s Scientific Manuscript database

It is reported that the soybean protein (Beta-conglycinin) might cause inflammation of the distal intestine and stimulate endogenous cholecystokinin release that suppresses food intake in fish. We are studying the effects of meals made from new strains of non-GMO soybeans with high protein and redu...

Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).

PubMed

Qin, Chaobin; Yang, Liping; Zheng, Wenjia; Yan, Xiao; Lu, Ronghua; Xie, Dizhi; Nie, Guoxing

2018-01-08

The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

PubMed

Bell, T M; Bunton, T E; Shaia, C I; Raymond, J W; Honnold, S P; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

2016-01-01

Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development. © The Author(s) 2015.

Early intestinal growth and development in poultry.

PubMed

Lilburn, M S; Loeffler, S

2015-07-01

While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. © 2015 Poultry Science Association Inc.

The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

PubMed

Rötting, A K; Freeman, D E; Constable, P D; Moore, R M; Eurell, J C; Wallig, M A; Hubert, J D

2008-06-01

Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. P<0.05 was considered significant. There was no difference in large intestinal mucosal eosinophil counts and eosinophil distribution between ponies infected with S. vulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

Barrett's oesophagus: intestinal metaplasia is not essential for cancer risk.

PubMed

Kelty, Clive J; Gough, Martin D; Van Wyk, Quintin; Stephenson, Timothy J; Ackroyd, Roger

2007-11-01

Barrett's oesophagus is the main identifiable risk factor for oesophageal adenocarcinoma. It has been suggested that only patients with intestinal metaplasia are at risk of cancer, but the British Society of Gastroenterology (BSG) guidelines suggest that glandular mucosa is all that is needed. The aim of this study was to quantify the risk of adenocarcinoma in columnar-lined lower oesophagus, with or without specialized intestinal metaplasia. All patients who had endoscopic biopsies of the lower oesophagus between 1980 and 1994 in a single-centre teaching hospital were included in the study. All histological specimens were re-examined and reported according to whether they contained columnar epithelial-lined lower oesophagus, glandular mucosa, with or without intestinal metaplasia. The primary outcome measure was the development of adenocarcinoma. In total, 712 patients were identified. Of these, 379 (55.1%) were found to have specialized intestinal metaplasia (SIM), and the remaining 309 (44.9%, p = NS) were reported as having glandular mucosa (GM). The median follow-up for patients was 12 years (range 8-20 years). Twenty-eight patients went on to develop adenocarcinoma (4.1%) during the follow-up period - 17 in the SIM group (4.5%) and 11 in the GM group (3.6%, p =NS). The oesophageal malignancy rate was 0.34% per year (SIM 0.37%, GM 0.30%; p =NS). Patients who have glandular mucosa on biopsy without intestinal metaplasia have a similar cancer risk to those with specialized intestinal metaplasia.

Protective Effects of Thymoquinone and Melatonin on Intestinal Ischemia–reperfusion Injury

PubMed Central

Tas, Ufuk; Ayan, Murat; Sogut, Erkan; Kuloglu, Tuncay; Uysal, Murat; Tanriverdi, Halil I.; Senel, Ufuk; Ozyurt, Birsen; Sarsilmaz, Mustafa

2015-01-01

Background/Aim: In the present study, we aimed to compare the potential protective effects of thymoquinone and melatonin by using equivalent dose, on oxidative stress-induced ischemia–reperfusion (IR) injury in the intestinal tissue of rats. Materials and Methods: The study was performed using 32 male Wistar–Albino rats (weighing 180–200 g) randomly divided into four groups: Group I, sham group; Group II, IR group; Group III, IR with melatonin group; and Group IV, IR with thymoquinone group. After laparotomy, ischemia and reperfusion were performed for 60 and 120 min, respectively, on all the groups. Intestinal tissue sections were stained using routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using the TUNEL method for determination of apoptosis. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) levels in the intestinal tissue were also measured. Results: The IR group had significantly elevated tissue SOD activity, GSH-Px activity, and MDA levels compared with the sham group. Administration of thymoquinone and melatonin efficiently reduced these increases. Statistically significant number of apoptotic cells was observed in the intestinal tissue of IR group rats compared with the sham group. Treatment with thymoquinone and melatonin markedly reduced the number of apoptotic cells. Conclusion The effects of melatonin and thymoquinone on IR-induced oxidative stress in rat intestines were similar. Our findings suggest that melatonin and thymoquinone protect against IR-induced injury to intestinal tissues. PMID:26458854

Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

PubMed Central

Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung

2014-01-01

Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699

Avian Influenza Virus Subtype H9N2 Affects Intestinal Microbiota, Barrier Structure Injury, and Inflammatory Intestinal Disease in the Chicken Ileum.

PubMed

Li, Hongxin; Liu, Xiaolin; Chen, Feiyang; Zuo, Kejing; Wu, Che; Yan, Yiming; Chen, Weiguo; Lin, Wencheng; Xie, Qingmei

2018-05-18

Avian influenza virus subtype H9N2 (H9N2 AIV) has caused significant losses to the poultry industry due to the high mortality associated with secondary infections attributable to E. coli . This study tries to address the underlying secondary mechanisms after H9N2 AIV infection. Initially, nine day-old specific pathogen-free chickens were assigned to control (uninfected) and H9N2-infected groups, respectively. Using Illumina sequencing, histological examination, and quantitative real-time PCR, it was found that H9N2 AIV caused intestinal microbiota disorder, injury, and inflammatory damage to the intestinal mucosa. Notably, the genera Escherichia , especially E. coli , significantly increased ( p < 0.01) at five days post-infection (dpi), while Lactobacillus , Enterococcus , and other probiotic organisms were significantly reduced ( p < 0.01). Simultaneously, the mRNA expression of tight junction proteins ( ZO-1 , claudin 3, and occludin), TFF2, and Muc2 were significantly reduced ( p < 0.01), indicating the destruction of the intestinal epithelial cell tight junctions and the damage of mucin layer construction. Moreover, the mRNA expression of proinflammatory cytokines IFN-γ, IL-22, IFN-α, and IL-17A in intestinal epithelial cells were significantly upregulated, resulting in the inflammatory response and intestinal injury. Our findings may provide a theoretical basis for observed gastroenteritis-like symptoms such as diarrhea and secondary E. coli infection following H9N2 AIV infection.

Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy.

PubMed

Mizutani, T; Akiho, H; Khan, W I; Murao, H; Ogino, H; Kanayama, K; Nakamura, K; Takayanagi, R

2010-02-01

Inflammatory bowel disease (IBD) patients in remission often experience irritable bowel syndrome (IBS)-like symptoms. We investigated the mechanism for intestinal muscle hypercontractility seen in T-cell-induced enteropathy in recovery phase. BALB/c mice were treated with an anti-CD3 antibody (100 microg per mouse) and euthanized at varying days post-treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF-alpha) and serotonin (5-HT)-expressing enterochromaffin cell numbers in the small intestine. The role of 5-HT in anti-CD3 antibody-induced intestinal muscle function in recovery phase was assessed by inhibiting 5-HT synthesis using 4-chloro-DL-phenylalanine (PCPA). Small intestinal tissue damage was observed from 24 h after the anti-CD3 antibody injection, but had resolved by day 5. Carbachol-induced smooth muscle cell contractility was significantly increased from 4 h after injection, and this muscle hypercontractility was evident in recovery phase (at day 7). Th2 cytokines (IL-4, IL-13) were significantly increased from 4 h to day 7. 5-HT-expressing cells in the intestine were increased from day 1 to day 7. The 5-HT synthesis inhibitor PCPA decreased the anti-CD3 antibody-induced muscle hypercontractility in recovery phase. Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5-HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase.

High-Throughput Sequencing Identifies MicroRNAs from Posterior Intestine of Loach (Misgurnus anguillicaudatus) and Their Response to Intestinal Air-Breathing Inhibition.

PubMed

Huang, Songqian; Cao, Xiaojuan; Tian, Xianchang; Wang, Weimin

2016-01-01

MicroRNAs (miRNAs) exert important roles in animal growth, immunity, and development, and regulate gene expression at the post-transcriptional level. Knowledges about the diversities of miRNAs and their roles in accessory air-breathing organs (ABOs) of fish remain unknown. In this work, we used high-throughput sequencing to identify known and novel miRNAs from the posterior intestine, an important ABO, in loach (Misgurnus anguillicaudatus) under normal and intestinal air-breathing inhibited conditions. A total of 204 known and 84 novel miRNAs were identified, while 47 miRNAs were differentially expressed between the two small RNA libraries (i.e. between the normal and intestinal air-breathing inhibited group). Potential miRNA target genes were predicted by combining our transcriptome data of the posterior intestine of the loach under the same conditions, and then annotated using COG, GO, KEGG, Swissprot and Nr databases. The regulatory networks of miRNAs and their target genes were analyzed. The abundances of nine known miRNAs were validated by qRT-PCR. The relative expression profiles of six known miRNAs and their eight corresponding target genes, and two novel potential miRNAs were also detected. Histological characteristics of the posterior intestines in both normal and air-breathing inhibited group were further analyzed. This study contributes to our understanding on the functions and molecular regulatory mechanisms of miRNAs in accessory air-breathing organs of fish.

Parenteral Nutrition-Associated Liver Disease: The Role of the Gut Microbiota.

PubMed

Cahova, Monika; Bratova, Miriam; Wohl, Petr

2017-09-07

Parenteral nutrition (PN) provides life-saving nutritional support in situations where caloric supply via the enteral route cannot cover the necessary needs of the organism. However, it does have serious adverse effects, including parenteral nutrition-associated liver disease (PNALD). The development of liver injury associated with PN is multifactorial, including non-specific intestine inflammation, compromised intestinal permeability, and barrier function associated with increased bacterial translocation, primary and secondary cholangitis, cholelithiasis, short bowel syndrome, disturbance of hepatobiliary circulation, lack of enteral nutrition, shortage of some nutrients (proteins, essential fatty acids, choline, glycine, taurine, carnitine, etc.), and toxicity of components within the nutrition mixture itself (glucose, phytosterols, manganese, aluminium, etc.). Recently, an increasing number of studies have provided evidence that some of these factors are directly or indirectly associated with microbial dysbiosis in the intestine. In this review, we focus on PN-induced changes in the taxonomic and functional composition of the microbiome. We also discuss immune cell and microbial crosstalk during parenteral nutrition, and the implications for the onset and progression of PNALD. Finally, we provide an overview of recent advances in the therapeutic utilisation of pro- and prebiotics for the mitigation of PN-associated liver complications.

Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.

PubMed

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-10-27

Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

[Primary intestinal lymphangiectasia: twenty years of experience at a Mexican tertiary care hospital].

PubMed

Valdovinos-Oregón, D; Ramírez-Mayans, J; Cervantes-Bustamante, R; Toro-Monjaraz, E; Cázares-Méndez, M; Cadena-León, J; Zárate-Mondragón, F; Montijo-Barrios, E

2014-01-01

Primary intestinal lymphangiectasia is a rare congenital disease described by Waldmann in 1961 that is a consequence of obstruction of the lymphatic drainage of the small bowel with secondary lymph vessel dilation. This distorts the architecture of the villi and causes a leakage of lymph into the intestinal lumen, resulting in protein-losing enteropathy and malabsorption. To describe the clinical, biochemical, radiologic, endoscopic, and histologic characteristics in children with primary intestinal lymphangiectasia. A retrospective observational, descriptive, cross-sectional study was conducted that reviewed the case records of children diagnosed with primary intestinal lymphangiectasia that were seen at the Department of Gastroenterology and Nutrition of the Instituto Nacional de Pediatría within the time frame of January 1, 1992 to September 30, 2012. Four patients were found that presented with primary intestinal lymphangiectasia. Three of them had been diagnosed before 3 years of age. All the patients presented with chronic diarrhea, edema, lymphopenia, hypocalcemia, and hypogammaglobulinemia, and 3 patients presented with hypocholesterolemia. Bowel transit time, endoscopy, and intestinal biopsies were characteristic of this pathology. Intestinal lymphangiectasia should be suspected when there is a clinical picture of chronic diarrhea and protein-losing enteropathy accompanied with edema at any level, as well as hypoalbuminemia, hypocalcemia, lymphopenia, hypogammaglobulinemia, and hypocholesterolemia, which are the main biochemical findings of this pathology. All children presenting with intestinal lymphangiectasia should undergo an upper gastrointestinal series with bowel transit time and endoscopy with biopsies taken at the level of the duodenum. Treatment includes diet and the periodic administration of albumin and gamma globulin. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells.

PubMed

Jung, Kwang Bo; Lee, Hana; Son, Ye Seul; Lee, Ji Hye; Cho, Hyun-Soo; Lee, Mi-Ok; Oh, Jung-Hwa; Lee, Jaemin; Kim, Seokho; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

2018-01-01

Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters Krüppel-like factor 5 monomeric Cherry (KLF5 mCherry ) and intestine-specific homeobox enhanced green fluorescence protein (ISX eGFP ). Then hIOs were efficiently induced from those transgenic hiPSC lines in which mCherry- or eGFP-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.-Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells. © FASEB.

Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

PubMed Central

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-01-01

Background Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. Methods The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Results Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. Conclusion We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT. PMID:25321166

Intestinal morphology of the wild Atlantic salmon (Salmo salar).

PubMed

Løkka, Guro; Austbø, Lars; Falk, Knut; Bjerkås, Inge; Koppang, Erling Olaf

2013-08-01

The worldwide-industrialized production of Atlantic salmon (Salmo salar) has increased dramatically during the last decades, followed by diseases related to the on-going domestication process as a growing concern. Even though the gastrointestinal tract seems to be a target for different disorders in farmed fish, a description of the normal intestinal status in healthy, wild salmon is warranted. Here, we provide such information in addition to suggesting a referable anatomical standardization for the intestine. In this study, two groups of wild Atlantic salmon were investigated, consisting of post smolts on feed caught in the sea and of sexually mature, starved individuals sampled from a river. The two groups represent different stages in the anadromous salmon life cycle, which also are part of the production cycle of farmed salmon. Selected regions of gastrointestinal tract were subjected to morphological investigations including immunohistochemical, scanning electron microscopic, and morphometric analyses. A morphology-based nomenclature was established, defining the cardiac part of the stomach and five different regions of the Atlantic salmon intestine, including pyloric caeca, first segment of the mid-intestine with pyloric caeca, first segment of the mid-intestine posterior to pyloric caeca, second segment of the mid-intestine and posterior intestinal segment. In each of the above described regions, for both groups of fish, morphometrical measurements and regional histological investigations were performed with regards to magnitude and direction of mucosal folding as well as the composition of the intestinal wall. Additionally, immunohistochemistry showing cells positive for cytokeratins, α-actin and proliferating cell nuclear antigen, in addition to alkaline phosphatase reactivity in the segments is presented. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Effects of a charcoal powder-wood vinegar compound solution in piglets for raw pigeon pea seed meal.

PubMed

Mekbungwan, A; Yamauchi, K; Sakaida, T; Buwjoom, T

2008-03-01

Histological intestinal villus alterations were studied in piglets fed a raw pigeon pea meal (PM) diet including a powder mixture of amorphous charcoal carbon and wood vinegar compound solution (CWVC). Twenty-eight male castrated piglets were divided into seven dietary groups of four piglets each. The control group was fed raw PM supplemented to the basal diet (178 g/kg crude protein, 4.23 kcal/g gross energy) at 0 g/kg (CONT), 200 g/kg (PM200) and 400 g/kg (PM400). The treatment groups were fed CWVC in both PM200 and PM400 diet groups at levels of 10 g/kg and 30 g/kg (PM200 + CWVC10, PM200 + CWVC30, PM400 + CWVC10 and PM400 + CWVC30). With increasing dietary PM levels, daily feed intake tended to increase. In contrast, daily body-weight gain tended to decrease, significantly in the PM400 group (P < 0.05), resulting in a significant decrease of feed efficiency in PM groups (P < 0.05). Body-weight gain and feed efficiency were higher in the CWVC groups compared with the PM groups. The duodenum and ileum were longer (P < 0.05) in the PM400 group than in CONT, but were similar to CONT in CWVC groups. The liver was heavier (P < 0.05), whereas the weights of the heart, kidney and stomach were decreased in the CWVC groups than in other groups. Most values for the intestinal villus height, cell area and cell mitosis number were lower in PM groups than those in CONT (P < 0.05) for each intestinal segment; however, these values were higher in CWVC groups than in PM groups (P < 0.05). The epithelial cells on the duodenal villus surface of the PM200 group showed cell morphology almost similar to CONT. However, the PM400 group had a smooth villus surface due to the presence of flat cells. The epithelial cells of the CWVC groups were protuberated, resulting in a much rougher surface than CONT. The current growth performance and histological intestinal alterations in piglets fed PM and PM + CWVC diets demonstrate that the intestinal features might be atrophied by feeding PM, resulting in decreased growth performance. CWVC might prevent the harmful effects of PM dietary toxins on intestinal function, resulting in a normal growth performance.

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer

PubMed Central

Adam, Jason D.; Borum, Marie L.; Koh, Joyce M.; Stephen, Sindu

2018-01-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation. PMID:29606921

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer.

PubMed

Jencks, David S; Adam, Jason D; Borum, Marie L; Koh, Joyce M; Stephen, Sindu; Doman, David B

2018-02-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation.

CYP3A4-catalyzed simvastatin metabolism as a non-invasive marker of small intestinal health in celiac disease.

PubMed

Morón, Belén; Verma, Anil K; Das, Prasenjit; Taavela, Juha; Dafik, Laila; Diraimondo, Thomas R; Albertelli, Megan A; Kraemer, Thomas; Mäki, Markku; Khosla, Chaitan; Rogler, Gerhard; Makharia, Govind K

2013-08-01

Histological examination of duodenal biopsies is the gold standard for assessing intestinal damage in celiac disease (CD). A noninvasive marker of disease status is necessary, because obtaining duodenal biopsies is invasive and not suitable for routine monitoring of CD patients. As the small intestine is a major site of cytochrome P450 3A4 (CYP3A4) activity and also the location of the celiac lesion, we investigated whether patients with active CD display abnormal pharmacokinetics of an orally administered CYP3A4 substrate, simvastatin (SV), which could potentially be used for noninvasive assessment of their small intestinal health. Preclinical experiments were performed in CYP3A4-humanized mice to examine the feasibility of the test. Subsequently, a clinical trial was undertaken with 11 healthy volunteers, 18 newly diagnosed patients with CD, and 25 celiac patients who had followed a gluten-free diet (GFD) for more than 1 year. The maximum concentration (Cmax) of orally administered SV plus its major non-CYP3A4-derived metabolite SV acid (SV equivalent (SVeq)) was measured, and compared with clinical, histological, and serological parameters. In CYP3A4-humanized mice, a marked decrease in SV metabolism was observed in response to enteropathy. In the clinical setting, untreated celiac patients displayed a significantly higher SVeq Cmax (46±24 nM) compared with treated patients (21±16 nM, P<0.001) or healthy subjects (19±11 nM, P<0.005). SVeq Cmax correctly predicted the diagnosis in 16/18 untreated celiac patients, and also the recovery status of all follow-up patients that exhibited normal or near-normal biopsies (Marsh 0-2). All patients with abnormal SVeq Cmax showed a reduction in the value after 1 year of following a GFD. SVeq Cmax is a promising noninvasive marker for assessment of small intestinal health. Further studies are warranted to establish its clinical utility for assessing gut status of patients with CD.

Effect of the combination of fibrin glue and growth hormone on intestinal anastomoses in a pig model of traumatic shock associated with peritonitis.

PubMed

Wang, Pengfei; Wang, Jian; Zhang, Wenbo; Li, Yousheng; Li, Jieshou

2009-03-01

Intra-abdominal sepsis and hemorrhagic shock have been found to impair the healing of intestinal anastomoses. The present study examined whether fibrin glue (FG) and recombinant human growth hormone (GH) can improve intestinal primary anastomotic healing in a pig model of traumatic shock associated with peritonitis. Further, the study was designed to investigate the probable mechanism of these agents. Female anesthetized pigs were divided into five groups. Group sham (n = 7), pigs without traumatic shock had small bowel resection anastomoses; group control (n = 14), pigs had bowel resection anastomoses 24 h after abdominal gunshot plus exsanguination/resuscitation; group FG (n = 14); group GH (n = 14); group FG/GH (n = 14), pigs received FG, recombinant GH, or both, respectively. Recombinant GH was given daily for 7 days. Blood samples were collected daily for measurement of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha levels. Investigations also included adhesion formation, anastomotic bursting pressure, tensile strength, hydroxyproline (HP) content, myeloperoxidase (MPO), tumor necrosis factor (NF)-kappaB activity, and histology analysis 10 days later. A second experiment (n = 20 subjects assigned to each of the five groups) was designed to study survival during the first 20 postoperative days. Traumatic shock associated with peritonitis led to significant decreases in intestinal anastomotic bursting pressures, tensile strengths, and tissue hydroxyproline content, along with severe adhesion formation, increases in MPO activity and NF-kappaB activity, and plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Both FG and recombinant GH treatment led to early significant increases in plasma levels of TNF-alpha and IL-6. At the same time, FG alone, unlike recombinant GH alone, led to significant increases in anastomotic bursting pressures, tensile strength, and tissue HP content, along with decreases in anastomotic MPO and NF-kappaB activity and later plasma levels of TNF-a and IL-6. The FG group also developed more marked neoangiogenesis and collagen deposition on histology analysis. However, FG and recombinant GH synergistically effected improved anastomotic healing, abolishing the infaust effects promoted by recombinant GH. Adhesion formation after intestinal anastomosis could not be lowered by FG alone or by the combination of FG and recombinant GH. Both FG alone and FG/GH, in contrast to GH alone and control treatment, significantly prolonged the survival time of experimental animals. We found that FG, but not recombinant GH, could lower the risk of anastomotic leakage, improve intestinal anastomotic healing, and prolong survival in a pig model of traumatic shock associated with peritonitis. Both FG and recombinant GH synergistically effected improved intestinal anastomotic healing. It was suggested that GH could be used locally to promote intestinal anastomotic healing in intra-abdominal peritonitis.

Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation.

PubMed

Vinderola, Gabriel; Perdigón, Gabriela; Duarte, Jairo; Farnworth, Edward; Matar, Chantal

2006-11-01

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta).

PubMed

Liu, David X; Gilbert, Margaret H; Wang, Xiaolei; Didier, Peter J; Veazey, Ronald S

2012-11-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report.

The effect of NovaSil dietary supplementation on the growth and health performance of Nile tilapia (Oreochromis niloticus) fed aflatoxin-B1 contaminated feed

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the ability of NovaSil (NS) clay to sorb and mitigate the toxic effects of aflatoxin B1 (AFB1) in Nile tilapia (Oreochromis niloticus). Growth performance, specific innate immunological function, intestinal microbial community, and histology were evaluate...

Spring-mediated distraction enterogenesis in-continuity.

PubMed

Huynh, Nhan; Rouch, Joshua D; Scott, Andrew; Chiang, Elvin; Wu, Benjamin M; Shekherdimian, Shant; Dunn, James C Y

2016-12-01

Distraction enterogenesis has been investigated as a novel treatment for patients with short bowel syndrome (SBS) but has been limited by loss of intestinal length during restoration and need for multiple bowel surgeries. The feasibility of in-continuity, spring-mediated intestinal lengthening has yet to be demonstrated. Juvenile mini-Yucatan pigs underwent in-continuity placement of polycaprolactone (PCL) degradable springs within jejunum. Methods used to anchor the spring ends to the intestine included full-thickness sutures and a high-friction surface spring. Spring constant (k) was 6-15N/m. Bowel was examined for length and presence of spring at 1 to 4weeks. Animals tolerated in-continuity lengthening without bowel obstruction for up to 29days. In-continuity jejunum with springs demonstrated intestinal lengthening by 1.47-fold ±0.11. Five springs had detached prematurely, and lengthening could not be assessed. Histologically, in-continuity jejunum showed significantly increased crypt depth and muscularis thickness in comparison to normal jejunum. Self-expanding endoluminal springs placed in continuity could lengthen intestine without obstruction in a porcine model. This is the first study showing safety and efficacy of a self-expanding endoluminal device for distraction enterogenesis. This is proof-of-concept that in-continuity spring lengthening is feasible and demonstrates its therapeutic potential in SBS. Level 3. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of graded inclusion of white lupin (Lupinus albus) meal on performance, nutrient digestibility and intestinal morphology of broiler chickens.

PubMed

Kaczmarek, S A; Hejdysz, M; Kubiś, M; Rutkowski, A

2016-06-01

The aim of this study was to investigate the effect of white lupin (Lupinus albus) meal (WLM) addition on the intestinal viscosity, bird performance, nutrient utilisation and villi morphology of growing broiler chicks. The experiment was conducted with 480 broiler chicks divided into 6 dietary treatments, including a maize-soybean meal control diet (CON) and 5 experimental diets containing 100, 150, 200, 250 and 300 g/kg WLM. During the period from d 0 to 35, birds fed on 200 or higher WLM/kg were characterised by lower body weight gain and feed intake than CON. The use of 150 g of WLM/kg increased feed conversion ratio (FCR) compared to CON treatment. Apparent metabolisable energy corrected to zero N balance (AMEN) and apparent ileal digestibility of dry matter, ether extract, crude protein and starch, linearly decreased as WLM increased from 0 to 300 g/kg. There was a quadratic effect of WLM dose on sialic acid excretion. A strong negative linear correlation was found between the excretion of sialic acid and AMEN. The viscosity of ileal digesta was linearly increased as WLM increased. The effect of WLM dose on ileum villus height (VH) was linear, while that on ileum villus area (VA) was quadratic. Both parameters decreased as WLM increased from 0 to 300 g/kg. In conclusion, the use of over 150 g/kg of WLM in broiler diets depressed performance results. However, depression of nutrient utilisation was only observed when 250 or 300 g/kg of WLM was used.

Coeliac disease: the histology report.

PubMed

Villanacci, Vincenzo; Ceppa, Paola; Tavani, Enrico; Vindigni, Carla; Volta, Umberto

2011-03-01

To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team". Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.

PubMed

Bozeman, Andrew P; Dassinger, Melvin S; Birusingh, Rhea J; Burford, Jeffrey M; Smith, Samuel D

2013-04-01

Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

Intestinal cytokines in children with pervasive developmental disorders.

PubMed

DeFelice, Magee L; Ruchelli, Eduardo D; Markowitz, Jonathan E; Strogatz, Melissa; Reddy, Krishna P; Kadivar, Khadijeh; Mulberg, Andrew E; Brown, Kurt A

2003-08-01

A relationship between autism and gastrointestinal (GI) immune dysregulation has been postulated based on incidence of GI complaints as well as macroscopically observed lymphonodular hyperplasia and microscopically determined enterocolitis in pediatric patients with autism. To evaluate GI immunity, we quantitatively assessed levels of proinflammatory cytokines, interleukin (IL)-6, IL-8, and IL-1beta, produced by intestinal biopsies of children with pervasive developmental disorders. Fifteen patients, six with pervasive developmental disorders and nine age-matched controls, presenting for diagnostic colonoscopy were enrolled. Endoscopic biopsies were organ cultured, supernatants were harvested, and IL-6, IL-8, and IL-1beta levels were quantified by ELISA. Tissue histology was evaluated by blinded pathologists. Concentrations of IL-6 from intestinal organ culture supernatants of patients with pervasive developmental disorders (median 318.5 pg/ml, interquartile range 282.0-393.0 pg/ml) when compared with controls (median 436.9 pg/ml, interquartile range 312.6-602.5 pg/ml) were not significantly different (p = 0.0987). Concentrations of IL-8 (median 84,000 pg/ml, interquartile range 16,000-143,000 pg/ml) when compared with controls (median 177,000 pg/ml, interquartile range 114,000-244,000 pg/ml) were not significantly different (p = 0.0707). Concentrations of IL-1beta (median 0.0 pg/ml, interquartile range 0.0-94.7 pg/ml) when compared with controls (median 0.0 pg/ml, interquartile range 0.0-60.2 pg/ml) were not significantly different (p = 0.8826). Tissue histology was nonpathological for all patients. We have demonstrated no significant difference in production of IL-6, IL-8, and IL-1beta between patients with pervasive developmental disorders and age-matched controls. In general, intestinal levels of IL-6 and IL-8 were lower in patients with pervasive developmental disorders than in age-matched controls. These data fail to support an association between autism and GI inflammation.

TLR9 agonist protects mice from radiation-induced gastrointestinal syndrome.

PubMed

Saha, Subhrajit; Bhanja, Payel; Liu, Laibin; Alfieri, Alan A; Yu, Dong; Kandimalla, Ekambar R; Agrawal, Sudhir; Guha, Chandan

2012-01-01

Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption of mucosal barrier, bacterial invasion, inflammation and sepsis. Intestinal macrophages could recognize invading bacterial DNA via TLR9 receptors and transmit regenerative signals to the neighboring crypt. We therefore investigated whether systemic administration of designer TLR9 agonist could ameliorate RIGS by activating TLR9. Male C57Bl6 mice were distributed in four experimental cohorts, whole body irradiation (WBI) (8.4-10.4 Gy), TLR9 agonist (1 mg/kg s.c.), 1 h pre- or post-WBI and TLR9 agonist+WBI+iMyd88 (pretreatment with inhibitory peptide against Myd88). Animals were observed for survival and intestine was harvested for histological analysis. BALB/c mice with CT26 colon tumors in abdominal wall were irradiated with 14 Gy single dose of whole abdominal irradiation (AIR) for tumor growth study. Mice receiving pre-WBI TLR9 agonist demonstrated improvement of survival after 10.4 Gy (p<0.03), 9.4 Gy (p<0.008) and 8.4 Gy (p<0.002) of WBI, compared to untreated or iMyd88-treated controls. Post-WBI TLR9 agonist mitigates up to 8.4 Gy WBI (p<0.01). Histological analysis and xylose absorption test demonstrated significant structural and functional restitution of the intestine in WBI+TLR9 agonist cohorts. Although, AIR reduced tumor growth, all animals died within 12 days from RIGS. TLR9 agonist improved the survival of mice beyond 28 days post-AIR (p<0.008) with significant reduction of tumor growth (p<0.0001). TLR9 agonist treatment could serve both as a prophylactic or mitigating agent against acute radiation syndrome and also as an adjuvant therapy to increase the therapeutic ratio of abdominal Radiation Therapy for Gastro Intestinal malignancies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lajmanovich, Rafael C., E-mail: lajmanovich@hotmail.com; Faculty of Biochemistry and Biological Sciences; Junges, Celina M.

The effects of commercial formulations of Bacillus thuringiensisvar.israelensis (Bti) on non-target organisms are still a matter of debate; in amphibians, the risks of Bti are little known. To evaluate the toxicity of a commercial liquid (aqueous suspension, AS) formulation of Bti (Introban{sup ®}) on Leptodactylus latrans tadpoles, including median lethal concentration (LC{sub 50}) and no-and lowest–observed-effect concentrations (NOEC and LOEC, respectively), as well as the possible effects of Bti on oxidative responses, erythrocytes genotoxicity, and histology of the intestines. In the laboratory, tadpoles were exposed to nominal concentrations of 0 (control), 2.5, 5, 10, 20 and 40 mg/L of formulatedmore » Bti-AS. Glutathione S-transferase (GST) and catalase (CAT) activities, as well as formation of erythrocyte nuclear abnormalities (ENAs), and histological effect were measured in tadpoles displaying survival rates >85%. L. latrans tadpoles were sensitive to exposure to Bti-AS, reaching 100% mortality after 48 h of exposure at the highest concentration. Bti-AS induced GST and CAT enzymes and genotoxicity (erythrocyte's nuclear abnormalities), and caused intestine's histopathology. Our results demonstrate that toxicity of Bti-AS is dose-dependent for L. latrans tadpoles and that sublethal exposure alters enzymes of oxidative stress, induces genotoxicity, and causes intestine damage. Further research is needed to evaluate the ecotoxicological risk of the massive use of Bti formulations on amphibian populations that commonly used suburban wastewater or urban waterbodies to reproduce and where this biopesticide is frequently applied. - Highlights: • An ecotoxicological evaluation of a Bti formulation on amphibian was conducted. • Toxicity of Bti-AS was dose-dependent for Leptodactylus latrans tadpoles. • Sublethal exposure altered the enzymes of oxidative stress (GST and CAT). • Bti-AS was genotoxic because increased MN frequencies (CO: 0.82–2.74‰). • Bti-AS caused the inflammatory infiltration in the lamina propria of intestine.« less

Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis.

PubMed

Tito, Raul Y; Cypers, Heleen; Joossens, Marie; Varkas, Gaëlle; Van Praet, Liesbet; Glorieus, Elien; Van den Bosch, Filip; De Vos, Martine; Raes, Jeroen; Elewaut, Dirk

2017-01-01

Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohn's disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA. Gene analysis by 16S ribosomal RNA amplicon sequencing was used to compare the microbial composition in ileal and colonic biopsy specimens from 27 patients with SpA (14 with microscopic bowel inflammation, 13 without) and 15 healthy control subjects (ileal samples from all 15 subjects and colonic samples from 6). Spearman's rank correlation tests were used to assess correlations of the microbial composition with disease activity measures. The intestinal inflammation status (histologically normal versus acute or chronic inflammation) was strongly associated with the mucosal microbiota profile of patients with SpA. In inflamed biopsy tissue, the detected bacterial community composition clustered separately from that in noninflamed biopsy tissue (P < 0.05 by permutational multivariate analysis of variance, using hierarchical clustering on Bray-Curtis distances). Interestingly, abundance of the genus Dialister was found to be positively correlated with the Ankylosing Spondylitis Disease Activity Score (Spearman's rho = 0.62, false discovery rate-corrected q < 0.01). This finding was further supported by the low frequency of Dialister observed in noninflamed ileal and colonic biopsy tissue from patients with SpA and healthy controls. These findings demonstrate a significant difference in the intestinal microbial composition in patients with SpA who have microscopic gut inflammation compared to those without microscopic gut inflammation. Moreover, Dialister may represent a potential microbial marker of disease activity in SpA. © 2016, American College of Rheumatology.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

PubMed Central

Martinel Lamas, Diego J.; Carabajal, Eliana; Prestifilippo, Juan P.; Rossi, Luis; Elverdin, Juan C.; Merani, Susana; Bergoc, Rosa M.; Rivera, Elena S.; Medina, Vanina A.

2013-01-01

Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy. PMID:23922686

Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

PubMed Central

Hansen, Svein; Vollset, Stein Emil; Derakhshan, Mohammad H; Fyfe, Valerie; Melby, Kjetil K; Aase, Steinar; Jellum, Egil; McColl, Kenneth E L

2007-01-01

Background Non‐cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim To compare cardia versus non‐cardia cancer with respect to the premorbid state of the stomach. Methods Nested case–control study. To each of 129 non‐cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti‐H pylori antibodies, pepsinogen I:II and gastrin. Results Non‐cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non‐cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori‐positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non‐cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non‐cardia cancer, and the other associated with non‐atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer. PMID:17317788

Toxicity of Bacillus thuringiensis var. israelensis in aqueous suspension on the South American common frog Leptodactylus latrans (Anura: Leptodactylidae) tadpoles.

PubMed

Lajmanovich, Rafael C; Junges, Celina M; Cabagna-Zenklusen, Mariana C; Attademo, Andrés M; Peltzer, Paola M; Maglianese, Mariana; Márquez, Vanina E; Beccaria, Alejandro J

2015-01-01

The effects of commercial formulations of Bacillus thuringiensisvar.israelensis (Bti) on non-target organisms are still a matter of debate; in amphibians, the risks of Bti are little known. To evaluate the toxicity of a commercial liquid (aqueous suspension, AS) formulation of Bti (Introban(®)) on Leptodactylus latrans tadpoles, including median lethal concentration (LC50) and no-and lowest-observed-effect concentrations (NOEC and LOEC, respectively), as well as the possible effects of Bti on oxidative responses, erythrocytes genotoxicity, and histology of the intestines. In the laboratory, tadpoles were exposed to nominal concentrations of 0 (control), 2.5, 5, 10, 20 and 40 mg/L of formulated Bti-AS. Glutathione S-transferase (GST) and catalase (CAT) activities, as well as formation of erythrocyte nuclear abnormalities (ENAs), and histological effect were measured in tadpoles displaying survival rates >85%. L. latrans tadpoles were sensitive to exposure to Bti-AS, reaching 100% mortality after 48 h of exposure at the highest concentration. Bti-AS induced GST and CAT enzymes and genotoxicity (erythrocyte's nuclear abnormalities), and caused intestine's histopathology. Our results demonstrate that toxicity of Bti-AS is dose-dependent for L. latrans tadpoles and that sublethal exposure alters enzymes of oxidative stress, induces genotoxicity, and causes intestine damage. Further research is needed to evaluate the ecotoxicological risk of the massive use of Bti formulations on amphibian populations that commonly used suburban wastewater or urban waterbodies to reproduce and where this biopesticide is frequently applied. Copyright © 2014 Elsevier Inc. All rights reserved.

Histology and immunohistochemistry of severe inflammatory bowel disease versus lymphoma in the ferret (Mustela putorius furo).

PubMed

Watson, Megan K; Cazzini, Paola; Mayer, Joerg; Gottdenker, Nicole; Reavill, Drury; Parry, Nicola; Fox, James G; Sakamoto, Kaori

2016-05-01

Inflammatory bowel disease (IBD) is a common disorder of ferrets (Mustela putorius furo) that may progress to lymphoma. Although routine histology is used to distinguish between these diseases, misclassifications may occur. Immunohistochemistry (IHC) is commonly used to distinguish between IBD and lymphoma in small animals. The objective of our study was to determine the agreement in the diagnosis reached solely using hematoxylin and eosin (HE)-stained, full-thickness sections versus using a combination of HE and IHC. Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal lymphoma and 3 control ferrets were analyzed by pathologists with expertise in ferrets. A pathologist blinded to the original diagnosis assessed the same HE-stained sections. Analysis was then repeated using HE sections in parallel with sections stained using antibodies against CD3 and CD79a. No significant difference was found between the original HE diagnosis and the HE diagnosis reached by the blinded pathologist (p = 0.91) or between the blinded pathologist's HE versus HE with IHC diagnosis (p = 0.16). In the 2 cases where disagreement was present, IHC was pivotal in reaching a final diagnosis. There was no significant age (p = 0.29) difference between diagnoses; however, significantly more male ferrets were affected with IBD than females (p = 0.004). Immunophenotype of the lymphoma was not correlated with predilection for location in the intestinal wall (p = 0.44). Results suggest that although IHC is not necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be useful a definitive diagnosis in cases of severe IBD. © 2016 The Author(s).

Biomechanical remodeling of obstructed guinea pig jejunum

PubMed Central

Zhao, Jingbo; Liao, Donghua; Yang, Jian; Gregersen, Hans

2010-01-01

Data on morphological and biomechanical remodeling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days respectively. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cmH20. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner. PMID:20189575

Investigation of mucosal pattern of gastric antrum using magnifying narrow-band imaging in patients with chronic atrophic fundic gastritis.

PubMed

Yamasaki, Yasushi; Uedo, Noriya; Kanzaki, Hiromitsu; Kato, Minoru; Hamada, Kenta; Aoi, Kenji; Tonai, Yusuke; Matsuura, Noriko; Kanesaka, Takashi; Yamashina, Takeshi; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ishihara, Ryu; Tomita, Yasuhiko; Iishi, Hiroyasu

2017-01-01

Magnifying narrow-band imaging (M-NBI) can reportedly help predict the presence and distribution of atrophy and intestinal metaplasia in the gastric corpus. However, the micro-mucosal pattern of the antrum shown by M-NBI differs from that of the corpus. We studied the distribution and histology of the micro-mucosal pattern in the antrum based on magnifying endoscopy. Endoscopic images of the greater curvature of the antrum were evaluated in 50 patients with chronic atrophic fundic gastritis (CAFG). The extent of CAFG was evaluated by autofluorescence imaging. The micro-mucosal pattern was evaluated by M-NBI and classified into groove and white villiform types. The localization of white villiform type mucosa was classified into three types in relation to the areae gastricae : null, central, and segmental types. Biopsies were taken from regions showing different micro-mucosal patterns. Associations among the extent of CAFG, micro-mucosal pattern, and histology were examined. As the extent of CAFG increased, the proportion of white villiform type mucosa increased, whereas that of groove type mucosa decreased (P=0.022). In patients with extensive CAFG, most of the areae gastricae was composed of the segmental or central type of white villiform type mucosa (P=0.044). The white villiform type mucosa had significantly higher grades of atrophy (P=0.002) and intestinal metaplasia (P<0.001) than did the groove type mucosa. White villiform type mucosa is indicative of atrophy and intestinal metaplasia in the gastric antrum. It extends to the whole or central part of the areae gastricae as CAFG becomes more extensive.

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats.

PubMed

Motte, Jeremias; Ambrosius, Björn; Grüter, Thomas; Bachir, Hussein; Sgodzai, Melissa; Pedreiturria, Xiomara; Pitarokoili, Kalliopi; Gold, Ralf

2018-04-24

Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

Single-session endoscopic resection and focal radiofrequency ablation for short-segment Barrett's esophagus with early neoplasia.

PubMed

Barret, Maximilien; Belghazi, Kamar; Weusten, Bas L A M; Bergman, Jacques J G H M; Pouw, Roos E

2016-07-01

The management of early neoplasia in Barrett's esophagus (BE) requires endoscopic resection of visible lesions, followed by radiofrequency ablation (RFA) of the remaining BE. We evaluated the safety and efficacy of combining endoscopic resection and focal RFA in a single endoscopic session in patients with early BE neoplasia. This was a retrospective analysis of patients with early BE neoplasia and a visible lesion undergoing combined endoscopic resection and focal RFA in a single session. Consecutive ablation procedures were performed every 8 to 12 weeks until complete endoscopic and histologic eradication of dysplasia and intestinal metaplasia were reached. Forty patients were enrolled, with a median C1M2 BE segment, a visible lesion with a median diameter of 15 mm, and invasive carcinoma in 68% of cases. Endoscopic resection was performed by using the multiband mucosectomy technique in 80% of cases, and the Barrx(90) catheter (Barrx Medical, Sunnyvale, Calif) was used for focal ablation. When an intention-to-treat analysis was used, both complete remission of all neoplasia and intestinal metaplasia were 95% after a median follow-up of 19 months. Stenoses occurred in 33% of cases and were successfully managed with a median number of 2 dilations. In 43% of patients, 1 single-session treatment resulted in complete histologic remission of intestinal metaplasia. Combining endoscopic resection and focal RFA in a single session appears to be effective. Less-aggressive RFA regimens could limit the adverse event rates. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

PubMed Central

2014-01-01

Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Results Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels. Conclusion Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea. PMID:25095704

THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

PubMed

Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

2016-04-01

Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

Lauren classification and individualized chemotherapy in gastric cancer.

PubMed

Ma, Junli; Shen, Hong; Kapesa, Linda; Zeng, Shan

2016-05-01

Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.

Gist Manifesting As A Retroperitoneal Tumor – Clinicopathologic Immunohistochemical, and Molecular Genetic Study of 112 Cases

PubMed Central

Miettinen, Markku; Felisiak-Golabek, Anna; Wang, Zengfeng; Inaguma, Shingo; Lasota, Jerzy

2016-01-01

Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal tract, but some present apparently outside the GI-tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21-89 years). Based on clinically or histologically detected connections to GI-tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n = 25), pelvic (n = 11), mesenteric (n = 4), and of unspecified/miscellaneous sites (n = 35). The tumors varied in size 3-35 cm (median, 15 cm) and by mitotic rate per 5 mm2, 0- >100 (median 10). Histologically the tumors apparently arising outside the GI-tract had features of intestinal (n = 41) and gastric GISTs (n = 25); 9 cases had indeterminate histology. The histologic variants included spindled, epithelioid, vacuolated, nested and myxoid potentially simulating other tumors such as liposarcoma and solitary fibrous tumor. Most GISTs were KIT-positive (106/112 cases), and the remaining 6 tumors were Dog1/Ano1-positive. Five cases showed focal nuclear positivity for MDM2. KIT mutations were detected in 42/59 cases, and PDGFRA mutations in 4/16 KIT wild-type and 3/5 of the KIT-negative tumors analyzed. One pelvic retroperitoneal GIST was SDH-deficient. All 79 patients were dead at last follow-up with a median survival of 14 months, with few survivals > 5 years. Only operable vs. inoperable tumor was a statistically favorable factor in univariate analysis (p<0.01). In multivariate analysis, mitotic rate > 50/5 mm2 was significant for a shorter survival (HR 5.25, 95% CI 1.65-16.8., p<0.01). Histologic and clinicopathologic similarity of extragastrointestinal retroperitoneal GISTs with GISTs of GI-tract suggests their GI tract origin. Potentially overlapping features between GIST and other retroperitoneal tumors necessitate use of multiple diagnostic markers and molecular genetic studies. PMID:28288036

Intestinal ischemia/reperfusion injury triggers activation of innate toll-like receptor 4 and adaptive chemokine programs.

PubMed

Watson, M J; Ke, B; Shen, X-D; Gao, F; Busuttil, R W; Kupiec-Weglinski, J W; Farmer, D G

2008-12-01

Ischemia/reperfusion injury (IRI) is a major problem in intestinal transplantation. Toll-like receptor 4 (TLR4) has been implicated as a possible link between the innate and adaptive immune systems, however little data exists regarding TLR4 in intestinal IRI. The goal of this study is to evaluate the involvement of TLR4 in intestinal IRI and to assess the effect on T cell related chemokine programs. C57BL6 mice underwent 100 minutes of warm intestinal ischemia by SMA clamping. Control WT mice underwent laparotomy without vascular occlusion. Separate survival and analysis groups were performed, and intestinal tissue was harvested at 1 hour, 2 hours, 4 hours, and 24 hours post-reperfusion. Analysis included histology, CD3 immunostaining, myeloperoxidase activity, Western blot, and PCR. Survival was significantly worse in the IRI group vs control (50% vs. 100%). IRI caused severe histopathological injury including mucosal erosions and villous congestion and hemorrhage. Myeloperoxidase activity increased in a time-dependent manner after IRI (2.71 0.25 at 1 hour, 2.92 0.25 at 2 hours, 4 0.16 at 4 hours, 5.1 0.25 at 24 hours vs 0.47 0.11 controls, P < .05). Protein expression of TLR4 followed by NF-kappaB was increased after IRI. Additionally, mRNA production of IP-10, MIP-2, MCP-1, and RANTES was increased at all time-points, as was mRNA for ICAM-1 and E-selectin. This study is the first to demonstrate increased expression of TLR4 and NF-kappaB after warm intestinal IRI. This detrimental cascade may be initiated by TLR4 via NF-kappaB signaling pathways, implicating TLR4 as a potential therapeutic target for the prevention of intestinal IRI.

Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels.

PubMed

Moghadamrad, Sheida; McCoy, Kathy D; Geuking, Markus B; Sägesser, Hans; Kirundi, Jorum; Macpherson, Andrew J; De Gottardi, Andrea

2015-05-01

Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH. © 2015 by the American Association for the Study of Liver Diseases.

Histomorphometry and macroscopic intestinal lesions in broilers infected with Eimeria acervulina.

PubMed

Assis, R C L; Luns, F D; Beletti, M E; Assis, R L; Nasser, N M; Faria, E S M; Cury, M C

2010-03-25

This study aimed at measuring intestinal villi and assessing the intestinal absorptive area in broilers infected with Eimeria acervulina under different treatments to control coccidiosis. The experiment was divided into two stages, carried out in successive housings, raised in the same environment (or aviary). In the first stage, on 25 May 2008, fifty 12-day-old birds were orally inoculated with 3 x 10(3) oocysts of E. acervulina. In the second stage, on July 2008, other 50 birds were allocated on litter contaminated by the feces of birds on the first housing (natural infection by oocysts present in the reused litter). The experiment was arranged in a complete randomized design with five treatments and three replicates of 10 chicks per treatment. Broiler chicks were housed at 1 day of age and autopsies were performed at 21 days of age. Three 2-cm-long segments of the duodenum were excised from each bird and fixed in 10% buffered formalin. A total of 30 slides were prepared for each treatment, totaling 150 evaluated histological sections using H&E staining. Villus morphology was carried out by the HL Image 97 software. The intestinal absorptive area was calculated and macroscopic lesions were classified according to standard lesion scores. Results showed that intestinal villus measurements and absorptive area are directly affected by E. acervulina and that there is direct and positive correlation between the macro and microscopic findings observed in intestinal coccidiosis. E. acervulina causes shortening of villi and reduction in the intestinal absorptive area, affecting broiler growth. The prevention method of litter fermentation during the interval between housings and oral administration of Diclazuril can reduce the severity of intestinal lesions by E. acervulina in broilers impairing oocyst virulence or viability.

Microscale spatial analysis provides evidence for adhesive monopolization of dietary nutrients by specific intestinal bacteria

PubMed Central

Takada, Toshihiko; Nagata, Yuriko; Kado, Shoichi; Kushiro, Akira

2017-01-01

Each species of intestinal bacteria requires a nutritional source to maintain its population in the intestine. Dietary factors are considered to be major nutrients; however, evidence directly explaining the in situ utilization of dietary factors is limited. Microscale bacterial distribution would provide clues to understand bacterial lifestyle and nutrient utilization. However, the detailed bacterial localization around dietary factors in the intestine remains uninvestigated. Therefore, we explored microscale habitats in the murine intestine by using histology and fluorescent in situ hybridization, focusing on dietary factors. This approach successfully revealed several types of bacterial colonization. In particular, bifidobacterial colonization and adhesion on granular starch was frequently and commonly observed in the jejunum and distal colon. To identify the bacterial composition of areas around starch granules and areas without starch, laser microdissection and next-generation sequencing-based 16S rRNA microbial profiling was performed. It was found that Bifidobacteriaceae were significantly enriched by 4.7 fold in peri-starch areas compared to ex-starch areas. This family solely consisted of Bifidobacterium pseudolongum. In contrast, there was no significant enrichment among the other major families. This murine intestinal B. pseudolongum had starch-degrading activity, confirmed by isolation from the mouse feces and in vitro analysis. Collectively, our results demonstrate the significance of starch granules as a major habitat and potential nutritional niche for murine intestinal B. pseudolongum. Moreover, our results suggest that colonizing bifidobacteria effectively utilize starch from the closest location and maintain the location. This may be a bacterial strategy to monopolize solid dietary nutrients. We believe that our analytical approach could possibly be applied to other nutritional factors, and can be a powerful tool to investigate in vivo relationships between bacteria and environmental factors in the intestine. PMID:28394924

Microscale spatial analysis provides evidence for adhesive monopolization of dietary nutrients by specific intestinal bacteria.

PubMed

Nagara, Yusuke; Takada, Toshihiko; Nagata, Yuriko; Kado, Shoichi; Kushiro, Akira

2017-01-01

Each species of intestinal bacteria requires a nutritional source to maintain its population in the intestine. Dietary factors are considered to be major nutrients; however, evidence directly explaining the in situ utilization of dietary factors is limited. Microscale bacterial distribution would provide clues to understand bacterial lifestyle and nutrient utilization. However, the detailed bacterial localization around dietary factors in the intestine remains uninvestigated. Therefore, we explored microscale habitats in the murine intestine by using histology and fluorescent in situ hybridization, focusing on dietary factors. This approach successfully revealed several types of bacterial colonization. In particular, bifidobacterial colonization and adhesion on granular starch was frequently and commonly observed in the jejunum and distal colon. To identify the bacterial composition of areas around starch granules and areas without starch, laser microdissection and next-generation sequencing-based 16S rRNA microbial profiling was performed. It was found that Bifidobacteriaceae were significantly enriched by 4.7 fold in peri-starch areas compared to ex-starch areas. This family solely consisted of Bifidobacterium pseudolongum. In contrast, there was no significant enrichment among the other major families. This murine intestinal B. pseudolongum had starch-degrading activity, confirmed by isolation from the mouse feces and in vitro analysis. Collectively, our results demonstrate the significance of starch granules as a major habitat and potential nutritional niche for murine intestinal B. pseudolongum. Moreover, our results suggest that colonizing bifidobacteria effectively utilize starch from the closest location and maintain the location. This may be a bacterial strategy to monopolize solid dietary nutrients. We believe that our analytical approach could possibly be applied to other nutritional factors, and can be a powerful tool to investigate in vivo relationships between bacteria and environmental factors in the intestine.

Oral administration of thymoquinone mitigates the effect of cisplatin on brush border membrane enzymes, energy metabolism and antioxidant system in rat intestine.

PubMed

Shahid, Faaiza; Farooqui, Zeba; Abidi, Subuhi; Parwez, Iqbal; Khan, Farah

2017-10-01

Cisplatin (CP) is a widely used chemotherapeutic agent that elicits severe gastrointestinal toxicity. Nigella sativa, a member of family Ranunculaceae, is one of the most revered medicinal plant known for its numerous health benefits. Thymoquinone (TQ), a major bioactive component derived from the volatile oil of Nigella sativa seeds, has been shown to improve gastrointestinal functions in animal models of acute gastric/intestinal injury. In view of this, the aim of the present study was to investigate the protective effect of TQ on CP induced toxicity in rat intestine and to elucidate the mechanism underlying these effects. Rats were divided into four groups viz. control, CP, TQ and CP+TQ. Animals in CP+TQ and TQ groups were orally administered TQ (1.5mg/kg bwt) with and without a single intraperitoneal dose of CP (6mg/kg bwt) respectively. The effect of TQ was determined on CP induced alterations in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in rat intestine. TQ administration significantly mitigated CP induced decline in the specific activities of BBM marker enzymes, both in the mucosal homogenates and in the BBM vesicles (BBMV) prepared from intestinal mucosa. Furthermore, TQ administration restored the redox and metabolic status of intestinal mucosal tissue in CP treated rats. The biochemical results were supported by histopathological findings that showed extensive damage to intestine in CP treated rats and markedly preserved intestinal histoarchitecture in CP and TQ co-treated group. The biochemical and histological data suggest a protective effect of TQ against CP-induced gastrointestinal damage. Thus, TQ may have a potential for clinical application to counteract the accompanying gastrointestinal toxicity in CP chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas.

PubMed

Almeida, Raquel; Silva, Elisabete; Santos-Silva, Filipe; Silberg, Debra G; Wang, Jiangfu; De Bolós, Carmen; David, Leonor

2003-01-01

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway. Copyright 2002 John Wiley & Sons, Ltd.

Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

PubMed

Duman, Deniz Güney; Kumral, Zarife Nigâr Özdemir; Ercan, Feriha; Deniz, Mustafa; Can, Güray; Cağlayan Yeğen, Berrak

2013-08-28

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.

PubMed

Yasutomi, Eiichiro; Hoshi, Namiko; Adachi, Soichiro; Otsuka, Takafumi; Kong, Lingling; Ku, Yuna; Yamairi, Haruka; Inoue, Jun; Ishida, Tsukasa; Watanabe, Daisuke; Ooi, Makoto; Yoshida, Masaru; Tsukimi, Tomoya; Fukuda, Shinji; Azuma, Takeshi

2018-04-01

Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats.

PubMed

Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y; Owyang, Chung

2014-02-01

Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction (PCR) and 454 pyrosequencing were used to analyze bacterial 16S ribosomal RNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

PubMed

Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet

2017-11-15

Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary intestinal lymphangiectasia (Waldmann's disease).

PubMed

Vignes, Stéphane; Bellanger, Jérôme

2008-02-22

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.

Primary intestinal lymphangiectasia (Waldmann's disease)

PubMed Central

Vignes, Stéphane; Bellanger, Jérôme

2008-01-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur. PMID:18294365

Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model.

PubMed

Sukhotnik, Igor; Ben Shahar, Yoav; Halabi, Salim; Bitterman, Nir; Dorfman, Tatiana; Pollak, Yulia; Coran, Arnold; Bitterman, Arie

2018-01-05

 Accumulating evidence indicates that changes in intestinal toll-like receptors (TLRs) precede histological injury in a rodent model of necrotizing enterocolitis. N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. A recent study has shown that treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal ischemia-reperfusion (IR). The objective of this study was to determine the effects of NAS on TLR-4, myeloid differentiation factor 88 (Myd88), and TNF-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following intestinal IR in a rat.  Male Sprague-Dawley rats were randomly assigned to one of the four experimental groups: 1) Sham rats underwent laparotomy; 2) Sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); 3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 minutes followed by 48 hours of reperfusion; and 4) IR-NAS rats underwent IR and were treated with IP NAS immediately before abdominal closure. Intestinal structural changes, mucosal TLR-4, MyD88, and TRAF6 mucosal gene, and protein expression were examined using real-time PCR, Western blot, and immunohistochemistry.  Significant mucosal damage in IR rats was accompanied by a significant upregulation of TLR-4, MyD88, and TRAF6 gene and protein expression in intestinal mucosa compared with control animals. The administration of NAS decreased the intestinal injury score, inhibited cell apoptosis, and significantly reduced the expression of TLR-4, MyD88, and TRAF6.  Treatment with NAS is associated with downregulation of TLR-4, MyD88, and TRAF6 expression along with a concomitant decrease in intestinal mucosal injury caused by intestinal IR in a rat. Georg Thieme Verlag KG Stuttgart · New York.

EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS.

PubMed

Xiao, Guizhen; Yuan, Fangfang; Geng, Yan; Qiu, Xiaowen; Liu, Zhifeng; Lu, Jiefu; Tang, Liqun; Zhang, Yali; Su, Lei

2015-10-01

Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37°C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography-mass selective detector. Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells. Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.

Intestinal lesions in dogs with acute hemorrhagic diarrhea syndrome associated with netF-positive Clostridium perfringens type A.

PubMed

Leipig-Rudolph, Miriam; Busch, Kathrin; Prescott, John F; Mehdizadeh Gohari, Iman; Leutenegger, Christian M; Hermanns, Walter; Wolf, Georg; Hartmann, Katrin; Verspohl, Jutta; Unterer, Stefan

2018-04-01

Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex. Endoscopic biopsies of the gastrointestinal tract were taken and examined histologically (H&E, Giemsa), immunohistochemically ( Clostridium spp., parvovirus), and bacteriologically. The main findings were acute necrotizing and neutrophilic enterocolitis (9 of 10) with histologic detection of clostridia-like, gram-positive bacteria on the necrotic mucosal surface (9 of 10). Clostridium perfringens isolated from the duodenum was identified as type A (5 of 5) by multiplex PCR (5 of 5). In addition, each of the 5 genotyped isolates encoded the pore-forming toxin netF. Clostridium spp. (not C. perfringens) were cultured from duodenal biopsies in 2 of 9 control dogs. These findings suggest that the pore-forming netF toxin is responsible for the necrotizing lesions in the intestines of a significant proportion of dogs with AHDS. Given that the stomach was not involved in the process, the term "acute hemorrhagic diarrhea syndrome" seems more appropriate than the frequently used term "hemorrhagic gastroenteritis."

Histology of a Woolly Mammoth (Mammuthus primigenius) Preserved in Permafrost, Yamal Peninsula, Northwest Siberia.

PubMed

Papageorgopoulou, Christina; Link, Karl; Rühli, Frank J

2015-06-01

In 2007, the baby woolly mammoth (Mammuthus primigenius) named Lyuba was found frozen in the Siberian tundra permafrost along the Yuribey River. She was proclaimed the best-preserved mammoth discovery. As part of the endoscopic examination of Lyuba, tissue samples of hair, muscle, and internal organs were taken. The sectioned biopsies were stained using standard and special histological stains. In general, the microscopic preservation of the tissue was good although no clearly identifiable cell nuclei were found by standard staining methods. Only a few cell nuclei could be identified in some samples when fluorescence stained with DAPI. The best-preserved structures were collagen fibers and muscle tissue, which gave some structural resemblance to the organs. In the hairs, evidence of pigmentation, a scaly surface, diagonal intra-hair structures, and a medulla were seen. Fat droplets could be identified with Sudan Red in the subcutaneous fat sample and in several organs. Bacteria were seen on the lumen side of the small intestine and caecum, and in the liver and lung tissue. In addition, fungi and pollen were seen in the lung sample. In the wall of the caecum and small intestine, blood vessels and nerves were visualized. Iron was identified in the vivianite sample. Some biopsies compared well structurally with the African elephant tissue sections. The histological findings support the theory that Lyuba drowned in muddy water. The microscopic tissue preservation and cell nuclei destruction indicate that Lyuba's body underwent at least one freeze-thaw cycle. © 2015 Wiley Periodicals, Inc.

Heterotrimeric G Stimulatory Protein α Subunit Is Required for Intestinal Smooth Muscle Contraction in Mice.

PubMed

Qin, Xiaoteng; Liu, Shangming; Lu, Qiulun; Zhang, Meng; Jiang, Xiuxin; Hu, Sanyuan; Li, Jingxin; Zhang, Cheng; Gao, Jiangang; Zhu, Min-Sheng; Feil, Robert; Li, Huashun; Chen, Min; Weinstein, Lee S; Zhang, Yun; Zhang, Wencheng

2017-04-01

The α subunit of the heterotrimeric G stimulatory protein (Gsa), encoded by the guanine nucleotide binding protein, α-stimulating gene (Gnas, in mice), is expressed ubiquitously and mediates receptor-stimulated production of cyclic adenosine monophosphate and activation of the protein kinase A signaling pathway. We investigated the roles of Gsa in vivo in smooth muscle cells of mice. We performed studies of mice with Cre recombinase-mediated disruption of Gnas in smooth muscle cells (Gsa SMKO and SM22-CreER T2 , induced in adult mice by tamoxifen). Intestinal tissues were collected for histologic, biochemical, molecular, cell biology, and physiology analyses. Intestinal function was assessed in mice using the whole-gut transit time test. We compared gene expression patterns of intestinal smooth muscle from mice with vs without disruption of Gnas. Biopsy specimens from ileum of patients with chronic intestinal pseudo-obstruction and age-matched control biopsies were analyzed by immunohistochemistry. Disruption of Gnas in smooth muscle of mice reduced intestinal motility and led to death within 4 weeks. Tamoxifen-induced disruption of Gnas in adult mice impaired contraction of intestinal smooth muscle and peristalsis. More than 80% of these died within 3 months of tamoxifen exposure, with features of intestinal pseudo-obstruction characterized by chronic intestinal dilation and dysmotility. Gsa deficiency reduced intestinal levels of cyclic adenosine monophosphate and transcriptional activity of the cyclic adenosine monophosphate response element binding protein 1 (CREB1); this resulted in decreased expression of the forkhead box F1 gene (Foxf1) and protein, and contractile proteins, such as myosin heavy chain 11; actin, α2, smooth muscle, aorta; calponin 1; and myosin light chain kinase. We found decreased levels of Gsa, FOXF1, CREB1, and phosphorylated CREB1 proteins in intestinal muscle layers of patients with chronic intestinal pseudo-obstruction, compared with tissues from controls. Gsa is required for intestinal smooth muscle contraction in mice, and its levels are reduced in ileum biopsies of patients with chronic intestinal pseudo-obstruction. Mice with disruption of Gnas might be used to study human chronic intestinal pseudo-obstruction. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms.

PubMed

Bozzola, Mauro; Meazza, Cristina; Gertosio, Chiara; Pagani, Sara; Larizza, Daniela; Calcaterra, Valeria; Luinetti, Ombretta; Farello, Giovanni; Tinelli, Carmine; Iughetti, Lorenzo

2017-07-15

The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines. In this retrospective study a total of 105 patients, suspected of having CD because of extra-intestinal symptoms and showing serum tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) measurements and HLA genotyping, were considered for the final analysis (33 boys and 72 girls; age range 1.5-17.6 years). Histological findings confirmed diagnosis of CD in 97 (92.4%) patients. Forty-one patients (39%) showed anti-tTG >10 times normal values, positive EMA and positive HLA-DQ2/DQ8 (positive TT). All of them had a diagnosis of CD, therefore there were no false positive cases. Sixty-four patients were negative for the TT. In eight cases, CD was ruled out and these were considered true negative cases. In the remaining 56 negative TT patients, intestinal biopsy confirmed CD diagnosis and they were considered false negatives. Based on these results, specificity for the TT was 100% and sensitivity was 42.3%. On the basis of the present study, diagnosis of CD can be reliably performed without a duodenal biopsy in children with only extra-intestinal symptoms.

Precision resection of intestine using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Beck, Rainer J.; Gora, Wojciech S.; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

2016-03-01

Endoscopic resection of early colorectal neoplasms typically employs electrocautery tools, which lack precision and run the risk of full thickness thermal injury to the bowel wall with subsequent perforation. We present a means of endoluminal colonic ablation using picosecond laser pulses as a potential alternative to mitigate these limitations. High intensity ultrashort laser pulses enable nonlinear absorption processes, plasma generation, and as a consequence a predominantly non-thermal ablation regimen. Robust process parameters for the laser resection are demonstrated using fresh ex vivo pig intestine samples. Square cavities with comparable thickness to early colorectal neoplasms are removed for a wavelength of 1030 nm and 515 nm using a picosecond laser system. The corresponding histology sections exhibit in both cases only minimal collateral damage to the surrounding tissue. The ablation depth can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers for the resection of intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional electrocautery.

Effects of dietary fermentation concentrate of Hericium caput-medusae (Bull.:Fr.) Pers. on growth performance, digestibility, and intestinal microbiology and morphology in broiler chickens.

PubMed

Shang, Hong Mei; Song, Hui; Xing, Ya Li; Niu, Shu Li; Ding, Guo Dong; Jiang, Yun Yao; Liang, Feng

2016-01-15

The present study was undertaken to investigate the effects of fermentation concentrate of Hericium caput-medusae (Bull.:Fr.) Pers. (HFC) on growth performance, digestibility, intestinal microbiology, and intestinal morphology in broiler chickens. A total of 600 male Arbor Acres broilers were randomly divided into five dietary treatments (20 broilers per pen with six pens per treatment): CON (basal diet), ANT (basal diet supplemented with 5 mg kg(-1) flavomycin) and HFC (basal diet supplemented with 6, 12, and 18 g kg(-1) HFC). The experimental lasted for 42 days. The results revealed that the average daily gain [linear (L), P < 0.01; quadratic (Q), P < 0.01] of broilers increased when the HFC levels increased during the starter (days 1-21), finisher (days 22-42), and the overall experiment period (days 1 to 42). In the small intestinal digesta and the caecum digesta, the Escherichia coli count (L, P < 0.05; Q, P < 0.001) decreased while the Lactobacilli count (L, P < 0.01; Q, P < 0.001) and Bifidobacteria count (L, P < 0.001; Q, P < 0.001) increased when the HFC levels increased. The crude protein digestibility of broilers (L, P < 0.01; Q, P < 0.001) increased when the HFC levels increased. In the duodenum, jejunum, and ileum of broilers, the villus height and villus height to crypt depth ratio (L, P < 0.001; Q, P < 0.001) increased when the HFC levels increased. Dietary supplementation with HFC increased gut Lactobacilli and Bifidobacteria counts and inhibited E. coli growth, improved nutrient utilisation and intestine villus structure, and thus improved the growth of broilers. © 2015 Society of Chemical Industry.

Whipple's disease. Report of five cases with different clinical features.

PubMed

Ferrari, M de L; Vilela, E G; Faria, L C; Couto, C A; Salgado, C J; Leite, V R; Brasileiro Filho, G; Bambirra, E A; Mendes, C M; Carvalho, S de C; de Oliveira, C A; da Cunha, A S

2001-01-01

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine.

PubMed

Ansari, Fariheen Aisha; Ali, Shaikh Nisar; Arif, Hussain; Khan, Aijaz Ahmed; Mahmood, Riaz

2017-01-01

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

Effect of tannins on growth performance and intestinal ecosystem in weaned piglets.

PubMed

Biagia, Giacomo; Cipollini, Irene; Paulicks, Brigitte R; Roth, Franz X

2010-04-01

Tannins are natural polyphenolic compounds that can reduce digestibility of dietary protein but also display antibacterial effects. The present study investigated, in vitro and in vivo, the effect of different levels of tannins (using a chestnut wood extract containing 75% tannins) on growth performance, intestinal microbiota and wall morphology in piglets. During a 24 h in vitro caecal fermentation, the utilisation of tannins at 0.75, 1.5, 3, and 6 g/l significantly reduced total gas production and concentrations of ammonia and volatile fatty acids and increased viable counts of enterococci and coliforms. When fed to piglets at 1.13, 2.25, and 4.5 g/kg, tannins significantly improved feed efficiency and reduced caecal concentrations of ammonia, iso-butyric, and iso-valeric acid. Viable counts of lactobacilli tended to be increased by tannins in the jejunum, while bacterial caecal counts were not affected. Depth of ileal crypts tended to decrease in piglets fed tannins at 2.25 and 4.5 g/kg. The present study showed that feeding weaned piglets with a tannin-rich wood extract can result in improved feed efficiency and reduction of intestinal bacterial proteolytic reactions. The growth-enhancing effect that tannins had on enterococci and coliforms under in vitro conditions deserves further investigation.

A histological atlas of the tissues and organs of neotenic and metamorphosed axolotl.

PubMed

Demircan, Turan; İlhan, Ayşe Elif; Aytürk, Nilüfer; Yıldırım, Berna; Öztürk, Gürkan; Keskin, İlknur

2016-09-01

Axolotl (Ambystoma Mexicanum) has been emerging as a promising model in stem cell and regeneration researches due to its exceptional regenerative capacity. Although it represents lifelong lasting neoteny, induction to metamorphosis with thyroid hormones (THs) treatment advances the utilization of Axolotl in various studies. It has been reported that amphibians undergo anatomical and histological remodeling during metamorphosis and this transformation is crucial for adaptation to terrestrial conditions. However, there is no comprehensive histological investigation regarding the morphological alterations of Axolotl organs and tissues throughout the metamorphosis. Here, we reveal the histological differences or resemblances between the neotenic and metamorphic axolotl tissues. In order to examine structural features and cellular organization of Axolotl organs, we performed Hematoxylin & Eosin, Luxol-Fast blue, Masson's trichrome, Alcian blue, Orcein and Weigart's staining. Stained samples from brain, gallbladder, heart, intestine, liver, lung, muscle, skin, spleen, stomach, tail, tongue and vessel were analyzed under the light microscope. Our findings contribute to the validation of the link between newly acquired functions and structural changes of tissues and organs as observed in tail, skin, gallbladder and spleen. We believe that this descriptive work provides new insights for a better histological understanding of both neotenic and metamorphic Axolotl tissues. Copyright © 2016 Elsevier GmbH. All rights reserved.

Gastritis: the histology report.

PubMed

Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco

2011-03-01

Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

[Effect of somatostatin-14 in simple mechanical obstruction of the small intestine].

PubMed

Jimenez-Garcia, A; Ahmad Araji, O; Balongo Garcia, R; Nogales Munoz, A; Salguero Villadiego, M; Cantillana Martinez, J

1994-02-01

In order to investigate the properties of somatostatin-14 we studied an experimental model of simple mechanical and closed loop occlusion. Forty-eight New Zealand rabbits were assigned randomly to three groups of 16: group C (controls) was operated and treated with saline solution (4 cc/Kg/h); group A was operated and initially treated with saline solution and an equal dose of somatostatin-14 (3.5 micrograms/Kg/h; and group B was operated and treated in the same manner as group A, but later, 8 hours after the laparotomy. The animals were sacrificed 24 hours later; intestinal secretion was quantified, blood and intestinal fluid chemistries were performed and specimens of the intestine were prepared for histological examination. Descriptive statistical analysis of the results was performed with the ANOVA, a semi-quantitative test and the covariance test. Somatostatin-14 produced an improvement in the volume of intestinal secretion in the treated groups compared with the control group. The results were statistically significant in group B treated after an 8-hour delay: closed loop (ml): 6.40 +/- 1.12, 2.50 +/- 0.94, 1.85 +/- 0.83 and simple mechanical occlusion (ml): 175 +/- 33.05, 89.50 +/- 9.27, 57.18 +/- 21.23, p < 0.01 for groups C, A and B C, A and B respectively. Net secretion of Cl and Na ions was also improved, p < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

[BOWEL ENDOMETRIOSIS - CASE OF RECTAL LOCALISATION.

PubMed

Tsankov, Ts; Zlatkov, V

Endometriosis is a relatively common disease which rarely involves the bowel, and even more rarely occurs with intestinal obstruction. Gastrointestinal tract is involved in 3 to 37% of women with endometriosis such as the frequency is highest in the rectum and the sigma (72%), small intestine (7%), cecum (3.6%) and others. Our case concerns 49 years old woman with a picture of secondary intestinal obsruction, deepening during the last 2-3 months. An anterior resection of the rectum with the closure of the rectal stump has been performed with temporary colostoma - due to the severely inflamed and distended colon as a result of stenosis about 1 cm in diameter involving the portion from the Bauhin's valve to the rectal ampula, caused by two fist-sized tumors in the intestinal wall - on the rear and rear-left side of the rectum. Distally, about 2-3 cm of the tumors, on the anterior wall of the rectum have been found two plaque-like lesions, additionally. The histological result showed that the wall of the colon is engaged by transmural endometriosis, involving the mucosa, muskularis propria and serosa. The case presented differential diagnostic difficulties to exclude malignancy. The benefits of surgical treatment of intestinal endometriosis despite the significant volume of conducted surgery should not be underestimated, as with medication, it significantly improves clinical symptoms and quality of life.

Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a−/− mice

PubMed Central

Dommels, Y. E.M.; Zhu, S.; Davy, M.; Martell, S.; Hedderley, D.; Barnett, M. P.G.; McNabb, W. C.; Roy, N. C.

2007-01-01

Multidrug resistance targeted mutation (mdr1a−/−) mice spontaneously develop intestinal inflammation. The aim of this study was to further characterize the intestinal inflammation in mdr1a−/− mice. Intestinal samples were collected to measure inflammation and gene expression changes over time. The first signs of inflammation occurred around 16 weeks of age and most mdr1a−/− mice developed inflammation between 16 and 27 weeks of age. The total histological injury score was the highest in the colon. The inflammatory lesions were transmural and discontinuous, revealing similarities to human inflammatory bowel diseases (IBD). Genes involved in inflammatory response pathways were up-regulated whereas genes involved in biotransformation and transport were down-regulated in colonic epithelial cell scrapings of inflamed mdra1−/− mice at 25 weeks of age compared to non-inflamed FVB mice. These results show overlap to human IBD and strengthen the use of this in vivo model to study human IBD. The anti-inflammatory regenerating islet-derived genes were expressed at a lower level during inflammation initiation in non-inflamed colonic epithelial cell scrapings of mdr1a−/− mice at 12 weeks of age. This result suggests that an insufficiently suppressed immune response could be crucial to the initiation and development of intestinal inflammation in mdr1a−/− mice. PMID:18850176

Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.

PubMed

Tatsuta, A; Iishi, H; Baba, M; Yano, H; Murata, K; Mukai, M; Akedo, H

2000-01-01

The effect of a naturally occurring flavonoid apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression. Our findings indicate that apigenin inhibits cancer metastasis through inhibition of phosphorylation of MAPK.

Intestinal lymphangiectasia in adults.

PubMed

Freeman, Hugh James; Nimmo, Michael

2011-02-15

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

Intestinal lymphangiectasia in adults

PubMed Central

Freeman, Hugh James; Nimmo, Michael

2011-01-01

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and “secondary” changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple’s disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn’s disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited. PMID:21364842

Chronic gastritis with intestinal metaplasia: clinico-statistical, histological and immunohistochemical study.

PubMed

Dîrnu, Rodica; Secureanu, F A; Neamţu, Carmen; Totolici, B D; Pop, O T; Mitruţ, P; Mălăescu, D Gh; Mogoantă, L

2012-01-01

Chronic gastritis has a high incidence in adults, causing progressive destruction of glandular structures, favoring the development of gastric atrophy. The association of chronic gastritis with intestinal type metaplasia of gastric mucosa has a poor outcome as intestinal metaplasia is regarded as a precancerous lesion. Metaplasia is common in patients with Helicobacter pylori infection and also heavy smokers. The aim of our study was to evaluate the relationship between chronic gastritis and intestinal metaplasia. The study was conducted on a total of 1218 patients, aged between 5 and 90 years, who presented for dyspeptic disorders in the period 2007-2010 and were examined clinically and endoscopically. During the gastroscopic examination, fragments of gastric mucosa were collected for the histopathological study and for highlighting the H. pylori infection. For the histopathological study, the Hematoxylin-Eosin and PAS-Alcian Blue stains were performed, while for the immunohistochemical study the anti-TAG72 and anti-PCNA antibodies were used. A diagnosis of gastritis was established in 615 patients, representing approximately 50.5% of all cases. Most cases with gastritis were found in people of middle age. Gastritis was present in almost all age groups, from teenagers to the elders. Of the 615 cases of gastritis, urease test was positive in 353 patients, representing approximately 57.40% of all patients with gastritis. Histopathological examination identified the presence of intestinal metaplasia in 61.60% of patients with chronic gastritis, mostly complete metaplasia. PCNA immunohistochemistry revealed that cell proliferation processes are intensified in intestinal metaplasia. This study highlights the importance of chronic gastritis, intestinal metaplasia, and H. pylori infection in the etiopathogeny of gastric cancer.

Supplementing formula-fed piglets with a low molecular weight fraction of bovine colostrum whey results in an improved intestinal barrier.

PubMed

De Vos, M; Huygelen, V; Van Raemdonck, G; Willemen, S; Fransen, E; Van Ostade, X; Casteleyn, C; Van Cruchten, S; Van Ginneken, C

2014-08-01

To test the hypothesis that a low molecular weight fraction of colostral whey could affect the morphology and barrier function of the small intestine, 30 3-d-old piglets (normal or low birth weight) were suckled (n = 5), artificially fed with milk formula (n = 5), or artificially fed with milk formula with a low molecular weight fraction of colostral whey (n = 5) until 10 d of age. The small intestine was sampled for histology (haematoxylin and eosin stain; anti-KI67 immunohistochemistry) and enzyme activities (aminopeptidase A, aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase, and sucrase). In addition, intestinal permeability was evaluated via a dual sugar absorption test and via the measurement of occludin abundance. Artificially feeding of piglets reduced final BW (P < 0.001), villus height (P < 0.001), lactase (P < 0.001), and dipeptidylpeptidase IV activities (P < 0.07), whereas crypt depth (P < 0.001) was increased. No difference was observed with regard to the permeability measurements when comparing artificially fed with naturally suckling piglets. Supplementing piglets with the colostral whey fraction did not affect BW, enzyme activities, or the outcome of the dual sugar absorption test. On the contrary, the small intestines of supplemented piglets had even shorter villi (P = 0.001) than unsupplemented piglets and contained more occludin (P = 0.002). In conclusion, at 10 d of age, no differences regarding intestinal morphology and permeability measurements were observed between the 2 BW categories. In both weight categories, the colostral whey fraction affected the morphology of the small intestine but did not improve the growth performances or the in vivo permeability. These findings should be acknowledged when developing formulated milk for neonatal animals with the aim of improving the performance of low birth weight piglets.

A Comparison of mucosal surface area and villous histology in small intestines of the Brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus).

PubMed

Zhang, Zhi-Qiang; Brun, Antonio; Price, Edwin R; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

2015-01-01

Studies on birds have led to the hypothesis that increased intestinal absorption between enterocytes (paracellular) evolved as a compensation for smaller intestinal size in fliers, which was perhaps selected to minimize the mass of digesta carried. This hypothesis predicts that bats will also exhibit relatively reduced intestinal size and high paracellular absorption, compared with nonflying mammals. Published studies on three bat species indicate relatively high paracellular absorption. One mechanism for increasing paracellular absorption per cm2 small intestine (SI) is increased number of tight junctions (TJs) across which paracellular absorption occurs. To our knowledge, we provide the first comparative analysis of enterocyte size and number in flying and nonflying mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared with Mus musculus using hematoxylin and eosin staining method. Bats had shorter and narrower SIs than mice, and after correction for body size difference by normalizing to mass3/4, the bats had 40% less nominal surface area than the mouse, as predicted. Villous enhancement of surface area was 90% greater in the bat than in the mouse, mainly because of longer villi and a greater density of villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of enterocytes per cm2 of the nominal surface area of the SI. Therefore, an increased density of TJs per cm2 SI may be a mechanistic explanation that helps to understand the high paracellular absorption observed in bats compared to nonflying mammals. © 2014 Wiley Periodicals, Inc.

Alterations in the small intestinal wall and motor function after repeated cisplatin in rat.

PubMed

Uranga, J A; García-Martínez, J M; García-Jiménez, C; Vera, G; Martín-Fontelles, M I; Abalo, R

2017-07-01

Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin. Male Wistar rats received saline or cisplatin (2 mg kg -1  week -1 , for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR. Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent). Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated. © 2017 John Wiley & Sons Ltd.

The healing effect of bone marrow-derived stem cells in acute radiation syndrome.

PubMed

Mortazavi, Seyed Mohammad Javad; Shekoohi-Shooli, Fatemeh; Aghamir, Seyed Mahmood Reza; Mehrabani, Davood; Dehghanian, Amirreza; Zare, Shahrokh; Mosleh-Shirazi, Mohammad Amin

2016-01-01

To determine the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on regeneration of bone marrow and intestinal tissue and survival rate in experimental mice with acute radiation syndrome (ARS). Forty mice were randomly divided into two equal groups of A receiving no BMSC transplantation and B receiving BMSCs. BMSCs were isolated from the bone marrow and cultured in DMEM media. Both groups were irradiated with 10 Gy (dose rate 0.28 Gy/ min) (60)CO during 35 minutes with a field size of 35×35 for all the body area. Twenty-four hours after γ irradiation, 150×10(3) cells of passage 5 in 150 µl medium were injected intravenously into the tail. Animals were euthanized one and two weeks after cell transplantation. They were evaluated histologically for any changes in bone marrow and intestinal tissues. The survival rate in mice were also determined. A significant increase for bone marrow cell count and survival rate were observed in group B in comparison to group A. Histological findings denoted to a healing in sample tissues. BMSCs could significantly reduce the side effects of ARS and increase the survival rate and healing in injured tissue. As such their transplantation may open a window in treatment of patients with ARS.

Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features.

PubMed

Bonciolini, Veronica; Bianchi, Beatrice; Del Bianco, Elena; Verdelli, Alice; Caproni, Marzia

2015-09-15

The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.

Effects of pristine polyvinyl chloride fragments on whole body histology and protease activity in silver barb Barbodes gonionotus fry.

PubMed

Romano, Nicholas; Ashikin, Munirah; Teh, Jun Chin; Syukri, Fadhil; Karami, Ali

2018-06-01

Silver barb Barbodes gonionotus fry were exposed to polyvinyl chloride (PVC) fragments at increasing concentrations of 0.2, 0.5 and 1.0 mg/L for 96 h, following which whole body histological evaluation and analysis of the digestive enzymes trypsin and chymotrypsin were performed. Whole body trypsin and chymotrypsin activities increased significantly in fish exposed to 0.5 and 1.0 mg/L PVC as compared those exposed to zero or 0.2 mg/L PVC. In fish exposed to all tested concentrations, PVCs were observed in both the proximal and distal intestine, and fish exposed to 0.5-1.0 and 1.0 mg/L PVC, respectively, and these particles were associated with localized thickening of the mucosal epithelium. No tissue damage was evident in any other internal organs or gills. This lack of damage may be attributed to the absence of contaminants associated with the PVC fragments and their relatively smooth surface. The increased whole body trypsin and chymotrypsin activities may indicate an attempt to enhance digestion to compensate for epithelial thickening of the intestine and/or to digest the plastics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adipocytes and intestinal epithelium dysfunctions linking obesity to inflammation induced by high glycemic index pellet-diet in Wistar rats.

PubMed

Luz, Anna Beatriz Santana; Dos Santos Figueredo, Júlia Braga; Salviano, Bianca Damásio Pereira Dantas; Aguiar, Ana Júlia Felipe Camelo; Pinheiro, Luiza Gabriella Soares Dantas; Krause, Matheus Felipe Dantas; da Silva Camillo, Christina; Ladd, Fernando Vagner Lobo; Bortolin, Raul Hernandes; Silbiger, Vivian Nogueira; Maciel, Bruna Leal Lima; de Araújo Morais, Ana Heloneida

2018-06-29

We investigated the inflammatory effect of a pellet-diet with high glycemic index and load (HGLI) on the histological organization of adipocytes, intestinal epithelium, and fat in liver and pancreas in adult male Wistar rats. Two groups ( n =10) received for 17 weeks: (1) HGLI diet or (2) Standard diet (Labina®). Histological analyses of adipose tissue, jejunum, liver, and pancreas were performed. Stereology analysis, visceral adiposity index, gene expression, and immunohistochemistry of tumor necrosis factor-α (TNF-α) in visceral adipose tissue and plasma TNF-α were also assessed. The HGLI diet-induced hypertrophy of adipocytes with adipocyte volume density equal to 97.0%, cross-sectional area of adipocytes equivalent to 1387 µm² and a total volume of adipocytes of 6.97 cm³ an elevation of 8%, 25%, and 58%, respectively. Furthermore, the HGLI diet increased liver and pancreatic fat deposition, altered and inflamed the intestinal epithelia, and increased TNF-α gene expression ( P =0.014) with a positive immunostaining in visceral adipose tissue and high plasma TNF-α in comparison with standard diet. The results suggest that this diet was able to generate changes commonly caused to solid diets with high fat or fructose-rich beverages. To the best of our knowledge, this is the first report in the literature concerning the properties of low-cost, sucrose-rich pellet-diet presenting high glycemic index and high glycemic load efficient on the development of obesity complications in Wistar rats that were subjected to diet-induced obesity. Therefore, the HGLI pellet-diet may be considered an effective tool to be used by the scientific community in experimental research. © 2018 The Author(s).

Histologic types of gastric cancer among migrants from the former Soviet Union and the general population in Germany: what kind of prevention do we need?

PubMed

Jaehn, Philipp; Holleczek, Bernd; Becher, Heiko; Winkler, Volker

2016-08-01

The incidence of gastric cancer (GC) is high among migrants from Eastern Europe and Asia, but a detailed picture of disease characteristics is missing. Our study examined the incidence of histologic types among resettlers from the former Soviet Union and the general population in Germany to draw conclusions on risk factors and possible prevention strategies. Between 1990 and 2009, all GC diagnoses among a cohort of 18 619 resettlers residing in the Saarland were identified in the Saarland Cancer Registry database. Age-standardized incidence rates (ASRs) of the entire Saarland population and standardized incidence ratios (SIRs) of resettlers compared with the Saarland population were calculated for types according to Laurén. In addition, ASRs and SIRs were modeled using Poisson's regression to investigate time trends. The ASR of intestinal GC in the Saarland population decreased over time, whereas the ASR of diffuse GC remained unchanged. Resettlers' incidence of intestinal GC was elevated among men [SIR: 3.04, 95% confidence interval (CI): 2.05-4.50] and women (SIR: 2.78, 95% CI: 1.61-4.79), whereas diffuse GC was elevated only among women (SIR: 1.98, 95% CI: 1.07-3.69). No time trends for SIRs could be observed in regression analysis. Different trends of diffuse GC incidence in Germany and the USA underline the importance of environmental risk factors. The continuously elevated risk of GC among male resettlers is probably associated with risk factors affecting exclusively the intestinal type such as a low intake of fruit and vegetables and heavy alcohol consumption. Future prevention programs for resettlers should include dietary measures.

Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats.

PubMed

Gan, Xiaoliang; Liu, Dezhao; Huang, Pinjie; Gao, Wanling; Chen, Xinzhi; Hei, Ziqing

2012-06-01

Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.

Detection and localisation of the abalone probiotic Vibrio midae SY9 and its extracellular protease, VmproA, within the digestive tract of the South African abalone, Haliotis midae.

PubMed

Huddy, Robert J; Coyne, Vernon E

2014-01-01

Probiotics have been widely reported to increase the growth rate of commercially important fish and shellfish by enhancing the digestion of ingested feed through the production of extracellular enzymes such as proteases and alginases. In order to investigate this further, the objective of this study was to localise the bacterial probiont Vibrio midae SY9 and one of the extracellular proteases it produces in the digestive tract of the South African abalone Haliotis midae. This was accomplished by inserting a promotorless gfp gene into the chromosome of the bacterium which was incorporated in an artificial, fishmeal-based abalone feed. In situ histological comparison of abalone fed either a basal diet or the basal diet supplemented with V. midae SY9::Tn10.52 using a cocktail of DNA probes to the gfp gene localised the probiont to the crop/stomach and intestinal regions of the H. midae digestive tract. Generally, the ingested probiotic bacterium occurred in association with feed and particulate matter within the crop/stomach and intestinal regions, as well as adhered to the wall of the crop/stomach. Histological immunohistochemical examination using polyclonal anti-VmproA antibodies localised an extracellular protease produced by V. midae SY9 to the H. midae crop/stomach and intestine where it appeared to be associated with feed and/or other particulate matter in the abalone gut. Thus the data suggests that V. midae SY9 colonises and/or adheres to the mucous lining of the abalone gut. Furthermore, the close association observed between the bacterium, its extracellular protease and ingested feed particles supports the theory that V. midae SY9 elevates in situ digestive enzyme levels and thus enhances feed digestion in farmed abalone.

Evaluation of immune response, microbiota, and blood markers after probiotic bacteria administration in obese mice induced by a high-fat diet.

PubMed

Núñez, Ivanna Novotny; Galdeano, Carolina Maldonado; de LeBlanc, Alejandra de Moreno; Perdigón, Gabriela

2014-01-01

Obesity is associated with alterations in intestinal microbiota and immunity. The aim of this study was to determine the effect of probiotic Lactobacillus casei CRL 431 administration on intestinal and humoral immune response, clinical parameters, and gut microbiota was evaluated using a high-fat diet to induce obesity in a mouse model. Adult mice received a conventional balanced diet or a high-fat diet supplemented with milk, milk fermented by Lactobacillus casei (FM), L. casei as suspension, or water over 60 d. Histology of liver and small intestine (SI), immunoglobulin A-positive cells and macrophages in SI, phagocytic activity of spleen and peritoneal macrophages, and humoral immune response to ovalbumin were studied. Clinical parameters in serum and gut microbiota were also analyzed. FM was the most effective supplement for decreasing body weight and clinical parameters in serum. The histology of liver and SI was also improved in obese mice given FM. These animals had increased numbers of immunoglobulin A-positive cells and macrophages in SI. The gut microbiota showed that obese mice given probiotics had increased Bacteroides and bifidobacteria. Administration of FM or L. casei as suspension enhanced the phagocytic activity of macrophages. The anti-ovalbumin specific immune response was not increased by any supplement assayed. Administration of probiotics to obese hosts improved the gut microbiota and the mucosal immunity altered by obesity, down-regulated some biochemical parameters in blood associated with metabolic syndrome, and decreased liver steatosis. These results demonstrate the potential use of probiotics in obese individuals to decrease the body weight and to improve the biochemical and immunologic parameters altered by obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

Histological study of the gastrointestinal tract in longfin yellowtail (Seriola rivoliana) larvae.

PubMed

Teles, Andressa; Salas-Leiva, Joan; Alvarez-González, Carlos Alfonso; Gisbert, Enric; Ibarra-Castro, Leonardo; Urbiola, Juan Carlos Pérez; Tovar-Ramírez, Dariel

2017-12-01

This work contributes basic knowledge on larval development of Seriola rivoliana. A histological study describes the development of the digestive tract and accessory glands in S. rivoliana larvae reared under laboratory conditions at 24 °C from hatching to 30 days post-hatching (DPH). At hatching (2.6 ± 0.12 mm), larvae had an undifferentiated digestive tract with a closed straight tube and a large yolk sac with an oil globule. The liver and pancreas were observed at 1 and 2 days, and the mouth and anus opened at day 2. Enriched rotifers were visible in their digestive tract. At the beginning of the pre-flexion stage, a mixed nutritional period was observed. At day 3, exogenous feeding began; the digestive tract became differentiated into the buccopharynx, esophagus, an undifferentiated stomach, and the intestines. Zymogen granules were visible in the exocrine pancreas. At day 4, supranuclear vacuoles were present in the posterior intestine, indicating the beginning of intracellular digestion. At day 5, goblet cells were present in the esophagus and became functional at day 7 in the esophagus and intestine. The buccopharynx goblet cells developed at day 15. The presence of gastric glands and differentiation of the stomach in the fundic, cardiac, and pyloric regions during the post-flexion stage occurred at day 20. This was the onset of the juvenile period and the beginning of weaning; however, a long co-feeding phase is recommended. Pyloric caeca were observed at day 30 (13.6 ± 1.6 mm). These results provide valuable information on S. rivoliana larvae biology and digestive physiology, which should be useful to improve cultivation techniques and identify ecological features involved in ontogeny.

Farnesoid X Receptor Agonist Treatment Alters Bile Acid Metabolism but Exacerbates Liver Damage in a Piglet Model of Short-Bowel Syndrome.

PubMed

Pereira-Fantini, Prue M; Lapthorne, Susan; Gahan, Cormac G M; Joyce, Susan A; Charles, Jenny; Fuller, Peter J; Bines, Julie E

2017-07-01

Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction. OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration. Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PubMed

Agudo, Antonio; Bonet, Catalina; Sala, Núria; Muñoz, Xavier; Aranda, Núria; Fonseca-Nunes, Ana; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Vineis, Paolo; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Grioni, Sara; Quirós, J Ramón; Molina, Esther; Navarro, Carmen; Barricarte, Aurelio; Chamosa, Saioa; Allen, Naomi E; Khaw, Kay-Tee; Bueno-de-Mesquita, H Bas; Siersema, Peter D; Numans, Mattijs E; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Kaaks, Rudof; Canzian, Federico; Boeing, Heiner; Meidtner, Karina; Johansson, Mattias; Sund, Malin; Manjer, Jonas; Overvad, Kim; Tjonneland, Anne; Lund, Eiliv; Weiderpass, Elisabete; Jenab, Mazda; Fedirko, Veronika; Offerhaus, G Johan A; Riboli, Elio; González, Carlos A; Jakszyn, Paula

2013-06-01

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

Royal Jelly and Its Dual Role in TNBS Colitis in Mice

PubMed Central

Manzo, Luis Paulo; de-Faria, Felipe Meira; Dunder, Ricardo José; Rabelo-Socca, Eduardo Augusto; Consonni, Silvio Roberto; de Almeida, Ana Cristina Alves; Souza-Brito, Alba Regina Monteiro; Luiz-Ferreira, Anderson

2015-01-01

Royal Jelly (RJ) is widely consumed in diets throughout the world due to its beneficial effects: antioxidant, antitumor and anti-inflammatory. We have investigated the role of RJ in the development of TNBS colitis in mice. Colitis was induced by a rectal instillation of TNBS at 0.1 mL per mouse. Intestine samples of the animals orally treated with RJ (100, 150, and 200 mg/kg) were collected for antioxidant assays (GSH and GSH-Px), proinflammatory protein quantification (COX-2 and NF-κB), and histological analyses. RJ 100 mg/kg maintained GSH levels and increased the activity of GSH-Px, downregulated key inflammatory mediators (COX-2 and NF-κB), and decreased the lesions caused by TNBS as shown by the histological analyses. In conclusion, RJ showed anti-inflammatory and antioxidant properties in experimental colitis, resulting in the amelioration of the macroscopic and histological analyses. These results corroborate with the RJ supplementation in diets. PMID:25821860

HISTOLOGIC, IMMUNOHISTOCHEMICAL, AND ELECTRON MICROSCOPIC CHARACTERIZATION OF A MALIGNANT IRIDOPHOROMA IN A DWARF BEARDED DRAGON (POGONA HENRYLAWSONI).

PubMed

de Brot, Simone; Sydler, Titus; Nufer, Lisbeth; Ruetten, Maja

2015-09-01

A dwarf bearded dragon (Pogona henrylawsoni) was presented with a white subcutaneous mandibular mass and multiple nodules in the oral mucosa, heart, liver, kidney, intestine, and visceral fat. Histologically, the tumor consisted of densely packed spindle-shaped cells with brow intracytoplasmic pigment that exhibited white-blue birefringence with polarized light. Immunohistochemical staining was negative for S-100 and weakly positive with melan A. Electron microscopic examination revealed cytoplasmic irregular and oblong empty spaces, laminated and often arranged into short stacks, compatible with reflecting platelet profiles typically seen in iridophores. However, in unstained ultrathin sections, electron-dense crystalline material was present, which filled the empty spaces described for stained sections before. Based on histology, immunohistochemistry, and biologic behavior, a malignant iridophoroma was diagnosed. To the authors' knowledge, iridophoromas in lizards have rarely been characterized by using electronic microscopy. Moreover, this is the first description of an iridophoroma in a dwarf bearded dragon.

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta)

PubMed Central

Liu, David X.; Gilbert, Margaret H.; Wang, Xiaolei; Didier, Peter J.; Veazey, Ronald S.

2014-01-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report. PMID:23104953

Scanning and transmission electron microscopy of the damage to small intestinal mucosa following X irradiation or hyperthermia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carr, K.E.; Hume, S.P.; Marigold, J.C.

Scanning and transmission electron microscopy (S.E.M. and T.E.M.) and resin histology have been used to investigate the effects on mouse small intestinal villi of heating at 43 degrees C for 20 minutes and of irradiation with 10 Gy X-rays. Damage after irradiation included conical villi and giant cells. Damage after heating included the production of conical and rudimentary villi and the stacking of enterocytes. Individual cells showed signs of abnormalities in their cell membranes, nuclei and cytoplasmic components. The differences in the response after irradiation and hyperthermia are linked to the fact that heating has a primary effect on villousmore » structure, whereas irradiation mainly affects the proliferative pool of crypt cells.« less

Histopathological changes caused by the metacestodes of Neogryporhynchus cheilancristrotus (Wedl, 1855) in the gut of the gibel carp, Carassius gibelio.

PubMed

Molnár, K

2005-01-01

Metacestodes of Neogryporhynchus cheilancristrotus (Wedl, 1855) were found in the gut of some gibel carp (Carassius gibelio) specimens from a Hungarian water reservoir. Location of metacestodes in the freshly opened gut was marked with disseminated, red-coloured, pinhead-sized nodules in the anterior part of the intestine. In histological sections, metacestodes were found in a hole inside the propria layer of the intestinal folds. The worms were in direct contact with the host tissue without being encapsulated as a result of host reaction. In some specimens with extruded rostellum the rostellar hooks were bored into the host tissue and suckers grabbed pieces of the surrounding connective tissue. Around the worms, congested capillaries and formation of macrophages were seen in the lysed connective tissue.

Disseminated Yersinia pseudotuberculosis infection in a paca (Cuniculus paca).

PubMed

Fogelson, Susan B; Yau, Wilson; Rissi, Daniel R

2015-03-01

A 2-yr-old paca (Cuniculus paca) was presented for necropsy with a history of sudden death. GrosS examination revealed multifocal, transmural, well-demarcated, white, soft nodules scattered along the length of the small intestine. The liver also had similar nodules associated with the capsular and cut surface. Histologic evaluation of several organs, including the intestine, liver, lung, kidney, adrenal gland, and lymph nodes, was consistent with disseminated yersiniosis. In addition, aerobic bacterial culture of liver and lung tissue yielded heavy growth of Yersinia pseudotuberculosis. Yersinia pseudotuberculosis is a Gram-negative, enteric pathogen that can cause disease in a variety of terrestrial species including humans. Although systemic infection has been observed in rodent species, to our knowledge this is the first report of disseminated Y pseudotuberculosis in a paca.

Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine.

PubMed

Bradford, Emily M; Vairamani, Kanimozhi; Shull, Gary E

2016-02-15

To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen

PubMed Central

Bellanova, G.; Valduga, P.; Costa, A.; Barbareschi, M.; De Carli, N.; Giannelli, G.; Di Sipio, A.; Prezzi, C.; Ciarleglio, F.A.; Beltempo, P.; Marcucci, S.; Giacomin, D.; Depretis, G.; Brolese, A.

2015-01-01

Introduction Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. Materials and methods A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel’s diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2 mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. Discussion The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. Conclusion Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery. PMID:26188982

3D stromal tissue equivalent affects intestinal epithelium morphogenesis in vitro.

PubMed

De Gregorio, Vincenza; Imparato, Giorgia; Urciuolo, Francesco; Netti, Paolo A

2018-04-01

Current in vitro models of human intestine commonly fail to mimic the complex intestinal functions and features required for drug development and disease research. Here, we deeply investigate the interaction existing between epithelium and the underneath stroma, and its role in the epithelium morphogenesis. We cultured human intestinal subepithelial myofibroblasts (ISEMFs) in two different 3D configurations: 3D-collagen gel equivalent (3D-CGE) and 3D cell-synthetized stromal equivalent (3D-CSSE). The 3D-CGEs were obtained by means of the traditional collagen-based cell technique and the 3D-CSSE were obtained by bottom-up tissue engineering strategy. The biophysical properties of both 3D models with regard to cell growth and composition (via histological analysis, immunofluorescence, and multiphoton imaging) were assessed. Then, human colorectal adenocarcinoma cell line (CaCo-2) was cultured on both the 3D constructs in order to produce the intestinal model. We identified higher levels of matrix-associated proteins from ISEMFs cultured in 3D-CSSE compared to 3D-CGE. Furthermore, multiphoton investigation revealed differences in the collagen network architecture in both models. At last, the more physiologically relevant stromal environment of the 3D-CSSE drove the CaCo-2 cell differentiation toward the four different type of intestinal epithelial cells (absorptive, mucus-secretory, enteroendocrine, and Paneth) phenotype and promotes, in contrast to the 3D-CGE, the production of the basement membrane. Taken together, these results highlight a fundamental role of the 3D stromal environment in addressing a correct epithelium morphogenesis as well as epithelial-stromal interface establishment. © 2017 Wiley Periodicals, Inc.

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

The effect of diet on ontogenic development of the digestive tract in juvenile reared long snout seahorse Hippocampus guttulatus.

PubMed

Palma, J; Bureau, D P; Andrade, J P

2014-06-01

Ontogenetic development of the digestive tract and associated organs in long snout seahorse Hippocampus guttulatus juveniles was morphologically and histologically examined from the time of release from the male's pouch until 72 h after the first meal. When released from the male's pouch, juvenile seahorses are small adult replicates. This means that unlike other teleost fish larvae, the first developmental phase has already taken place, and juveniles are morphologically prepared and able to feed on live prey immediately following parturition. At this stage, the buccopharynx, oesophagus, and intestine already appear to be fully developed. The intestine is divided into the midgut and hindgut by an intestinal valve, and intestinal villi are visible in the midgut. When fed with DHA-Selco(®) enriched Artemia, H. guttulatus juveniles developed a severe condition of overinflation of the gas bladder. The continuous overinflation of the gas bladder forced air into the gut (48 h after the first meal), resulting in overinflation of both the gut and the gas bladder (72 h after the first meal), and death occurred within 120 h after the first meal. When fed natural copepods, H. guttulatus juveniles continued a normal feeding activity with no signs of intestinal disorders, and the gas bladder and intestine maintained their normal shape. This is the first study to positively associate gas bladder overinflation of juvenile seahorses with nutritionally unbalanced diets, and not to gas supersaturation alone. It is therefore necessary to develop more adequate feed and/or enrichment products to improve the survival of juvenile seahorses in captivity.

Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis.

PubMed

Rigby, Rachael J; Carr, Jacquelyn; Orgel, Kelly; King, Stephanie L; Lund, P Kay; Dekaney, Christopher M

2016-09-02

Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.

Diagnostic yield of capsule endoscopy in refractory celiac disease.

PubMed

Barret, Maximilien; Malamut, Georgia; Rahmi, Gabriel; Samaha, Elia; Edery, Joël; Verkarre, Virginie; Macintyre, Elizabeth; Lenain, Emilie; Chatellier, Gilles; Cerf-Bensussan, Nadine; Cellier, Christophe

2012-10-01

Capsule endoscopy (CE) allows for the assessment of the small bowel in numerous intestinal diseases, including celiac disease (CD). The main advantage of CE is the complete visualization of the intestinal mucosal surface. The objective of this study was to investigate whether CE can predict the severity of CD and detect complications. We retrospectively studied the medical files of 9 patients with symptomatic CD, 11 patients with refractory celiac disease type I (RCDI) and 18 patients with refractory celiac disease type II (RCDII), and 45 patients without CD who were investigated both CE and upper endoscopy or enteroscopy. The type of CD was diagnosed on the basis of a centralized histological review, flow cytometry analysis of intraepithelial lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex polymerase chain reaction. A total of 47 CEs (10, 11, and 26 CEs in the symptomatic CD, RCDI, and RCDII groups, respectively) from the 38 celiac patients and 47 CEs from the 45 nonceliac patients were retrospectively reviewed. Villous atrophy, numerous, or distally located ulcers were more frequent in celiac patients than in controls. Among celiac patients, CE was of acceptable quality in 96% of cases and was complete in 62% of cases. The concordance of CE with histology for villous atrophy was better than that of optic endoscopy (κ coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on CE was associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). Three cases of overt lymphoma were detected by CE during the follow-up. CE findings have a satisfactory concordance with histology and nutritional status in patients with symptomatic or refractory CD. Moreover, CE may predict the type of RCD and allows for the early detection of overt lymphoma.

Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis.

PubMed

Wang, Jin; Xu, Lijuan; Shi, Ruihua; Huang, Xiayue; Li, Simon Wing Heng; Huang, Zuhu; Zhang, Guoxin

2011-01-01

Whether gastric atrophy (GA) and intestinal metaplasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-analysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradication. English-language articles in the medical literature containing information about the association between infection with H. pylori and gastric premalignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis. Twelve studies containing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histological alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00-0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09-0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (-0.12-0.16), p = 0.76, and for corpus IM, the pooled WMD was -0.02 (-0.05-0.02), p = 0.42. Our study shows that eradication of H. pylori results in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori-positive patients in those with GA in corpus. Copyright © 2011 S. Karger AG, Basel.

Mucosal Healing and the Risk of Ischemic Heart Disease or Atrial Fibrillation in Patients with Celiac Disease; A Population-Based Study

PubMed Central

Lebwohl, Benjamin; Emilsson, Louise; Fröbert, Ole; Einstein, Andrew J.; Green, Peter H. R.; Ludvigsson, Jonas F.

2015-01-01

Background Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF. Methods We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF. Results Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73–1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73–1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74–1.30). Conclusions In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events. PMID:25635403

Endoscopic intestinal bypass creation by using self-assembling magnets in a porcine model.

PubMed

Ryou, Marvin; Agoston, A Tony; Thompson, Christopher C

2016-04-01

A purely endoluminal method of GI bypass would be desirable for the treatment of obstruction, obesity, or metabolic syndrome. We have developed a technology based on miniature self-assembling magnets that create large-caliber anastomoses (Incisionless Anastomosis System [IAS]). The aim of this study was to evaluate procedural characteristics of IAS deployment and long-term anastomotic integrity and patency. We performed a 3-month survival study of Yorkshire pigs (5 interventions, 3 controls). Intervention pigs underwent simultaneous enteroscopy/colonoscopy performed with the animals under intravenous sedation. The IAS magnets were deployed and coupled with reciprocal magnets under fluoroscopy. Every 3 to 6 days pigs underwent endoscopy until jejunocolonic anastomosis (dual-path bypass) creation and magnet expulsion. Necropsies and histological evaluation were performed. The primary endpoints were technical success; secondary endpoints of anastomosis integrity, patency, and histological characteristics were weight trends. Under intravenous sedation, endoscopic bypass creation by using IAS magnets was successfully performed in 5 of 5 pigs (100%). Given porcine anatomy, the easiest dual-path bypass to create was between the proximal jejunum and colon. The mean procedure time was 14.7 minutes. Patent, leak-free anastomoses formed by day 4. All IAS magnets were expelled by day 12. All anastomoses were fully patent at 3 months with a mean diameter of 3.5 cm. The mean 3-month weight was 45 kg in bypass pigs and 78 kg in controls (P = .01). At necropsy, adhesions were absent. Histology showed full re-epithelialization across the anastomosis without fibrosis or inflammation. Large-caliber, leak-free, foreign body-free endoscopic intestinal bypass by using IAS magnets can be safely and rapidly performed in the porcine by model using only intravenous sedation. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells.

PubMed

Bribi, Noureddine; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Utrilla, María Pilar; Del Mar Contreras, María; Maiza, Fadila; Segura-Carretero, Antonio; Rodriguez-Cabezas, Maria Elena; Gálvez, Julio

2016-08-15

Fumaria capreolata L. (Papaveraceae) is a botanical drug used in North Africa for its gastro-intestinal and anti-inflammatory properties. It is characterized for the presence of several alkaloids that could be responsible for some of its effects, including an immunomodulatory activity. To test in vivo the intestinal anti-inflammatory properties of the total alkaloid fraction extracted from the aerial parts of F. capreolata (AFC), and to evaluate its effects on an intestinal epithelial cell line. AFC was chemically characterized by liquid chromatography coupled to diode array detection and high resolution mass spectrometry. Different doses of AFC (25, 50 and 100mg/kg) were assayed in the DNBS model of experimental colitis in mice, and the colonic damage was evaluated both histologically and biochemically. In addition, in vitro experiments were performed with this alkaloid fraction on the mouse intestinal epithelial cell line CMT93 stimulated with LPS. The chemical analysis of AFC revealed the presence of 23 alkaloids, being the most abundants stylopine, protopine and coptisine. Oral administration of AFC produced a significant inhibition of the release and the expression of IL-6 and TNF-α in the colonic tissue. It also suppressed in vivo the transcription of other pro-inflammatory mediators such as IL-1β, iNOS, IL-12 and IL-17. Furthermore, AFC showed an immunomodulatory effect in vitro since it was able to inhibit the mRNA expression of IL-6, TNF-α and ICAM-1. Moreover, the beneficial effect of AFC in the colitic mice could also be associated with the normalization of the expression of MUC-2 and ZO-1, which are important for the intestinal epithelial integrity. The present study suggests that AFC, containing 1.3% of stylopine and 0.9% of protopine, significantly exerted intestinal anti-inflammatory effects in an experimental model of mouse colitis. This fact could be related to a modulation of the intestinal immune response and a restoration of the intestinal epithelial function. Copyright © 2016 Elsevier GmbH. All rights reserved.

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction

PubMed Central

Li, Yu-Meng; Wang, Hai-Bin; Zheng, Jin-Guang; Bai, Xiao-Dong; Zhao, Zeng-Kai; Li, Jing-Yuan; Hu, Sen

2015-01-01

AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05). CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction. PMID:26478676

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.

PubMed

Li, Yu-Meng; Wang, Hai-Bin; Zheng, Jin-Guang; Bai, Xiao-Dong; Zhao, Zeng-Kai; Li, Jing-Yuan; Hu, Sen

2015-10-14

To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05). DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.

Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters.

PubMed

Lee, C Y

2015-04-01

This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%. Exposure to both stress and HFD caused a further increase in corticosterone to 41%, while decreasing plasma adiponectin level. Restraint stress altered intestinal expression of SLC5A1, SLC2A2 and NPC1L1. These changes were enhanced in SHF rats. Adenosine was found to alleviate HFD-induced increase in glucose and insulin levels, suppress elevation of corticosterone in S rats and improve the altered nutrient transporters expression profiles. It also prevented upregulation of TNF-α in the intestine of SHF rats. In summary, a combination of stress and HFD exaggerated stress- and HFD-induced pathophysiological changes in the intestine, and biochemical parameters related to obesity. Adenosine attenuated the elevation of corticosterone and altered expression of SLC5A1, NPC1L1 and TNF-α. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.

PubMed

Cresci, Gail A; Glueck, Bryan; McMullen, Megan R; Xin, Wei; Allende, Daniella; Nagy, Laura E

2017-09-01

Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll-like receptors, and tumor necrosis factor-alpha were assessed. Caco-2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic toll-like receptor mRNA expression and tumor necrosis factor-alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice. Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Probiotic administration modifies the milk fatty acid profile, intestinal morphology, and intestinal fatty acid profile of goats.

PubMed

Apás, A L; Arena, M E; Colombo, S; González, S N

2015-01-01

The effect of a mixture of potentially probiotic bacteria (MPPB; Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39, and Bifidobacterium bifidum strains) on the milk fatty acid (FA) profile, with emphasis on cis-9,trans-11 conjugated linoleic acid (CLA) in the middle stage of goat lactation, was determined. In addition, the effects of MPPB feeding on the FA profile in intestinal content and intestinal morphology in weaned goats were analyzed. The probiotic supplement was able to modify FA composition of milk and intestinal content. The unsaturated FA concentrations in milk (g of FA/L of milk) increased from 4.49 to 7.86 for oleic (18:1), from 0.70 to 1.39 for linoleic (18:2), from 0.063 to 0.187 for linolenic (18:3) acid, and from 0.093 to 0.232 for CLA. The atherogenicity index diminished 2-fold after MPPB ingestion. In the intestinal content of the weaned goats, no significant difference in saturated FA concentration compared with the control was observed. However, oleic acid, linolenic acid, CLA, and docosahexaenoic acid concentrations increased by 81, 23, 344, and 74%, respectively, after probiotic consumption. The ruminal production of CLA was increased by the MPPB. However, bacterial strains of MPPB were unable to produce CLA in culture media. By histological techniques, it was observed that the treated group had intestinally more conserved morphological structures than the control group. The results obtained in this study indicate that the MPPB administration in lactating and weaned goats allows for the production of milk with improved concentrations of beneficial compounds, and also produces a protective effect in the goat intestine. The results obtained in this study reinforce the strategy of probiotics application to enhance goat health with the production of milk with higher concentrations of polyunsaturated FA. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide.

PubMed

Melo, Maria Luisa P; Brito, Gerly A C; Soares, Rudy C; Carvalho, Sarah B L M; Silva, Johan V; Soares, Pedro M G; Vale, Mariana L; Souza, Marcellus H L P; Cunha, Fernando Q; Ribeiro, Ronaldo A

2008-04-01

Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA. CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients.

PubMed

Fullerton, Brenna S; Sparks, Eric A; Hall, Amber M; Duggan, Christopher; Jaksic, Tom; Modi, Biren P

2016-01-01

Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy-proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Regression of gastric intestinal metaplasia after the eradication of Helicobacter pylori infection in a hospital in Mexico.

PubMed

Sánchez Cuén, Jaime Alberto; Irineo Cabrales, Ana Bertha; Bernal Magaña, Gregorio; Peraza Garay, Felipe

2016-12-01

Intestinal metaplasia is a precursor lesion of gastric cancer. Infection by Helicobacter pylori is the principal cause of metaplasia. While evidence of the regression of metaplasia after treatment to eradicate this infection has been demonstrated, controversy remains with regard to this subject. The objective of this study was to determine the frequency of the regression of gastric intestinal metaplasia one year after the eradication of Helicobacter pylori. A prospective longitudinal designed study was carried out. The population studied in this research consisted of patients attending the Endoscopy Unit to undergo an upper endoscopy, in whom various symptoms indicated intestinal metaplasia associated with Helicobacter pylori, and who received standard empiric triple therapy to eradicate the bacteria. An upper endoscopy was performed in which four gastric biopsy samples were taken (two from the antrum and two from the body) before and after the eradicating treatment, with the endoscopic and histological findings studied after one year of monitoring. The statistical analysis was conducted using the Fisher's exact test and the McNemar's test. Forty-six patients were studied, of whom 20 (43.5%) were men and 26 (56.5%) were women, with an average age of 58.9 (DE 11.2). Intestinal metaplasia was found in 46 (100%) patients before treatment and in 21 (45.7%) patients post-eradication. Complete intestinal metaplasia (type I) was found in 35 patients (76.1%) before treatment and in 11 (23.9%) patients post-eradication (p = 0.000), while incomplete intestinal metaplasia (type II) was found in 10 (21.7%) patients before treatment and in 10 (21.7%) patients post-eradication. Non-atrophic chronic gastritis was found in 35 (76.1%) patients before treatment and in 32 (69.6%) patients post-eradication. In this study, gastric intestinal metaplasia associated with Helicobacter pylori infection showed a regression of 54.3% one year after the eradication of this microorganism. This treatment could modify the natural history of the development of gastric cancer.

RNA-Seq Reveals Dynamic Changes of Gene Expression in Key Stages of Intestine Regeneration in the Sea Cucumber Apostichopus japonicas

PubMed Central

Sun, Lina; Yang, Hongsheng; Chen, Muyan; Ma, Deyou; Lin, Chenggang

2013-01-01

Background Sea cucumbers (Holothuroidea; Echinodermata) have the capacity to regenerate lost tissues and organs. Although the histological and cytological aspects of intestine regeneration have been extensively studied, little is known of the genetic mechanisms involved. There has, however, been a renewed effort to develop a database of Expressed Sequence Tags (ESTs) in Apostichopus japonicus, an economically-important species that occurs in China. This is important for studies on genetic breeding, molecular markers and special physiological phenomena. We have also constructed a library of ESTs obtained from the regenerative body wall and intestine of A. japonicus. The database has increased to ∼30000 ESTs. Results We used RNA-Seq to determine gene expression profiles associated with intestinal regeneration in A. japonicus at 3, 7, 14 and 21 days post evisceration (dpe). This was compared to profiles obtained from a normally-functioning intestine. Approximately 5 million (M) reads were sequenced in every library. Over 2400 up-regulated genes (>10%) and over 1000 down-regulated genes (∼5%) were observed at 3 and 7dpe (log2Ratio≥1, FDR≤0.001). Specific “Go terms” revealed that the DEGs (Differentially Expressed Genes) performed an important function at every regeneration stage. Besides some expected pathways (for example, Ribosome and Spliceosome pathway term), the “Notch signaling pathway,” the “ECM-receptor interaction” and the “Cytokine-cytokine receptor interaction” were significantly enriched. We also investigated the expression profiles of developmental genes, ECM-associated genes and Cytoskeletal genes. Twenty of the most important differentially expressed genes (DEGs) were verified by Real-time PCR, which resulted in a trend concordance of almost 100% between the two techniques. Conclusion Our studies demonstrated dynamic changes in global gene expression during intestine regeneration and presented a series of candidate genes and enriched pathways that contribute to intestine regeneration in sea cucumbers. This provides a foundation for future studies on the genetics/molecular mechanisms associated with intestine regeneration. PMID:23936330

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410

Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Junru; Boerma, Marjan; Kulkarni, Ashwini

2010-07-15

Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 daysmore » after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.« less

Porcine Intestinal Mast Cells. Evaluation of Different Fixatives for Histochemical Staining Techniques Considering Tissue Shrinkage

PubMed Central

Rieger, J.; Twardziok, S.; Huenigen, H.; Hirschberg, R.M.; Plendl, J.

2013-01-01

Staining of mast cells (MCs), including porcine ones, is critically dependent upon the fixation and staining technique. In the pig, mucosal and submucosal MCs do not stain or stain only faintly after formalin fixation. Some fixation methods are particularly recommended for MC staining, for example the fixation with Carnoy or lead salts. Zinc salt fixation (ZSF) has been reported to work excellently for the preservation of fixation-sensitive antigens. The aim of this study was to establish a reliable histological method for counting of MCs in the porcine intestinum. For this purpose, different tissue fixation and staining methods that also allow potential subsequent immunohistochemical investigations were evaluated in the porcine mucosa, as well as submucosa of small and large intestine. Tissues were fixed in Carnoy, lead acetate, lead nitrate, Zamboni and ZSF and stained subsequently with either polychromatic methylene blue, alcian blue or toluidine blue. For the first time our study reveals that ZSF, a heavy metal fixative, preserves metachromatic staining of porcine MCs. Zamboni fixation was not suitable for histochemical visualization of MCs in the pig intestine. All other tested fixatives were suitable. Alcian blue and toluidine blue co-stained intestinal goblet cells which made a prima facie identification of MCs difficult. The polychromatic methylene blue proved to be the optimal staining. In order to compare MC counting results of the different fixation methods, tissue shrinkage was taken into account. As even the same fixation caused shrinkagedifferences between tissue from small and large intestine, different factors for each single fixation and intestinal localization had to be calculated. Tissue shrinkage varied between 19% and 57%, the highest tissue shrinkage was found after fixation with ZSF in the large intestine, the lowest one in the small intestine after lead acetate fixation. Our study emphasizes that MC counting results from data using different fixation techniques can only be compared if the respective studyimmanent shrinkage factor has been determined and quantification results are adjusted accordingly. PMID:24085270

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".

Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

PubMed

Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

2013-01-01

Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

Regulatory Efficacy of Brown Seaweed Lessonia nigrescens Extract on the Gene Expression Profile and Intestinal Microflora in Type 2 Diabetic Mice.

PubMed

Zhao, Chao; Yang, Chengfeng; Chen, Mingjun; Lv, Xucong; Liu, Bin; Yi, Lunzhao; Cornara, Laura; Wei, Ming-Chi; Yang, Yu-Chiao; Tundis, Rosa; Xiao, Jianbo

2018-02-01

In this study, the antidiabetic activity of Lessonia nigrescens ethanolic extract (LNE) is investigated in streptozotocin (SZT)-induced type 2 diabetic mice fed with a high-sucrose/high-fat diet. Ultra high performance liquid chromatography coupled with photo-DAD and electospray ionization-mass spectrometry (ESI-MS) is employed to analyze the major compounds in LNE. The components of the intestinal microflora in type 2 diabetic mice are analyzed by high-throughput next-generation 16S rRNA gene sequencing. Fasting blood glucose levels in diabetic mice are significantly decreased after LNE administration. The histology reveals that LNE could protect the cellular architecture of liver and kidney. LNE treatment significantly increases Bacteroidetes and decreases Firmicutes populations in intestinal microflora. Specifically, It could selectively enrich the amounts of beneficial bacteria, Barnesiella, as well as reduce the abundances of Clostridium and Alistipes. The increased gene and protein expression levels of phosphatidylinositol 3-kinase (PI3K) in the liver are observed in LNE treatment groups, while the expressions of c-Jun N-terminal kinase (JNK) are significantly downregulated. The above findings suggest that LNE could be considered as a functional food for reducing blood glucose and regulating intestinal microflora. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dietary betaine affect duodenal histology of broilers challenged with a mixed coccidial infection.

PubMed

Hamidi, H; Pourreza, J; Rahimi, H

2009-02-01

The purpose of this research was to investigate effect of dietary betaine on intestinal morphology after an experimental coccidiosis. Hence a total of 189 male and female broiler chicks were randomly assigned to 9 floor cages. Chicks were fed a basal diet supplemented with 0, 0.6 or 1.2 g kg(-1) betaine. All birds were inoculated orally with Eimeria oocysts on day 28. Duodenal morphology parameters and lesions were scored by microscopic observation on intestine samples which were taken at day 42 of age. Adding 1.2 g kg(-1) betaine to diet diminished intestinal lesions (p < 0.05). Dietary supplementation with 0.6 or 1.2 g kg(-1) betaine significantly (p < 0.01) increased intraepithelial lymphocytes as well. Level of additive betaine had no effect on the ratio of villus height/crypt depth or villus surface area. Lamina propria of duodenum became thicker in the intestine of chickens which received more supplemental betaine via their diet. In conclusion, since the number of intraepithelial lymphocytes and thickness of lamina propria represent the condition of gut immune response, it seems that dietary betaine may immunomodulate the gastrointestinal tract of broilers. In addition, betaine effect on villus morphology measured later in life differed from what had been measured already earlier in life of the chicks.

Effects of Gliadin consumption on the Intestinal Microbiota and Metabolic Homeostasis in Mice Fed a High-fat Diet

PubMed Central

Zhang, Li; Andersen, Daniel; Roager, Henrik Munch; Bahl, Martin Iain; Hansen, Camilla Hartmann Friis; Danneskiold-Samsøe, Niels Banhos; Kristiansen, Karsten; Radulescu, Ilinca Daria; Sina, Christian; Frandsen, Henrik Lauritz; Hansen, Axel Kornerup; Brix, Susanne; Hellgren, Lars I.; Licht, Tine Rask

2017-01-01

Dietary gluten causes severe disorders like celiac disease in gluten-intolerant humans. However, currently understanding of its impact in tolerant individuals is limited. Our objective was to test whether gliadin, one of the detrimental parts of gluten, would impact the metabolic effects of an obesogenic diet. Mice were fed either a defined high-fat diet (HFD) containing 4% gliadin (n = 20), or a gliadin-free, isocaloric HFD (n = 20) for 23 weeks. Combined analysis of several parameters including insulin resistance, histology of liver and adipose tissue, intestinal microbiota in three gut compartments, gut barrier function, gene expression, urinary metabolites and immune profiles in intestinal, lymphoid, liver and adipose tissues was performed. Mice fed the gliadin-containing HFD displayed higher glycated hemoglobin and higher insulin resistance as evaluated by the homeostasis model assessment, more hepatic lipid accumulation and smaller adipocytes than mice fed the gliadin-free HFD. This was accompanied by alterations in the composition and activity of the gut microbiota, gut barrier function, urine metabolome, and immune phenotypes within liver and adipose tissue. Our results reveal that gliadin disturbs the intestinal environment and affects metabolic homeostasis in obese mice, suggesting a detrimental effect of gluten intake in gluten-tolerant subjects consuming a high-fat diet. PMID:28300220

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy

PubMed Central

Palestro, Giorgio; Pellicano, Rinaldo; Fronda, Gian Ruggero; Valente, Guido; Giuli, Marco De; Soldati, Tito; Pugliese, Agostino; Taraglio, Stefano; Garino, Mauro; Campra, Donata; Cutufia, Miguel Angel; Margaria, Elena; Spinzi, Giancarlo; Ferrara, Aldo; Marenco, Giorgio; Rizzetto, Mario; Ponzetto, Antonio

2005-01-01

AIM: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC). METHODS: Samples from 317 (184 males, 133 females, mean age 69±3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3±4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic “gold standard”. An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG). RESULTS: Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III (type III vs others, P = 0.4). CONCLUSION: This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor. PMID:16437659

Environmental Enteric Dysfunction in Children.

PubMed

Syed, Sana; Ali, Asad; Duggan, Christopher

2016-07-01

Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

Enterocolic lymphocytic phlebitis: clinicopathologic features and review of the literature.

PubMed

Ngo, Nyethane; Chang, Fuju

2007-07-01

Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

PubMed Central

Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

2014-01-01

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

Adenine Inhibits TNF-α Signaling in Intestinal Epithelial Cells and Reduces Mucosal Inflammation in a Dextran Sodium Sulfate-Induced Colitis Mouse Model.

PubMed

Fukuda, Toshihiko; Majumder, Kaustav; Zhang, Hua; Turner, Patricia V; Matsui, Toshiro; Mine, Yoshinori

2016-06-01

Adenine (6-amino-6H-purine), found in molokheiya (Corchorus olitorius L.), has exerted vasorelaxation effects in the thoracic aorta. However, the mode of action of the anti-inflammatory effect of adenine is unclear. Thus, we investigated to clarify the effect of adenine on chronic inflammation of the gastrointestinal tract. In intestinal epithelial cells, adenine significantly inhibited tumor necrosis factor-α-induced interleukin-8 secretion. The inhibition of adenine was abolished under the treatment of inhibitors of adenyl cyclase (AC) and protein kinase A (PKA), indicating the effect of adenine was mediated through the AC/PKA pathway. Adenine (5, 10, and 50 mg/kg BW/day) was administered orally for 14 days to female BALB/c mice, and then 5% dextran sodium sulfate (DSS) was given to induce colitis. Adenine (5 mg/kg BW/day) significantly prevented DSS-induced colon shortening, expression of pro-inflammatory cytokines, and histological damage in the colon. These results suggest that adenine can be a promising nutraceutical for the prevention of intestinal inflammation.

"Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

PubMed

Chung, C-S; Lee, T-H; Chiu, C-T; Chen, Y

2017-12-01

Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Rehabilitative therapy of short bowel syndrome: experimental study and clinical trial.

PubMed

Li, N; Zhu, W; Guo, F; Ren, J; Li, Y; Wang, X; Li, J

2000-08-01

To investigate the effect of growth hormone on proliferative activity of the residual small intestinal mucosa after massive small intestinal resection and to evaluate the clinical efficacy of bowel rehabilitative therapy for short bowel syndrome. Small intestinal mucosa proliferative activity were compared in rats from control group (sham operation), short bowel group (80% small bowel resection) and growth hormone treatment group (80% small bowel resection + growth hormone 1 U x kg(-1) x d(-1) for 28 days) with the aid of histology image analysis, flow cytometric assay, immunohistochemistry analysis and RT-PCR assay. The nutritional status, D-xylose absorption and stool nitrogen output were observed in 9 consecutive parenteral nutrition dependent patients with short bowel syndrome after intestinal rehabilitative therapy (growth hormone 8 - 12 U x kg(-1) x d(-1) im + glutamine 0.6 g x kg(-1) x d(-1) iv + special diet) for 21 continuous days. Growth hormone administration significantly increased rat small intestinal mucosal villous height, mucosal thickness, proliferative index, and the expression of proliferating cell nuclear antigen and c-jun mRNA. Rehabilitative therapy increased the body weight, serum total protein and album in concentrations in patients. Their D-xylose absorption indices increased and fecal nitrogen losses decreased. Follow-up data showed that 6 of the 9 patients sustained on enteral nutrition. Growth hormone enhances the proliferative activity of the mucosal epithelium and bowel rehabilitative therapy may benefit the patients with short bowel syndrome.

Safety and Protective Effectiveness of Two Strains of Lactobacillus with Probiotic Features in an Experimental Model of Salmonellosis

PubMed Central

Steinberg, Raphael S.; Silva, Lilian C. S.; Souza, Tássia C.; Lima, Maurício T.; de Oliveira, Nayara L. G.; Vieira, Leda Q.; Arantes, Rosa M. E.; Miyoshi, Anderson; Nicoli, Jacques R.; Neumann, Elisabeth; Nunes, Álvaro C.

2014-01-01

Two strains of Lactobacillus, previously isolated from bovine faeces and tested in vitro for properties desired in probiotics, were evaluated for their in vivo effectiveness in protecting against experimental salmonellosis. L. salivarius L38 and L. acidophilus L36 previously demonstrated the ability to successfully colonize the gastrointestinal tract of germ-free mice and stimulate the immune system associated with the intestinal mucosa. L38- or L36-feeding showed no detrimental effect on the general health indicators and did not induce changes in normal architecture of liver and small intestine, indicating that the use of these strains is apparently safe. In control animals fed L38 strain, several cytokines had augmented mRNA levels that can be associated with a homeostatic state of intestinal mucosa, while L36 had less diverse regulation. IgA production and secretion in the intestinal lumen induced by infection was abrogated by pretreating with both lactobacilli. In addition, liver and small intestine histological scores and, translocation of Salmonella cells to liver and spleen, indicated that these strains did not confer protection against the infection. So, the IL-12:IL-18➔IFN-γ axis, essential for an effective immune response against Salmonella, was not favored with L38 or L36 strains. However, increased expression of IL-10 in different portions of the gastrointestinal tract of L38-fed animals is indicative of anti-inflammatory effect to be explored furthermore. PMID:25162711

Safety and protective effectiveness of two strains of Lactobacillus with probiotic features in an experimental model of salmonellosis.

PubMed

Steinberg, Raphael S; Silva, Lilian C S; Souza, Tássia C; Lima, Maurício T; de Oliveira, Nayara L G; Vieira, Leda Q; Arantes, Rosa M E; Miyoshi, Anderson; Nicoli, Jacques R; Neumann, Elisabeth; Nunes, Alvaro C

2014-08-26

Two strains of Lactobacillus, previously isolated from bovine faeces and tested in vitro for properties desired in probiotics, were evaluated for their in vivo effectiveness in protecting against experimental salmonellosis. L. salivarius L38 and L. acidophilus L36 previously demonstrated the ability to successfully colonize the gastrointestinal tract of germ-free mice and stimulate the immune system associated with the intestinal mucosa. L38- or L36-feeding showed no detrimental effect on the general health indicators and did not induce changes in normal architecture of liver and small intestine, indicating that the use of these strains is apparently safe. In control animals fed L38 strain, several cytokines had augmented mRNA levels that can be associated with a homeostatic state of intestinal mucosa, while L36 had less diverse regulation. IgA production and secretion in the intestinal lumen induced by infection was abrogated by pretreating with both lactobacilli. In addition, liver and small intestine histological scores and, translocation of Salmonella cells to liver and spleen, indicated that these strains did not confer protection against the infection. So, the IL-12:IL-18àIFN-g axis, essential for an effective immune response against Salmonella, was not favored with L38 or L36 strains. However, increased expression of IL-10 in different portions of the gastrointestinal tract of L38-fed animals is indicative of anti-inflammatory effect to be explored furthermore.

Dietary microbial phytase exerts mixed effects on the gut health of tilapia: a possible reason for the null effect on growth promotion.

PubMed

Hu, Jun; Ran, Chao; He, Suxu; Cao, Yanan; Yao, Bin; Ye, Yuantu; Zhang, Xuezhen; Zhou, Zhigang

2016-06-01

The present study evaluated the effects of dietary microbial phytase on the growth and gut health of hybrid tilapia (Oreochromis niloticus ♀×Oreochromis aureus ♂), focusing on the effect on intestinal histology, adhesive microbiota and expression of immune-related cytokine genes. Tilapia were fed either control diet or diet supplemented with microbial phytase (1000 U/kg). Each diet was randomly assigned to four groups of fish reared in cages (3×3×2 m). After 12 weeks of feeding, weight gain and feed conversion ratio of tilapia were not significantly improved by dietary microbial phytase supplementation. However, significantly higher level of P content in the scales, tighter and more regular intestinal mucosa folds were observed in the microbial phytase group and the microvilli density was significantly increased. The adhesive gut bacterial communities were strikingly altered by microbial phytase supplementation (0·41

Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans

PubMed Central

Pereira, Dora I.A.; Bruggraber, Sylvaine F.A.; Faria, Nuno; Poots, Lynsey K.; Tagmount, Mani A.; Aslam, Mohamad F.; Frazer, David M.; Vulpe, Chris D.; Anderson, Gregory J.; Powell, Jonathan J.

2014-01-01

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P < 0.0001) and direct in vitro cellular uptake (P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia. From the Clinical Editor This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition. PMID:24983890

MR enterography-histology comparison in resected pediatric small bowel Crohn disease strictures: can imaging predict fibrosis?

PubMed

Barkmeier, Daniel T; Dillman, Jonathan R; Al-Hawary, Mahmoud; Heider, Amer; Davenport, Matthew S; Smith, Ethan A; Adler, Jeremy

2016-04-01

Crohn disease is a chronic inflammatory condition that can lead to intestinal strictures. The presence of fibrosis within strictures alters optimal management but is not reliably detected by current imaging methods. To correlate the MRI features of surgically resected small-bowel strictures in pediatric Crohn disease with histological inflammation and fibrosis scoring. We included children with Crohn disease who had symptomatic small-bowel strictures requiring surgical resection and had preoperative MR enterography (MRE) within 3 months of surgery (n = 20). Two blinded radiologists reviewed MRE examinations to document stricture-related findings. A pediatric pathologist scored stricture histological specimens for fibrosis (0-4) and inflammation (0-4). MRE findings were correlated with histological data using Spearman correlation (ρ) and exact logistic regression analysis. There was significant positive correlation between histological bowel wall fibrosis and inflammation in resected strictures (ρ = 0.55; P = 0.01). Confluent transmural histological fibrosis was associated with pre-stricture upstream small-bowel dilatation >3 cm at univariate (odds ratio [OR] = 51.7; 95% confidence interval [CI]: 7.6- > 999.9; P = 0.0002) and multivariate (OR = 43.4; 95% CI: 6.1- > 999.9; P = 0.0006, adjusted for age) analysis. The degree of bowel wall T2-weighted signal intensity failed to correlate with histological bowel wall fibrosis or inflammation (P-values >0.05). There were significant negative correlations between histological fibrosis score and patient age at resection (ρ = -0.48, P = 0.03), and time from diagnosis to surgery (ρ = -0.73, P = 0.0002). Histological fibrosis and inflammation co-exist in symptomatic pediatric Crohn disease small-bowel strictures and are positively correlated. Pre-stenotic upstream small-bowel dilatation greater than 3 cm is significantly associated with confluent transmural fibrosis.

Chir99021 and Valproic acid reduce the proliferative advantage of Apc mutant cells.

PubMed

Langlands, Alistair J; Carroll, Thomas D; Chen, Yu; Näthke, Inke

2018-02-15

More than 90% of colorectal cancers carry mutations in Apc that drive tumourigenesis. A 'just-right' signalling model proposes that Apc mutations stimulate optimal, but not excessive Wnt signalling, resulting in a growth advantage of Apc mutant over wild-type cells. Reversal of this growth advantage constitutes a potential therapeutic approach. We utilised intestinal organoids to compare the growth of Apc mutant and wild-type cells. Organoids derived from Apc Min/+ mice recapitulate stages of intestinal polyposis in culture. They eventually form spherical cysts that reflect the competitive growth advantage of cells that have undergone loss of heterozygosity (LOH). We discovered that this emergence of cysts was inhibited by Chiron99021 and Valproic acid, which potentiates Wnt signalling. Chiron99021 and Valproic acid restrict the growth advantage of Apc mutant cells while stimulating that of wild-type cells, suggesting that excessive Wnt signalling reduces the relative fitness of Apc mutant cells. As a proof of concept, we demonstrated that Chiron99021-treated Apc mutant organoids were rendered susceptible to TSA-induced apoptosis, while wild-type cells were protected.

Organisation of autonomic nervous structures in the small intestine of chinchilla (Chinchilla laniger, Molina).

PubMed

Nowak, E

2014-08-01

Using histochemical, histological and immunocytochemical methods, organisation of the autonomic nerve structures in small intestine of chinchilla was investigated. Myenteric plexus was localised between circular and longitudinal layers of the smooth muscles. Forming network nodes, the small autonomic, cholinergic ganglia were linked with the bundles of nerve fibres. Adrenergic structures were visible as specific varicose, rosary-like fibres forming bundles of parallel fibres connecting network nodes. Structures of the submucosal plexus formed a finer network than those of the myenteric plexus. Moreover, in 'whole-mount' specimens, fibres forming thick perivascular plexuses were also observed. Immunocytochemical studies confirmed the cholinergic and adrenergic character of the investigated structures. VAChT-positive neurones were found only in myenteric plexus, and numerous VAChT-positive and DBH-positive fibres were found in both plexuses. © 2013 Blackwell Verlag GmbH.

Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility.

PubMed

Nassif, A; Longo, W E; Sexe, R; Stratton, M; Standeven, J; Vernava, A M; Kaminski, D L

1995-01-01

We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10(-8) M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E(2) and thromboxane B(2). Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation.

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Kamran A.; Caudell, Jimmy J.; El-Haddad, Ghassan

Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRTmore » was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.« less

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

PubMed

Rostami-Nejad, Mohammad; Hejazi, Seyed Hossein; Peña, Amado Salvador; Asadzadeh-Aghdaei, Hamid; Rostami, Kamran; Volta, Umberto; Zali, Mohammad Reza

2018-05-18

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Micro-structurally detailed model of a therapeutic hydrogel injectate in a rat biventricular cardiac geometry for computational simulations

PubMed Central

Sirry, Mazin S.; Davies, Neil H.; Kadner, Karen; Dubuis, Laura; Saleh, Muhammad G.; Meintjes, Ernesta M.; Spottiswoode, Bruce S.; Zilla, Peter; Franz, Thomas

2013-01-01

Biomaterial injection based therapies have showed cautious success in restoration of cardiac function and prevention of adverse remodelling into heart failure after myocardial infarction (MI). However, the underlying mechanisms are not well understood. Computational studies utilised simplified representations of the therapeutic myocardial injectates. Wistar rats underwent experimental infarction followed by immediate injection of polyethylene glycol hydrogel in the infarct region. Hearts were explanted, cryo-sectioned and the region with the injectate histologically analysed. Histological micrographs were used to reconstruct the dispersed hydrogel injectate. Cardiac magnetic resonance imaging (CMRI) data from a healthy rat were used to obtain an end-diastolic biventricular geometry which was subsequently adjusted and combined with the injectate model. The computational geometry of the injectate exhibited microscopic structural details found the in situ. The combination of injectate and cardiac geometry provides realistic geometries for multiscale computational studies of intra-myocardial injectate therapies for the rat model that has been widely used for MI research. PMID:23682845

Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine

PubMed Central

Bradford, Emily M; Vairamani, Kanimozhi; Shull, Gary E

2016-01-01

AIM: To investigate the intestinal functions of the NKCC1 Na+-K+-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. RESULTS: Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION: The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors. PMID:26909237

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

PubMed

Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

2013-11-01

Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

PubMed

Inoue, Ken; Naito, Yuji; Takagi, Tomohisa; Hayashi, Natsuko; Hirai, Yasuko; Mizushima, Katsura; Horie, Ryusuke; Fukumoto, Kohei; Yamada, Shinya; Harusato, Akihito; Hirata, Ikuhiro; Omatsu, Tatsushi; Yoshida, Naohisa; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Handa, Osamu; Konishi, Hideyuki; Wakabayashi, Naoki; Yagi, Nobuaki; Ichikawa, Hiroshi; Kokura, Satoshi; Yoshikawa, Toshikazu

2011-01-01

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

PubMed

Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

2016-09-01

Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics. Copyright © 2016 the American Physiological Society.

Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs.

PubMed

Hansen, Carl Frederik; Thymann, Thomas; Andersen, Anders Daniel; Holst, Jens Juul; Hartmann, Bolette; Hilsted, Linda; Langhorn, Louise; Jelsing, Jacob; Sangild, Per Torp

2016-04-15

Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesarean-delivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16-64 ml·kg(-1)·day(-1) of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26 The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n = 8-12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0-5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay. Copyright © 2016 the American Physiological Society.

Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment.

PubMed

Da Silva, Stéphanie; Robbe-Masselot, Catherine; Ait-Belgnaoui, Afifa; Mancuso, Alessandro; Mercade-Loubière, Myriam; Salvador-Cartier, Christel; Gillet, Marion; Ferrier, Laurent; Loubière, Pascal; Dague, Etienne; Theodorou, Vassilia; Mercier-Bonin, Muriel

2014-08-15

Despite well-known intestinal epithelial barrier impairment and visceral hypersensitivity in irritable bowel syndrome (IBS) patients and IBS-like models, structural and physical changes in the mucus layer remain poorly understood. Using a water avoidance stress (WAS) model, we aimed at evaluating whether 1) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans, and related mucus physical properties, and 2) whether Lactobacillus farciminis treatment prevented these alterations. Wistar rats received orally L. farciminis or vehicle for 14 days; at day 10, they were submitted to either sham or 4-day WAS. Intestinal paracellular permeability and visceral sensitivity were measured in vivo. The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ. The mucin O-glycosylation profile was obtained by mass spectrometry. Surface imaging of intestinal mucus was performed at nanoscale by atomic force microscopy. WAS induced gut hyperpermeability and visceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expression. In contrast, O-glycosylation of mucins was strongly affected, with the appearance of elongated polylactosaminic chain containing O-glycan structures, associated with flattening and loss of the mucus layer cohesive properties. L. farciminis bound to intestinal Muc2 and prevented WAS-induced functional alterations and changes in mucin O-glycosylation and mucus physical properties. WAS-induced functional changes were associated with mucus alterations resulting from a shift in O-glycosylation rather than from changes in mucin expression. L. farciminis treatment prevented these alterations, conferring epithelial and mucus barrier strengthening. Copyright © 2014 the American Physiological Society.

Maintenance of Distal Intestinal Structure in the Face of Prolonged Fasting: A Comparative Examination of Species From Five Vertebrate Classes.

PubMed

McCue, Marshall D; Passement, Celeste A; Meyerholz, David K

2017-12-01

It was recently shown that fasting alters the composition of microbial communities residing in the distal intestinal tract of animals representing five classes of vertebrates [i.e., fishes (tilapia), amphibians (toads), reptiles (leopard geckos), birds (quail), and mammals (mice)]. In this study, we tested the hypothesis that the extent of tissue reorganization in the fasted distal intestine was correlated with the observed changes in enteric microbial diversity. Segments of intestine adjacent to those used for the microbiota study were examined histologically to quantify cross-sectional and mucosal surface areas and thicknesses of mucosa, submucosa, and tunica muscularis. We found no fasting-induced differences in the morphology of distal intestines of the mice (3 days), quail (7 days), or geckos (28 days). The toads, which exhibited a general increase in phylogenetic diversity of their enteric microbiota with fasting, also exhibited reduced mucosal circumference at 14 and 21 days of fasting. Tilapia showed increased phylogenetic diversity of their enteric microbiota, and showed a thickened tunica muscularis at 21 days of fasting; but this morphological change was not related to microbial diversity or absorptive surface area, and thus, is unlikely to functionally match the changes in their microbiome. Given that fasting caused significant increases and reductions in the enteric microbial diversity of mice and quail, respectively, but no detectable changes in distal intestine morphology, we conclude that reorganization is not the primary factor shaping changes in microbial diversity within the fasted colon, and the observed modest structural changes are more related to the fasted state. Anat Rec, 300:2208-2219, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

B Lymphocyte intestinal homing in inflammatory bowel disease

PubMed Central

2011-01-01

Background Inflammatory bowel disease (IBD) is thought to be due to an abnormal interaction between the host immune system and commensal microflora. Within the intestinal immune system, B cells produce physiologically natural antibodies but pathologically atypical anti-neutrophil antibodies (xANCAs) are frequently observed in patients with IBD. The objective is to investigate the localisation of immunoglobulin-producing cells (IPCs) in samples of inflamed intestinal tissue taken from patients with IBD, and their possible relationship with clinical features. Methods The IPCs in small intestinal, colonic and rectal biopsy specimens of patients with IBD were analysed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The B cell phenotype of the IPC-positive samples was assessed using monoclonal antibodies specific for CD79, CD20, CD23, CD21, CD5, λ and κ chains. Statistical correlations were sought between the histological findings and clinical expression. Results The study involved 96 patients (64 with ulcerative colitis and 32 with Crohn's disease). Two different patterns of B lymphocyte infiltrates were found in the intestinal tissue: one was characterised by a strong to moderate stromal localisation of small IgM+/CD79+/CD20-/CD21-/CD23-/CD5± IPCs (42.7% of cases); in the other (57.3%) no such small IPCs were detected in stromal or epithelial tissues. IPCs were significantly less frequent in the patients with Crohn's disease than in those with ulcerative colitis (p = 0.004). Conclusion Our findings suggest that different immunopathogenetic pathways underlie chronic intestinal inflammation with different clinical expressions. The presence of small B lymphocytes resembling B-1 cells also seemed to be negatively associated with Crohn's disease. It can therefore be inferred that the gut contains an alternative population of B cells that have a regulatory function. PMID:22208453

Modulation of small intestinal homeostasis along with its microflora during acclimatization at simulated hypobaric hypoxia.

PubMed

Adak, Atanu; Ghosh; Mondal, Keshab Chandra

2014-11-01

At high altitude (HA) hypobaric hypoxic environment manifested several pathophysiological consequences of which gastrointestinal (GI) disorder are very common phenomena. To explore the most possible clue behind this disorder intestinal flora, the major player of the GI functions, were subjected following simulated hypobaric hypoxic treatment in model animal. For this, male albino rats were exposed to 55 kPa (approximately 4872.9 m) air pressure consecutively for 30 days for 8 h/day and its small intestinal microflora, their secreted digestive enzymes and stress induced marker protein were investigated of the luminal epithelia. It was observed that population density of total aerobes significantly decreased, but the quantity of total anaerobes and Escherichia coli increased significantly after 30 days of hypoxic stress. The population density of strict anaerobes like Bifidobacterium sp., Bacteroides sp. and Lactobacillus sp. and obligate anaerobes like Clostridium perfringens and Peptostreptococcus sp. were expanded along with their positive growth direction index (GDI). In relation to the huge multiplication of anaerobes the amount of gas formation as well as content of IgA and IgG increased in duration dependent manner. The activity of some luminal enzymes from microbial origin like a-amylase, gluco-amylase, proteinase, alkaline phosphatase and beta-glucuronidase were also elevated in hypoxic condition. Besides, hypoxia induced in formation of malondialdehyde along with significant attenuation of catalase, glutathione peroxidase, superoxide dismutase activity and lowered GSH/GSSG pool in the intestinal epithelia. Histological study revealed disruption of intestinal epithelial barrier with higher infiltration of lymphocytes in lamina propia and atrophic structure. It can be concluded that hypoxia at HA modified GI microbial imprint and subsequently causes epithelial barrier dysfunction which may relate to the small intestinal dysfunction at HA.

Morphological and functional alterations of small intestine in chronic pancreatitis.

PubMed

Gubergrits, Natalya B; Linevskiy, Yuri V; Lukashevich, Galina M; Fomenko, Pavel G; Moroz, Tatyana V; Mishra, Tapan

2012-09-10

The small intestine in chronic pancreatitis has not been investigated yet thoroughly. It would be important to understand fat metabolism in the course of this disease and could be explained if the small intestine has some pathological conditions and, due to this reason, pancreatic enzyme substitution does not work in all patients. To investigate the pathophysiology of small intestine in chronic pancreatitis and to show the reason why in some cases pancreatic enzyme substitution does not work properly. In the process of the study 33 chronic pancreatitis patients have been examined. The control group includes 30 subjects without chronic pancreatitis similar for age, sex and alcohol consumption to the patients with chronic pancreatitis patients. Aspiration biopsy of jejunum mucosa followed by histological examination and investigation of intestinal enzymes by aspiration has been performed. Metabolism at membranic level has been studied by enzymatic activity of amylase and lipase in the small intestine. Production of enzymes (monoglyceride lipase, lactase, saccharase, maltase, glycyl-l-leucine dipeptidase) promoting metabolism in enterocytes has been estimated as to their activity in homogenates of jejunum mucosa samples. Participation of mucosa in intestinal digestion has been assessed by alkaline phosphatase activity in a secretory chyme from proximal portion of jejunum. Absorptive capacity of jejunum was evaluated by D-xylose test results. DNA, lysozyme, immunoglobulin contents of chyme have also been calculated and bacteriological study of chyme has been also performed. Secondary enteritis, accompanied by moderate dystrophic changes of mucous membrane, thinning of limbus, and decrease of Paneth cell mitotic index, was found to occur in chronic pancreatitis patients. Enteritis is followed by changes in enzymatic processes in the sphere of membrane and intestinal digestion, decrease of absorption, accelerated desquamation of epithelium, fall in local immunity and development of bacterial overgrowth syndrome. Existence of secondary enteritis and bacterial overgrowth syndrome validates lack of enzyme replacement therapy efficacy in some chronic pancreatitis patients with pancreatic insufficiency. To optimize treatment in such cases it is important to perform small intestine decontamination and escalate enzyme preparation dosage.

Comparative study of the digestive system of three species of tinamou. I. Crypturellus tataupa, Nothoprocta cinerascens, and Nothura maculosa (Aves: tinamidae).

PubMed

Chikilian, M; De Speroni, N B

1996-04-01

The morphology and histology, as well as the cytochemistry of complex carbohydrates, of the digestive system of Crypturellus tataupa (tataupa tinamou), Nothoprocta cinerascens (brushland tinamou), and Nothura maculosa (spotted tinamou) are described. The general morphology of the digestive system of these birds follows the basic model of the avian alimentary canal, although statistical analysis shows that the lengths of the organs are significantly different among the species. From cephalic to caudal regions the alimentary tract consists of esophagus, ingluvies or crop, proventriculus or glandular stomach, ventriculus or muscular stomach, small intestine, well-developed ceca, and rectum. Histologically, each section of the tract consists of four primary tissue layers: mucosa, submucosa, muscularis, and adventitia. Variations are found in the thickness of the esophageal epithelium, which shows the highest value in C. tataupa. In the proventriculus, the depth of the compound glands is greatest in N. cinerascens. The villi of the epithelial cells in the small intestine are most extensively developed in C. tataupa. Heterogeneity of mucins is detected not only in the surface coat of the alimentary tract but in the cellular content of the glands as well. Comparisons with the morphology of the digestive system of closely related and more advanced birds are made, and the possible relationship between morphological and cytochemical variation and the diet is discussed.

Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model

PubMed Central

Nahidi, Lily; Leach, Steven T.; Mitchell, Hazel M.; Kaakoush, Nadeem O.; Lemberg, Daniel A.; Munday, John S.; Huinao, Karina; Day, Andrew S.

2013-01-01

Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn's disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10−/− mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-α and myeloperoxidase plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls P < 0.05). Conclusion. H. trogontum infection in IL-10−/− mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes. PMID:24027765

[Risk factors associated to diffuse gastric cancer and intestinal histological patterns in an adult population from Western Mexico].

PubMed

Delgado-Figueroa, Netzahualpilli; Casas-Junco, Paloma; Torres-Jasso, Juan Heriberto; Bustos-Carpinteyro, Andrea Rebeca; Santiago-Luna, Ernesto; Marín-Contreras, María Eugenia; Sánchez-López, Josefina Yoaly

Gastric cancer (GC) is the third leading cause of cancer death worldwide, and is divided histologically in diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC). Multiple risk factors have been associated with GC in different populations. The objective was to analyze the risk factors associated to DGC and IGC in a population from the western region of Mexico. The DGC (n = 27) and IGC (n = 26) cases, each matched by age and sex with a control group, were analyzed. Diet and lifestyle data were obtained by a questionnaire. Statistical analysis was performed with the software SPSSv18. The association of risk was calculated in odds ratio (OR); a value of p < 0.05 was considered significant. In the DGC group, the factors with significant OR values were: consumption of pork OR: 3.4 (1.11-10.4; p =0.032), smoking OR: 4.7 (1.5-15.0; p =0.007), green vegetables OR: 0.16 (0.03-0.83; p =0.029) and fruit OR: 0.28 (0.08-0.88; p =0.029). In the IGC group, the consumption of canned sardines was a significant risk factor OR: 4.07 (1.25-13.24; p =0.019). This work is the first to analyze the risk factors associated with GC in a population from western Mexico.

Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic

PubMed Central

Mandys, Václav

2014-01-01

Objective. To characterize GEP-NENs in routine biopsies and surgical specimen in the Czech Republic and to evaluate how WHO Classification (2010) is acceptable in diagnostic practice. Methods. Paraffin-embedded blocks and bioptic reports were collected from 17 departments of pathology. Histologic slides were stained with H&E and immunohistologically for CgA, synaptophysin, and Ki-67. Results. Out of 28 gastric NENs, there were 22 NETs, G1, 5 NETs, G2, and 1 NEC. Ten duodenal NENs were NETs, G1. Among 27 NENs of jejunum and ileum, 23 were NETs, G1, 2 NETs, G2, and 1 NEC and 1 mixed adenoneuroendocrine carcinoma (MANEC). Among 42 appendiceal “incidentalomas”, 39 were NETs G1, 2 goblet cell carcinoids, and 1 MANEC. Out of 34 large intestinal NENs, 30 were NETs, G1, 3 NETs, G2, and 1 NEC. One small intestinal and 6 large bowel neoplasms were reclassified as poorly differentiated adenocarcinomas. In 12 pancreatic NENs, there were 7 NETs, G1, 3 NETs, G2, and 2 NECs. Conclusions. Our study demonstrates differences in GEP-NENs frequency in sites of origin in our region, comparing to other countries. Regarding routine bioptic diagnostics, we gave evidence that the WHO 2010 classification of NENs is fully acceptable for exact categorisation of tumours. PMID:24695372

A distinct variant of papillary thyroid carcinoma indicating familial adenomatous polyposis (FAP): a case report and brief review.

PubMed

Liyanapathirana, Nishantha; Seneviratne, Sanjeewa Anuruddha; Samarasekera, Dharmabandhu Nandadeva

2015-12-17

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra-intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well-established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms.

Gender differences in substrate utilisation during exercise.

PubMed

Ruby, B C; Robergs, R A

1994-06-01

The selection and utilisation of metabolic substrates during endurance exercise are regulated by a complex array of effectors. These factors include, but are not limited to, endurance training and cardiorespiratory fitness, exercise intensity and duration, muscle morphology and histology, hormonal factors and diet. Although the effects of these factors on substrate utilisation patterns are well understood, the variation in substrate utilisation during endurance exercise between males and females is not. Because of the extreme heterogeneity in exercise protocols and individuals studied, the differences in substrate utilisation between males and females remain somewhat inconclusive. Regardless of heterogeneity, if the results from studies are interpreted collectively, an apparent gender difference in the selection and metabolism of substrates can be seen in sedentary individuals. However, this difference between genders diminishes as the level of cardiorespiratory fitness is increased to that of highly trained individuals. During rest and lower intensity exercise, the preferential metabolism of lipid occurs with a concomitant sparing of muscle glycogen. However, as the intensity of exercise is increased, the relative contribution of carbohydrate also increases. The exercise intensity at which the shift from lipid to carbohydrate is determined and regulated by the previously mentioned factors. Because the intensity and duration of exercise play a predominant role, the variation in exercise protocols poses a methodological concern when interpreting previous research. When attempting to compare the metabolism of substrates during endurance exercise, appropriate selection and interpretation of measurement techniques are necessary. Measurement techniques include the nonprotein respiratory exchange ratio, muscle and fat biopsies and the measurement of various blood metabolites, such as free fatty acids and glycerol. Similarly, in vitro analysis of lipolytic activity has also been demonstrated in males and females in response to varying levels of female gonadotrophic hormones. When comparing the substrate utilisation patterns between males and females, the area of hormonal regulation has received less attention. Often the catecholamine response to endurance exercise is measured; however, the gonadotrophic hormones, particularly those of the female, have received less attention when comparing genders. Indeed, the regulatory nature of the female gonadotrophic hormones has been demonstrated. Collectively, the effects of elevated estrogen, as in the luteal phase of menstruation, appear to promote lipolytic activity. Estrogen-mediated lipolytic activation occurs by apparently altering the sensitivity to lipoprotein lipase and by increasing the levels of human growth hormone (somatotropin), an activator of lipolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Review article: the many potential roles of intestinal serotonin (5-hydroxytryptamine, 5-HT) signalling in inflammatory bowel disease.

PubMed

Coates, M D; Tekin, I; Vrana, K E; Mawe, G M

2017-09-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of every major gut-related function. Recent investigations also suggest that 5-HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD). To review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD. We reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5-HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5-HT signalling elements within the gut. Inflammation appears to affect every major element of intestinal 5-HT signalling, including 5-HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5-HT 4 R and antagonism of 5-HT 3 R) or 5-HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner. Insights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5-HT in this setting. © 2017 John Wiley & Sons Ltd.

Magnolol and Honokiol Attenuate Apoptosis of Enterotoxigenic Escherichia Coli-Induced Intestinal Epithelium by Maintaining Secretion and Absorption Homeostasis and Protecting Mucosal Integrity.

PubMed

Deng, Yanli; Han, Xuefeng; Tang, Shaoxun; Li, Chengjian; Xiao, Wenjun; Tan, Zhiliang

2018-05-21

BACKGROUND The cortex of Magnolia officinalis has long been used as an element of traditional Chinese medicine for the treatment of anxiety, chronic bronchitis, and gastrointestinal dysfunction. This study aimed to elucidate the underlying mechanism of its functional ingredients (magnolol and honokiol) in modifying the secretion and absorption homeostasis and protecting mucosal integrity in an Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mouse model. MATERIAL AND METHODS This study established a diarrhea mouse model infected by ETEC at a dosage of 0.02 ml/g live body weight (BW) in vivo. Magnolol or honokiol was followed by an intraperitoneal administration at dosages of 100, 300, and 500 mg/kg BW according to a 3×3 factorial arrangement. The useful biomarkers for evaluating the integrity of intestinal tract and histologic injury were analyzed and morphological development (including villus height, crypt depth, and ratio of villus height to crypt depth) and the expressions of inflammatory cytokines were determined by real-time PCR. RESULTS The results showed that magnolol and honokiol (500 mg/kg BW) reduced the concentrations of NO, DAO, and DLA, and iNOS activity, and the mRNA expressions of the interferon gamma (IFN-γ) and interleukin 10 (IL-10), and inhibited intestinal epithelial cell apoptosis. Magnolol and honokiol (300 mg/kg BW) elongated the villus height and crypt depth and decreased the number of goblet cells and the ratio of villus height to crypt depth. CONCLUSIONS The current results indicate that magnolol and honokiol enhance the intestinal anti-inflammatory capacities, elongate the villus height and crypt depth, and reduce goblet cell numbers to inhibit the intestinal epithelium apoptosis and effectively protect the intestinal mucosa. These results show that magnolol and honokiol protect the intestinal mucosal integrity and regulate gastrointestinal dysfunction.

Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.

PubMed

Flora, Alyssa D; Teel, Louise D; Smith, Mark A; Sinclair, James F; Melton-Celsa, Angela R; O'Brien, Alison D

2013-01-01

Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.

Ricin Crosses Polarized Human Intestinal Cells and Intestines of Ricin-Gavaged Mice without Evident Damage and Then Disseminates to Mouse Kidneys

PubMed Central

Flora, Alyssa D.; Teel, Louise D.; Smith, Mark A.; Sinclair, James F.; Melton-Celsa, Angela R.; O’Brien, Alison D.

2013-01-01

Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock. PMID:23874986

Optimal Solution Volume for Luminal Preservation: A Preclinical Study in Porcine Intestinal Preservation.

PubMed

Oltean, M; Papurica, M; Jiga, L; Hoinoiu, B; Glameanu, C; Bresler, A; Patrut, G; Grigorie, R; Ionac, M; Hellström, M

2016-03-01

Rodent studies suggest that luminal solutions alleviate the mucosal injury and prolong intestinal preservation but concerns exist that excessive volumes of luminal fluid may promote tissue edema. Differences in size, structure, and metabolism between rats and humans require studies in large animals before clinical use. Intestinal procurement was performed in 7 pigs. After perfusion with histidine-tryptophan-ketoglutarate (HTK), 40-cm-long segments were cut and filled with 13.5% polyethylene glycol (PEG) 3350 solution as follows: V0 (controls, none), V1 (0.5 mL/cm), V2 (1 mL/cm), V3 (1.5 mL/cm), and V4 (2 mL/cm). Tissue and luminal solutions were sampled after 8, 14, and 24 hours of cold storage (CS). Preservation injury (Chiu score), the apical membrane (ZO-1, brush-border maltase activity), and the electrolyte content in the luminal solution were studied. In control intestines, 8-hour CS in HTK solution resulted in minimal mucosal changes (grade 1) that progressed to significant subepithelial edema (grade 3) by 24 hours. During this time, a gradual loss in ZO-1 was recorded, whereas maltase activity remained unaltered. Moreover, variable degrees of submucosal edema were observed. Luminal introduction of high volumes (2 mL/mL) of PEG solution accelerated the development of the subepithelial edema and submucosal edema, leading to worse histology. However, ZO-1 was preserved better over time than in control intestines (no luminal solution). Maltase activity was reduced in intestines receiving luminal preservation. Luminal sodium content decreased in time and did not differ between groups. This PEG solution protects the apical membrane and the tight-junction proteins but may favor water absorption and tissue (submucosal) edema, and luminal volumes >2 mL/cm may result in worse intestinal morphology. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

PubMed

Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza

2015-12-01

Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models. Concentrations from 0.1 to 10 mM of anionic and cationic dendrimers were tested in mucosae to assess their Papp, membrane TEER, [(14)C]-mannitol Papp, and histology. 0.1 mM concentrations of dendrimers were assessed over 120 min in Caco-2 cell monolayers as concentrations above that were cytotoxic. Jejunal transport of dendrimers was higher than transport in colonic epithelium. Monolayer Papp values of dendrimers were comparable to those of jejunal mucosae. Mucosae exposed to dendrimer concentrations of 10 mM for 120 min caused significant reduction in TEER and changes in tissue morphology; however, G3.5 was the only analogue that caused significant TEER reduction and morphological changes at 1 mM concentrations. Transport in jejunal mucosae appears to be the greatest indicating that the small intestinal will be the most likely region to target for oral drug delivery using PAMAM dendrimers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The trophic effect of epidermal growth factor on morphological changes and polyamine metabolism in the small intestine of rats.

PubMed

Tsujikawa, T; Bamba, T; Hosoda, S

1990-06-01

This study was undertaken to evaluate the effect of epidermal growth factor (EGF) on the morphological changes and polyamine metabolism in the atrophic small intestinal mucosa of rats caused by feeding elemental diet (ED; Elental, Ajinomoto, Tokyo) for several weeks. Four-week-old Wistar male rats were given ad libitum ED (1 kcal/ml) for 4 weeks. The body weight increased to the same extent as the control group fed a pellet diet. However, the small intestine became atrophic: the mucosal wet weight of the jejunum decreased to 70%, while that of the ileum decreased to 60%. EGF (10 micrograms/kg) was subcutaneously injected into these rats every 8 hours. Ornithine decarboxylase (ODC) activities of the jejunal and ileal mucosa rose within 12 hours of the initial EGF administration. Mucosal DNA specific activities tended to increase. Next, EGF (30 micrograms/kg/day) was intraperitoneally administered with a Mini-osmotic pump for one week. The wet weight, protein and DNA contents of the ileal mucosa increased significantly compared with those of the saline administered controls, while the crypt cell production rate (CCPR) also increased. Histologically, increases in both villus height and crypt depth were confirmed. These findings indicate that EGF causes mucosal proliferation through polyamine metabolism even in the atrophic small intestine of mature rats after ED administration for 4 weeks.

Sodium selenite ameliorates both intestinal and extra-intestinal changes in acetic acid-induced colitis in rats.

PubMed

Soliman, Samar M; Wadie, Walaa; Shouman, Samia A; Ainshoka, Afaf A

2018-06-01

Selenium and its derivatives including sodium selenite (sod sel) belong to the group of essential trace elements needed for proper health and nutrition. They are fairly safe and possess antioxidant and anti-inflammatory properties. The aim of present investigation was to elucidate the effect of sod sel on experimental colitis model in rats. Colitis was induced by intrarectal instillation of 4% (v/v) acetic acid. Two hours later, sod sel was given to rats on a daily basis for 15 consecutive days. Clinical symptoms, colon mass index, spleen weight inflammatory markers, hematological, biochemical, macroscopic, and histological changes were determined. Sod sel markedly ameliorated colitis as evidenced by a significant decrease in macroscopic and microscopic score, disease activity index, colon mass index, and spleen weight. Treatment with sod sel attenuated oxidative stress in the colon by normalizing the colonic content of nitric oxide, malondialdehyde, and reduced glutathione, as well as the activities of catalase, superoxide dismutase, and junctional adhesion molecule (JAM-a). In addition, it significantly reduced colonic myeloperoxidase content, the intercellular adhesion molecule (ICAM-1), and the proinflammatory cytokines; TNF-α, IL-1β. Moreover, sod sel normalized hematological parameters, serum transaminases, and kidney and liver function enzymes. The current study indicates that sod sel was effective in ameliorating the intestinal and extra-intestinal manifestation in acetic acid-induced colitis through its antioxidant, anti-inflammatory, and immunomodulatory effects.

Intestinal mucin dynamics: response of broiler chicks and White Pekin ducklings to dietary threonine.

PubMed

Horn, N L; Donkin, S S; Applegate, T J; Adeola, O

2009-09-01

Mucin dynamics may be particularly sensitive to a Thr deficiency due to the high concentration and structural importance of Thr in the mucin protein backbone. Intestinal mucin secretion, expression of mucin gene (MUC2), and histological characteristics were investigated in male broilers and White Pekin ducklings offered diets containing 3.3, 5.8, or 8.2 g of Thr/kg in 4 studies. Seventy-two birds of each species were fed a standard broiler starter diet from 1 to 14 d of age followed by assignment to 3 dietary treatments in a randomized complete block design for a 7-d feeding trial in experiment 1 (broilers) and experiment 2 (ducklings). The dietary treatments consisted of an isonitrogenous corn-soybean meal-based diet with the addition of crystalline amino acids and graded levels of Thr. Dietary treatments contained 3.3, 5.8, or 8.2 g of Thr/kg. Dietary formulation and experimental design for experiments 3 (broilers) and 4 (ducklings) were similar to experiments 1 and 2 except that birds were fed 3.3 or 8.2 g of Thr/kg for durations of 7 or 14 d. For chicks, increased dietary Thr resulted in higher levels of intestinal crude mucin excretion in experiment 1 (P=0.04) but not in experiment 3, whereas intestinal sialic acid excretion increased in experiment 3 (P=0.02) but not in experiment 1. Furthermore, there was no effect of Thr on intestinal goblet cell density or MUC2 mRNA abundance for broilers. For ducklings, there was an increase in intestinal crude mucin excretion in both experiments (P<0.05) as dietary Thr increased, although there was no effect of Thr on intestinal sialic acid excretion. There was a tendency for an increase in intestinal goblet cell density (cells/microm of villus length; P=0.09) as dietary Thr increased in experiment 2. For experiment 4, intestinal MUC2 mRNA abundance increased (P=0.03) as dietary Thr increased for the 14-d feeding trial but not for the 7-d feeding trial. The data establish a link between dietary Thr and intestinal crude mucin dynamics in chicks for experiment 1 and ducklings for both experiments.

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Jian; Zhang, Lin; Dai, Weiqi

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and alsomore » prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.« less

Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats.

PubMed

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

2017-04-01

Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats

PubMed Central

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J.; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

2018-01-01

Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer’s patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+ cells as well. In cocoa-fed animals, we identified a five time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+ cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect. PMID:28189917

Shape memory alloy-based biopsy device for active locomotive intestinal capsule endoscope.

PubMed

Le, Viet Ha; Hernando, Leon-Rodriguez; Lee, Cheong; Choi, Hyunchul; Jin, Zhen; Nguyen, Kim Tien; Go, Gwangjun; Ko, Seong-Young; Park, Jong-Oh; Park, Sukho

2015-03-01

Recently, capsule endoscopes have been used for diagnosis in digestive organs. However, because a capsule endoscope does not have a locomotive function, its use has been limited to small tubular digestive organs, such as small intestine and esophagus. To address this problem, researchers have begun studying an active locomotive intestine capsule endoscope as a medical instrument for the whole gastrointestinal tract. We have developed a capsule endoscope with a small permanent magnet that is actuated by an electromagnetic actuation system, allowing active and flexible movement in the patient's gut environment. In addition, researchers have noted the need for a biopsy function in capsule endoscope for the definitive diagnosis of digestive diseases. Therefore, this paper proposes a novel robotic biopsy device for active locomotive intestine capsule endoscope. The proposed biopsy device has a sharp blade connected with a shape memory alloy actuator. The biopsy device measuring 12 mm in diameter and 3 mm in length was integrated into our capsule endoscope prototype, where the device's sharp blade was activated and exposed by the shape memory alloy actuator. Then the electromagnetic actuation system generated a specific motion of the capsule endoscope to extract the tissue sample from the intestines. The final biopsy sample tissue had a volume of about 6 mm(3), which is a sufficient amount for a histological analysis. Consequently, we proposed the working principle of the biopsy device and conducted an in-vitro biopsy test to verify the feasibility of the biopsy device integrated into the capsule endoscope prototype using the electro-magnetic actuation system. © IMechE 2015.

Disseminated toxoplasmosis in black-footed penguins (Spheniscus demersus).

PubMed

Ploeg, Margreet; Ultee, Ton; Kik, Marja

2011-12-01

Three 1- to 3-mo-old black-footed penguins (Spheniscus Demersus) died within 24 hr of showing central nervous signs such as ataxia. The birds were housed in a baby penguin crèche. At necropsy, peritonitis, pneumonia, hepatomegaly, splenomegaly, and renomegaly were evident. Histologically, the liver, lung, brain, and small intestine contained numerous tachyzoites and a few cysts of Toxoplasma. Immunohistochemistry identified the protozoal parasites as Toxoplasma gondii. Ultrastructurally, this was confirmed by the presence of many tachyzoites of T. gondii in the liver and lungs.

CLINICOPATHOLOGIC CORRELATES OF FASCIOLIASIS IN TWO EASTERN GREY KANGAROOS (MACROPUS GIGANTEUS).

PubMed

Portas, Timothy J; Taylor, David

2015-12-01

Infection with the introduced trematode Fasciola hepatica was associated with anemia, mild to moderate azotemia, hypoalbuminemia, and elevated liver enzymes and creatine kinase values in two free-ranging eastern grey kangaroos (Macropus giganteus). Both kangaroos were euthanized because of the severity of clinical signs associated with infection. Histopathologic changes included severe cholangiohepatitis, biliary hyperplasia, and fibrosis. Hepatic, splenic, and intestinal amyloidosis was present in one kangaroo and hepatic abscessation in the other; neither histologic change has been reported in macropodids with fascioliasis previously.

Cerebral Scedosporium apiospermum infection presenting with intestinal manifestations.

PubMed

Lin, D; Kamili, Q; Qurat-Ul-Ain, K; Lai, S; Musher, D M; Hamill, R

2013-06-01

We present a case of cerebral Scedosporium apiospermum infection presenting with intestinal manifestations in a 64-year-old male patient on immunosuppression for orthotopic liver transplantation. At admission, the patient's chief complaint was chronic watery diarrhea and he was found to have colonic ulcers on endoscopy. His hospital course was complicated by a tonic-clonic seizure caused by a left frontal brain abscess, with the causative agent being identified by culture. He was treated with lobectomy, high-dose intravenous voriconazole, and liposomal amphotericin with clinical, endoscopic, and histologic improvement. To our knowledge, S. apiospermum has not been previously described as a cause of colitis. The septate branching appearance of the Scedosporium species is similar to the more common Aspergillus species. This case of gastrointestinal Scedosporium brings into question previously reported cases of isolated gastrointestinal aspergillosis diagnosed by histopathology. Clinical suspicion for S. apiospermum must be maintained in immunosuppressed patients presenting with neurologic and gastrointestinal symptoms.

Small Intestinal Submucosa Plug for Closure of Dilated Nephrostomy Tracts: A Pilot Study in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kakizawa, Hideyaki; Conlin, M. J.; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu

2010-06-15

The aim of this study was to evaluate efficacy of a plug made of small intestinal submucosa (SIS) for closure of dilated nephrostomy tract in the kidney after nephroscopy. Ten kidneys in 5 swine had nephrostomy tracts dilated up to 8 mm. The SIS plug was placed into the dilated renal cortex under nephroscopic control. Follow-up arteriograms, retrograde pyelograms, and macroscopic and histologic studies at 24 h (n = 4), 6 weeks (n = 2), and 3 months (n = 4) were performed to evaluate the efficacy of the plug. The SIS plug effectively closed the dilated nephrostomy tract. Follow-upmore » studies showed minimal changes of the kidneys, except for 1 small infarction, regarding inflammatory and foreign-body reactions and progressive scarring of the SIS. SIS plug is effective for occlusion of dilated nephrostomy tract after nephroscopy. Its efficacy should be compared with other therapeutic options.« less

The Drosophila Nora virus is an enteric virus, transmitted via feces.

PubMed

Habayeb, Mazen S; Cantera, Rafael; Casanova, Gabriela; Ekström, Jens-Ola; Albright, Shannon; Hultmark, Dan

2009-04-01

The biology of the Drosophila viruses has not been intensely investigated. Here we have investigated the biology of the Nora virus, a persistent Drosophila virus. We find that injected Nora virus is able to replicate in the files, reaching a high titer that is maintained in the next generation. There is a remarkable variation in the viral loads of individual flies in persistently infected stocks; the titers can differ by three orders of magnitude. The Nora virus is mainly found in the intestine of infected flies, and the histology of these infected intestines show increased vacuolization. The virus is excreted in the feces and is horizontally transmitted. The Nora virus infection has a very mild effect on the longevity of the flies, and no significant effect on the number of eggs laid and the percent of eggs that develop to adults.

Endogenous Life Cycle of Eimeria melanomytis (Apicomplexa: Eimeriidae) from the Dusky Rice Rat, Melanomys caliginosus (Rodentia: Cricetidae: Sigmodontinae) in Costa Rica.

PubMed

Chinchilla, Misael; Valerio, Idalia; Sánchez, Ronald; Duszynski, Donald W

2017-02-01

Endogenous stages of the life cycle of Eimeria melanomytis, infecting the peripheral epithelial cells of villi of the small intestine of experimentally infected young dusky rice rats, Melanomys caliginosus , were studied. Giemsa-stained mucosal scrapings and histological sections were examined for all the stages. Eimeria melanomytis has 3 generations of meronts (M), different in size, shape, and number of merozoites (m); and in size, shape, and location of the nuclei within the cytoplasm of the meronts. The 3 meront types, M 1 -M 3 , respectively, had 11-14 (m 1 ), 7-10 (m 2 ), and 20-30 (m 3 ) merozoites. Macrogametocytes and microgametocytes, as well as macrogametes and microgametes, complete the sexual cycle forming the unsporulated oocysts. This parasite's endogenous development produced severe intestinal lesions in experimentally infected dusky rice rats.

Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility

PubMed Central

Nassif, A.; Sexe, R.; Stratton, M.; Standeven, J.; Vernava, A. M.; Kaminski, D. L.

1995-01-01

We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10−8 M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E2 and thromboxane B2. Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation. PMID:18475679

Label-free identification of intestinal metaplasia in the stomach using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Wu, G.; Wei, J.; Zheng, Z.; Ye, J.; Zeng, S.

2014-06-01

The early diagnosis of intestinal metaplasia (IM) in the stomach together with effective therapeutic interventions is crucial to reducing the mortality-rates of the patients associated with gastric cancer. However, it is challenging during conventional white-light endoscopy, and histological analysis remains the ‘gold standard’ for the final diagnosis. Here, we describe a label-free imaging method, multiphoton microscopy (MPM), for the identification of IM in the stomach. It was found that multiphoton imaging provides cellular and subcellular details to the identification of IM from normal gastric tissues. In particular, there is significant difference in the population density of goblet cells between normal and IM gastric tissues, providing substantial potential to become a quantitative intrinsic marker for in vivo clinical diagnosis of early gastric lesions. To our knowledge, this is the first demonstration of the potential of MPM for the identification of IM.

Grape Seed Extract Dose-Responsively Decreases Disease Severity in a Rat Model of Mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells

PubMed Central

Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

2014-01-01

Objective Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Design Female Dark Agouti rats were gavaged with grape seed extract (400–1000 mg/kg) or water (day 3–11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Results Compared with 5-Fluorouracil controls, grape seed extract (400–1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10–25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50–100 µg/mL. Conclusion Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells. PMID:24465501

Detection and Localisation of the Abalone Probiotic Vibrio midae SY9 and Its Extracellular Protease, VmproA, within the Digestive Tract of the South African Abalone, Haliotis midae

PubMed Central

Huddy, Robert J.; Coyne, Vernon E.

2014-01-01

Probiotics have been widely reported to increase the growth rate of commercially important fish and shellfish by enhancing the digestion of ingested feed through the production of extracellular enzymes such as proteases and alginases. In order to investigate this further, the objective of this study was to localise the bacterial probiont Vibrio midae SY9 and one of the extracellular proteases it produces in the digestive tract of the South African abalone Haliotis midae. This was accomplished by inserting a promotorless gfp gene into the chromosome of the bacterium which was incorporated in an artificial, fishmeal-based abalone feed. In situ histological comparison of abalone fed either a basal diet or the basal diet supplemented with V. midae SY9::Tn10.52 using a cocktail of DNA probes to the gfp gene localised the probiont to the crop/stomach and intestinal regions of the H. midae digestive tract. Generally, the ingested probiotic bacterium occurred in association with feed and particulate matter within the crop/stomach and intestinal regions, as well as adhered to the wall of the crop/stomach. Histological immunohistochemical examination using polyclonal anti-VmproA antibodies localised an extracellular protease produced by V. midae SY9 to the H. midae crop/stomach and intestine where it appeared to be associated with feed and/or other particulate matter in the abalone gut. Thus the data suggests that V. midae SY9 colonises and/or adheres to the mucous lining of the abalone gut. Furthermore, the close association observed between the bacterium, its extracellular protease and ingested feed particles supports the theory that V. midae SY9 elevates in situ digestive enzyme levels and thus enhances feed digestion in farmed abalone. PMID:24466176

The imbalance between regulatory and IL-17-secreting CD4⁺T cells in multiple-trauma rat.

PubMed

Dai, Heling; Sun, Tiansheng; Liu, Zhi; Zhang, Jianzheng; Zhou, Meng

2013-11-01

It has been well recognised that a deficit of numbers and function of CD4(+)CD25(+)Foxp3(+)cells (Treg) is attributed to the development of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue; however, there are controversial data regarding the suppressive effect of Treg cells on the T-cell response in auto-immune diseases. Additionally, interleukin-17 (IL-17)-producing cells (Th17) have a pro-inflammatory role. The balance between Th17 and Treg may be essential for maintaining immune homeostasis and has long been thought as one of the important factors in the development/prevention of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue, but their role in multiple trauma remains unclear. This study aims to investigate whether an imbalance of Treg and Th17 effector cells is characteristic of rats suffering from multiple trauma. Sixty Sprague-Dawley (SD) rats were randomly divided into three groups. The control group (n=20, group I) no received procedures (normal). The sham group (n=20, group II) only received anaesthesia, cannulation and observation. The bilateral femoral shaft fractures with haemorrhagic shock groups (n=20, group III). Rats in groups II and III were killed at the end of 4h after models were established. Peripheral blood samples were collected for assessment of Treg cells, Th17 cells and cytokines (IL-17, IL-6, IL-2, transforming growth factor beta (TGF-β)) and intestine tissue was collected for intestine histological analysis. We observed decreased Treg/Th17 ratios in CD4(+)T cells in rats with multiple trauma and a strong inverse correlation with disease activity (intestinal histological scores). We suggest a role for immune imbalance in the pathogenesis and development of multiple trauma. The alteration of the index of Treg/Th17 cells likely indicates the therapeutic response and progress in the clinic. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

PubMed

Jiménez Fonseca, Paula; Carmona-Bayonas, Alberto; Hernández, Raquel; Custodio, Ana; Cano, Juana Maria; Lacalle, Alejandra; Echavarria, Isabel; Macias, Ismael; Mangas, Monserrat; Visa, Laura; Buxo, Elvira; Álvarez Manceñido, Felipe; Viudez, Antonio; Pericay, Carles; Azkarate, Aitor; Ramchandani, Avinash; López, Carlos; Martinez de Castro, Eva; Fernández Montes, Ana; Longo, Federico; Sánchez Bayona, Rodrigo; Limón, Maria Luisa; Diaz-Serrano, Asun; Martin Carnicero, Alfonso; Arias, David; Cerdà, Paula; Rivera, Fernando; Vieitez, Jose Maria; Sánchez Cánovas, Manuel; Garrido, M; Gallego, J

2017-09-05

The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Bile components and lecithin supplemented to plant based diets do not diminish diet related intestinal inflammation in Atlantic salmon.

PubMed

Kortner, Trond M; Penn, Michael H; Bjӧrkhem, Ingemar; Måsøval, Kjell; Krogdahl, Åshild

2016-09-07

The present study was undertaken to gain knowledge on the role of bile components and lecithin on development of aberrations in digestive functions which seemingly have increased in Atlantic salmon in parallel with the increased use of plant ingredients in fish feed. Post smolt Atlantic salmon were fed for 77 days one of three basal diets: a high fish meal diet (HFM), a low fishmeal diet (LFM), or a diet with high protein soybean meal (HPS). Five additional diets were made from the LFM diet by supplementing with: purified taurocholate (1.8 %), bovine bile salt (1.8 %), taurine (0.4 %), lecithin (1.5 %), or a mix of supplements (suppl mix) containing taurocholate (1.8 %), cholesterol (1.5 %) and lecithin (0.4 %). Two additional diets were made from the HPS diet by supplementing with: bovine bile salt (1.8 %) or the suppl mix. Body and intestinal weights were recorded, and blood, bile, intestinal tissues and digesta were sampled for evaluation of growth, nutrient metabolism and intestinal structure and function. In comparison with fish fed the HFM diet fish fed the LFM and HPS diets grew less and showed reduced plasma bile salt and cholesterol levels. Histological examination of the distal intestine showed signs of enteritis in both LFM and HPS diet groups, though more pronounced in the HPS diet group. The HPS diet reduced digesta dry matter and capacity of leucine amino peptidase in the distal intestine. None of the dietary supplements improved endpoints regarding fish performance, gut function or inflammation in the distal intestine. Some endpoints rather indicated negative effects. Dietary supplementation with bile components or lecithin in general did not improve endpoints regarding performance or gut health in Atlantic salmon, in clear contrast to what has been previously reported for rainbow trout. Follow-up studies are needed to clarify if lower levels of bile salts and cholesterol may give different and beneficial effects, or if other supplements, and other combinations of supplements might prevent or ameliorate inflammation in the distal intestine.

Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans.

PubMed

Pereira, Dora I A; Bruggraber, Sylvaine F A; Faria, Nuno; Poots, Lynsey K; Tagmount, Mani A; Aslam, Mohamad F; Frazer, David M; Vulpe, Chris D; Anderson, Gregory J; Powell, Jonathan J

2014-11-01

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P < 0.0001) and direct in vitro cellular uptake (P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia. This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Se-Chul; Park, Jeong-Mi; Jang, Hong-Seok

Captopril, an inhibitor of angiotensin I converting enzyme, has been shown to modify radiation damage and prevent radiation injury of normal tissue in rats and pigs. The present study was carried out to determine whether captopril would reduce radiation changes in the proximal small bowel in mice. Mice were subjected to whole body irradiation with 9 Gy or 15 Gy. Captopril was administered in drinking water at a regimen of 62.5 mg/kg/day (captopril group I) and 125 mg/kg/day (captopril group II), continuously from 7 days before irradiation to the end of each designed experiment. The jejunal damage was evaluated microscopicallymore » by crypt count per circumference and by histologic damage grading. Crypt number in the sham-irradiated control was 133 {plus_minus} 6.8/circumference. In both captopril group I and II, crypt numbers and histologic scores were not significantly different from those in the normal group. The 9 Gy and 15 Gy radiation alone groups showed significantly lower crypt counts and histologic scores compared with the sham-irradiated control group (p<0.05). The groups exposed to 9 Gy radiation plus captopril I and II showed significantly higher crypt counts and lower histologic damage scores on the third day, and lower histologic damage scores on the fifth day compared with the 9 Gy radiation alone group (p<0.05). The 15 Gy radiation plus captopril I and II groups had significantly higher crypt counts and lower histologic damage scores on the third day than those of the 15 Gy radiation alone group (p<0.05). All mice of the 15 Gy radiation group succumbed to intestinal radiation death. Our results suggest that captopril provides protection from acute radiation damage to the jejunal mucosa in mice. 28 refs., 5 figs., 4 tabs.« less

Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.

PubMed

Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

2017-01-01

The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Helicobacter pylori, gastritis, and peptic ulceration in the elderly.

PubMed Central

Wyatt, J I; Shallcross, T M; Crabtree, J E; Heatley, R V

1992-01-01

AIMS: To determine the histopathological types of gastritis, presence of H pylori, and of peptic ulceration in patients aged 70 and over, compared with younger adults. METHODS: Gastric antral and corpus biopsy specimens from 112 elderly patients were classified and graded histologically according to the Sydney system. Details of recent antibiotic and non-steroidal anti-inflammatory drug use were recorded. Eighty four of the patients were positive for H pylori IgG antibodies and parietal cell antibodies. The results were compared with those from a series of 124 adult patients aged under 60. RESULTS: H pylori were visible at histological examination in only 57 of 87 (65.5%) elderly patients with chronic gastritis (excluding "special forms") compared with 72 of 79 (91.1%) of the younger patients with gastritis (p < 0.0002). Severe atrophy of the corpus mucosa was significantly associated with absence of H pylori (p < 0.002), and was present in eight of 30 elderly patients with helicobacter negative gastritis. Other explanations for absence of H pylori include recent antibiotic intake, more intestinal metaplasia, and lower bacterial load in elderly patients (p < 0.05). Autoimmune gastritis and NSAID use did not seem to be relevant. Serodiagnosis showed reduced sensitivity (81%) in patients who were helicobacter positive histologically, but was positive in 14 of 23 (61%) with H pylori negative gastritis histologically, suggesting either current infection that had been missed or previous infection. Peptic ulceration was significantly associated with NSAID use, but not with H pylori in the elderly. CONCLUSIONS: The spectrum of gastritis is different in the elderly, compared with younger adults, due to a significant group with chronic gastritis who are H pylori negative on histological examination. NSAID use, but not demonstration of H pylori (at histological examination) is associated with peptic ulceration in the elderly. PMID:1479032

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

PubMed Central

Watt, P C; Sloan, J M; Donaldson, J; Campbell, G; Kennedy, T L

1984-01-01

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes. PMID:6725597

EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus.

PubMed

Birkman, Eva-Maria; Ålgars, Annika; Lintunen, Minnamaija; Ristamäki, Raija; Sundström, Jari; Carpén, Olli

2016-07-07

Approximately 50 % of gastric adenocarcinomas belong to a molecular subgroup characterised by chromosomal instability and a strong association with the intestinal histological subtype. This subgroup typically contains alterations in the receptor tyrosine kinase-RAS pathway, for example EGFR or HER2 gene amplifications leading to protein overexpression. In clinical practice, HER2 overexpressing metastatic gastric cancer is known to respond to treatment with anti-HER2 antibodies. By contrast, anti-EGFR antibodies have not been able to provide survival benefit in clinical trials, which, however, have not included patient selection based on the histological subtype or EGFR gene copy number analysis of the tumours. To examine the role of EGFR as a potential biomarker, we studied the prevalence, clinicopathological associations as well as prognostic role of EGFR and HER2 expression and gene amplification in intestinal adenocarcinomas of the stomach, gastro-oesophageal junction and distal oesophagus. Tissue samples from 220 patients were analysed with EGFR and HER2 immunohistochemistry. Those samples with moderate/strong staining intensity were further analysed with silver in situ hybridization to quantify gene copy numbers. The results were associated with clinical patient characteristics and survival. Moderate/strong EGFR protein expression was found in 72/220 (32.7 %) and EGFR gene amplification in 31/220 (14.1 %) of the tumours, while moderate/strong HER2 protein expression was detected in 31/220 (14.1 %) and HER2 gene amplification in 29/220 (13.2 %) of the tumours. EGFR and HER2 genes were co-amplified in eight tumours (3.6 %). EGFR gene amplification was more common in tumours of distal oesophagus/gastro-oesophageal junction/cardia than in those of gastric corpus (p = 0.013). It was associated with shortened time to cancer recurrence (p = 0.026) and cancer specific survival (p = 0.033). EGFR gene amplification is relatively common in intestinal adenocarcinomas and associates with decreased survival. It is rarely concurrent with HER2 gene amplification, suggesting that anti-EGFR therapies might be applicable to some patients not eligible for anti-HER2 treatment. Analogous to HER2 testing, determination of EGFR gene amplification status in concert with immunohistochemistry could improve the specificity of patient selection when investigating the possible benefits of anti-EGFR therapies in the treatment of gastric adenocarcinomas.

Primary T-cell Lymphoma of the Colon

PubMed Central

Son, Hee Jung; Rhee, Poong Lyul; Kim, Jae-Jun; Koh, Kwang Choel; Paik, Seong Woon; Rhee, Jong Chul; Koh, Young Hae

1997-01-01

A 40-year-old woman had been diagnosed with Crohns disease in September 1994, but later examinations revealed a primary T-cell lymphoma of the colon. Colonoscopic and histological examination showed ulcerative lesions simulating Crohns disease involving the entire colon and the terminal ileum, and she was first diagnosed as having Crohns disease. Differential therapeutic strategies, including corticosteroid, had improved the symptoms which were dominated by abdominal pain. When she visited our institute in April 1995, she presented with bloody stool twice a day, 7kg weight loss in a period of six months and a slightly painful abdomen. Colonoscopic finding showed geographic ulceration on the entire colon, especially rectum and terminal ileum. The histologic examination of specimens from colonoscopic biopsy showed primary peripheral T-cell lymphoma of the colon. Any dense lymphocyte infiltrates seen in the biopsy specimens obtained from lesions simulating ulcerative colitis or Crohns disease should be assessed to exclude intestinal lymphoma PMID:9439161

Ectopic Enterobius Vermicularis Infestation; An Extremely Rare Cause Of Mesenteric Lymphadenopathy Mimicking Tuberculous Lymphadenitis.

PubMed

Zafar, Summaiya; Tariq, Muhammad Usman; Ahmed, Zubair

2018-01-01

Enterobius vermicularis (EV) is a pinworm which commonly resides in the lumen of the intestinal tract and lays eggs on the perianal skin. However, rarely the worm can infest various other sites in the body and cases with infestation of such ectopic sites have been reported in literature. Rare cases of mesenteric lymph node involvement have also been reported. We report a case in a young male who presented with signs and symptoms of acute appendicitis. During surgery, enlarged mesenteric lymph nodes were identified. Histological examination revealed adult worm in the appendiceal lumen. Histological examination of mesenteric lymph node revealed degenerated worm surrounded by caseating chronic granulomatous inflammation. We conclude that EV infestation should be considered in the differential diagnosis of enlarged mesenteric lymph node with chronic granulomatous inflammation, especially in young patients and when accompanying bowel tissue also reveal the helminth.

Gastroduodenitis and peptic ulcer in a rural Liberian community. An endoscopic prospective study.

PubMed

Stahel, E; Gyr, K; Jallah, E; Heitz, P

1981-06-01

In a prospective study on a Liberian rubber plantation lasting over 12 months, 79 consecutive patients with recurrent epigastric pain as well as 15 controls without evidence of gastrointestinal disease were endoscoped with a fiberoptic instrument. Peptic ulcers were found in 7 (9%) of the 79 patients; 3 were in the prepyloric antrum and 4 in the duodenal bulb. The incidence of symptomatic peptic ulcer disease estimated from the data was 0.15 per 1000 population per year. Histology revealed superficial gastritis in 34, atrophic gastritis in 23 and duodenitis in 23 of the patients and in 3, 2 and 1 respectively of the control group. The differences observed between patients and controls were statistically significant for the stomach (p less than 0.01) but not for the duodenum. No correlation was found between the presence of histological gastritis and either dietary and social habits or the presence of intestinal parasites.

[Usefulness of clinical, radiologic, and endoscopic studies in chronic diseases of the terminal ileum: analysis of 36 cases].

PubMed

Arista Nasr, J; Gamboa Domínguez, A

1992-01-01

With the purpose of defining which is the most frequent chronic pathology of the terminal ileum in a reference center (INNSZ), and establish the diagnostic accuracy of the preoperative procedures used, 36 resection specimens were reviewed histopathologically. The diseases found in decreasing frequency were: Crohn's disease, tuberculosis, carcinoids, lymphomas, endometriosis and leiomyomas. Seventy-seven percent of the cases were benign and the rest malignant. The number of cases in which the preoperative diagnosis was right or included among the differential diagnosis was as follows: clinical study 44%, radiological study 48%, endoscopical study 32% and histological study by means of endoscopic biopsy 20%. The most frequent differential diagnosis were Crohn's disease, tuberculosis and intestinal lymphoma. It is concluded that chronic disease of the ileum represents frequently a diagnostic problem due to their clinical, endoscopical and radiological similarities which may only be solved by histological analysis of the surgical specimens.

The route and timing of hydrogen sulfide therapy critically impacts intestinal recovery following ischemia and reperfusion injury.

PubMed

Jensen, Amanda R; Drucker, Natalie A; Te Winkel, Jan P; Ferkowicz, Michael J; Markel, Troy A

2018-06-01

Hydrogen sulfide (H 2 S) has many beneficial properties and may serve as a novel treatment in patients suffering from intestinal ischemia-reperfusion injury (I/R). The purpose of this study was to examine the method of delivery and timing of administration of H 2 S for intestinal therapy during ischemic injury. We hypothesized that 1) route of administration of hydrogen sulfide would impact intestinal recovery following acute mesenteric ischemia and 2) preischemic H 2 S conditioning using the optimal mode of administration as determined above would provide superior protection compared to postischemic application. Male C57BL/6J mice underwent intestinal ischemia by temporary occlusion of the superior mesenteric artery. Following ischemia, animals were treated according to one of the following (N=6 per group): intraperitoneal or intravenous injection of GYY4137 (H 2 S-releasing donor, 50mg/kg in PBS), vehicle, inhalation of oxygen only, inhalation of 80ppm hydrogen sulfide gas. Following 24-h recovery, perfusion was assessed via laser Doppler imaging, and animals were euthanized. Perfusion and histology data were assessed, and terminal ileum samples were analyzed for cytokine production following ischemia. Once the optimal route of administration was determined, preischemic conditioning with H 2 S was undertaken using that route of administration. All data were analyzed using Mann-Whitney. P-values <0.05 were significant. Mesenteric perfusion following intestinal I/R was superior in mice treated with intraperitoneal (IP) GYY4137 (IP vehicle: 25.6±6.0 vs. IP GYY4137: 79.7±15.1; p=0.02) or intravenous (IV) GYY4137 (IV vehicle: 36.3±5.9 vs. IV GYY4137: 100.7±34.0; p=0.03). This benefit was not observed with inhaled H 2 S gas (O2 vehicle: 66.6±11.4 vs. H 2 S gas: 81.8±6.0; p=0.31). However, histological architecture was only preserved with intraperitoneal administration of GYY4127 (IP vehicle: 3.4±0.4 vs. IP GYY4137: 2±0.3; p=0.02). Additionally, IP GYY4137 allowed for significant attenuation of inflammatory chemokine production of IL-6, IP-10 and MIP-2. We then analyzed whether there was a difference between pre- and postischemic administration of IP GYY4137. We found that preconditioning of animals with intraperitoneal GYY4137 only added minor improvements in outcomes compared to postischemic application. Therapeutic benefits of H 2 S are superior with intraperitoneal application of an H 2 S donor compared to other administration routes. Additionally, while intraperitoneal treatment in both the pre- and postischemic period is beneficial, preischemic application of an H 2 S donor was found to be slightly better. Further studies are needed to examine long term outcomes and further mechanisms of action prior to widespread clinical application. Basic science. N/A. Copyright © 2018 Elsevier Inc. All rights reserved.

Colic caused by Panicum maximum toxicosis in equidae in northern Brazil.

PubMed

Cerqueira, Valíria D; Riet-Correa, Gabriela; Barbosa, José D; Duarte, Marcos D; Oliveira, Carlos M C; de Oliveira, Carlos A; Tokarnia, Carlos; Lee, Stephen T; Riet-Correa, Franklin

2009-11-01

In the Amazon region of northern Brazil, Panicum maximum cultivars Mombaça, Tanzânia, and Massai cause severe colic and death in horses and mules. The disease occurs in the rainy season, when sprouting pastures are grazed by equidae. In the 8 separate disease outbreaks studied, a total of 52 out of 153 equidae were affected, including 19 that died (10 mules and 9 horses). Clinical signs were colic and abdominal dilatation, with a clinical manifestation period of 12 hr to 4 days. Serum activities of gamma-glutamyl transferase and aspartate aminotransferase were within reference intervals; however, serum urea nitrogen and creatinine concentrations were occasionally elevated. The primary gross and histologic lesions were observed in the digestive system. The stomach, small intestine, and large intestine had severe hemorrhages and occasional mucosal erosions and ulcerations. Ulceration and hemorrhage of the urinary bladder were rarely observed. Histologic examination revealed diffuse lymphoplasmacytic gastritis and enteritis with severe congestion, hemorrhage, and occasional epithelial necrosis and ulceration. Lymphocellular necrosis was occasionally observed within gut-associated lymphoid tissue. Tubular nephrosis occurred in some animals. Degeneration and occasional necrosis of bile duct epithelial cells and degeneration of hepatocytes were observed in the liver. Toxic pastures were negative for diosgenin- and yamogenin-based saponins, and oxalate concentrations were within reference intervals for the species. The toxin or toxins causing disease and the reason for the toxicity of the plant in the northern region are unknown.

Assessment of Water Quality in Asa River (Nigeria) and Its Indigenous Clarias gariepinus Fish

PubMed Central

Kolawole, Olatunji M.; Ajayi, Kolawole T.; Olayemi, Albert B.; Okoh, Anthony I.

2011-01-01

Water is a valued natural resource for the existence of all living organisms. Management of the quality of this precious resource is, therefore, of special importance. In this study river water samples were collected and analysed for physicochemical and bacteriological evaluation of pollution in the Unity Road stream segment of Asa River in Ilorin, Nigeria. Juvenile samples of Clarias gariepinus fish were also collected from the experimental Asa River and from the control Asa Dam water and were analysed for comparative histological investigations and bacterial density in the liver and intestine in order to evaluate the impact of pollution on the aquatic biota. The water pH was found to range from 6.32 to 6.43 with a mean temperature range of 24.3 to 25.8 °C. Other physicochemical parameters monitored including total suspended solids, total dissolved solids, biochemical oxygen demand and chemical oxygen demand values exceeded the recommended level for surface water quality. Results of bacteriological analyses including total heterotrophic count, total coliform and thermotolerant coliform counts revealed a high level of faecal pollution of the river. Histological investigations revealed no significant alterations in tissue structure, but a notable comparative distinction of higher bacterial density in the intestine and liver tissues of Clarias gariepinus from Asa River than in those collected from the control. It was inferred that the downstream Asa River is polluted and its aquatic biota is bacteriologically contaminated and unsafe for human and animal consumption. PMID:22163210

Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

PubMed Central

Zhou, Zhen; Meng, Qing-tao; Sun, Qian; Su, Wating; Xia, Zhengyuan; Xia, Zhong-yuan

2015-01-01

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway. Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R. Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α but decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-α and MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA. Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway. PMID:26161243

The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice.

PubMed

Campbell, Sara C; Wisniewski, Paul J; Noji, Michael; McGuinness, Lora R; Häggblom, Max M; Lightfoot, Stanley A; Joseph, Laurie B; Kerkhof, Lee J

2016-01-01

The gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet. Thirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons. Lean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp. These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host.

Effects of curcumin plus Soy oligosaccharides on intestinal flora of rats with ulcerative colitis.

PubMed

Huang, G; Ye, L; Du, G; Huang, Y; Wu, Y; Ge, S; Yang, Z; Zhu, G

2017-08-15

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P <0.01) while the contents were close to those in the SASP group. There was no statistical significance (P> 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

Remifentanil ameliorates intestinal ischemia-reperfusion injury

PubMed Central

2013-01-01

Background Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as organ transplantation, trauma and cardio-pulmonary bypass, as well as in neonatal necrotizing enterocolitis or persistent ductus arteriosus. Pharmacological protection by pretreating (“preconditioning”) with opioids attenuates IRI in a number of organs. Remifentanil appears particularly attractive for this purpose because of its ultra-short duration of action and favorable safety profile. To date, little is known about opioid preconditioning of the intestine. Methods Young adult C57BL/6J mice were randomly assigned to receive tail vein injections of 1 μg/kg of remifentanil or normal saline and underwent either ischemia-reperfusion of the intestine or a sham laparotomy. Under isoflurane anesthesia, the mice were subjected to intestinal ischemia-reperfusion by occlusion (clamping) of the superior mesenteric artery for 30 min, followed by unclamping and 60 min of reperfusion. After completion of this protocol, tissue injury and lipid peroxidation in jejunum and ileum were analyzed by histology and malondialdehyde (MDA), respectively. Systemic interleukin (IL)-6 was determined in the plasma by ELISA. Results Pretreatment with remifentanil markedly reduced intestinal IRI (P < 0.001): In the ileum, we observed a more than 8-fold decrease in injured villi (4% vs 34% in saline-pretreated animals). In fact, the mucosa in the remifentanil group was as healthy as that of sham-operated animals. This protective effect was not as pronounced in the jejunum, but the percentage of damaged villi was still reduced considerably (18% vs 42%). There was up to 3-fold more tissue MDA after intestinal ischemia-reperfusion than after sham laparotomy, but this increase in lipid peroxidation was prevented by preconditioning with remifentanil (P < 0.05). The systemic inflammatory response triggered by intestinal IRI was significantly attenuated in mice pretreated with remifentanil (159 vs 805 pg/ml of IL-6 after saline pretreatment, with 92 pg/ml in the sham groups). After sham operations, no difference was detected between the saline- and remifentanil-pretreatments in any of the parameters investigated. Conclusion Preconditioning with remifentanil attenuates intestinal IRI and the subsequent systemic inflammatory response in mice. We therefore suggest that prophylaxis with this ultra-short-acting opioid may be advantageous in various clinical scenarios of human IRI. PMID:23607370

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis1

PubMed Central

Jilling, Tamas; Simon, Dyan; Lu, Jing; Meng, Fan Jing; Li, Dan; Schy, Robert; Thomson, Richard B.; Soliman, Antoine; Arditi, Moshe; Caplan, Michael S.

2009-01-01

Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes. PMID:16920968

Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

PubMed

Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

2017-11-01

In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

Congenital Sodium Diarrhea: A Form of Intractable Diarrhea, With a Link to Inflammatory Bowel Disease.

PubMed

Janecke, Andreas R; Heinz-Erian, Peter; Müller, Thomas

2016-08-01

Congenital diarrheal disorders (CDDs) represent a group of challenging clinical conditions for pediatricians because of the severity of the presentation and the broad range of possible differential diagnoses. CDDs arise from alterations in the transport of nutrients and electrolytes across the intestinal mucosa, from enterocyte and enteroendocrine cell differentiation and/or polarization defects, and from the modulation of the intestinal immune response. Advances were made recently in deciphering the etiology and pathophysiology of one of these disorders, congenital sodium diarrhea (CSD). CSD refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. A syndromic form of CSD features choanal and intestinal atresias as well as recurrent corneal erosions. Small bowel histology frequently detects an epithelial "tufting" dysplasia. It is autosomal recessively inherited, and caused by SPINT2 mutations. The nonsyndromic form of CSD can be caused by dominant activating mutations in GUCY2C, encoding intestinal receptor guanylate cyclase C (GC-C), and by autosomal recessive SLC9A3 loss-of-function mutations. SLC9A3 encodes Na/H antiporter 3, the major intestinal brush border Na/H exchanger, and a downstream target of GC-C. A number of patients with GUCY2C and SLC9A3 mutations developed inflammatory bowel disease. Both the number of recognized CDD forms as well as the number of underlying disease genes are gradually increasing. Knowledge of these CDD genes enables noninvasive, next-generation gene panel-based testing to facilitate an early diagnosis in CDD. Primary Na/H antiporter 3 and GC-C malfunction is implicated as a predisposition for inflammatory bowel disease in subset of patients.

Regulation of intestinal immune response by selective removal of the anterior, posterior, or entire pituitary gland in Trichinella spiralis infected golden hamsters.

PubMed

Hernández-Cervantes, Rosalía; Quintanar-Stephano, Andrés; Moreno-Méndoza, Norma; López-Griego, Lorena; López-Salazar, Valeria; Hernández-Bello, Romel; Carrero, Julio César; Morales-Montor, Jorge

2013-01-01

The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms.

Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?

PubMed

Rosero, Olivér; Ónody, Péter; Kovács, Tibor; Molnár, Dávid; Fülöp, András; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2017-04-01

Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4. Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured. Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group. Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4. Copyright © 2016 Elsevier Inc. All rights reserved.

Resuscitation With 100% Oxygen Causes Intestinal Glutathione Oxidation and Reoxygenation Injury in Asphyxiated Newborn Piglets

PubMed Central

Haase, Erika; Bigam, David L.; Nakonechny, Quentin B.; Jewell, Laurence D.; Korbutt, Gregory; Cheung, Po-Yin

2004-01-01

Objective: To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen. Summary Background Data: Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury. Methods: Newborn piglets subjected to severe hypoxemia for 2 hours were resuscitated with 21%, 50%, or 100% oxygen while superior mesenteric artery (SMA) flow and hemodynamic parameters were continuously measured. Small intestinal tissue samples were analyzed for histologic injury and levels of oxidized and reduced glutathione. Results: SMA blood flow decreased to 34% and mesenteric oxygen delivery decreased to 9% in hypoxemic piglets compared with sham-operated controls. With reoxygenation, SMA blood flow increased to 177%, 157%, and 145% of baseline values in piglets resuscitated with 21%, 50%, and 100% oxygen, respectively. Mesenteric oxygen delivery increased to more than 150% of baseline values in piglets resuscitated with 50% or 100% oxygen, and this correlated significantly with the degree of oxidative stress, as measured by the oxidized-to-reduced glutathione ratio. Two of eight piglets resuscitated with 100% oxygen developed gross and microscopic evidence of pneumatosis intestinalis and severe mucosal injury, while all other piglets were grossly normal. Conclusions: Resuscitation of hypoxemic newborn piglets with 100% oxygen is associated with an increase in oxygen delivery and oxidative stress, and may be associated with the development of small intestinal hypoxia-reoxygenation injury. Resuscitation of asphyxiated newborns with lower oxygen concentrations may help to decrease the risk of necrotizing enterocolitis. PMID:15273563

Influence of Technological Treatments on the Functionality of Bifidobacterium lactis INL1, a Breast Milk-Derived Probiotic.

PubMed

Zacarías, María Florencia; Souza, Tassia Costa; Zaburlín, Natalia; Carmona Cara, Denise; Reinheimer, Jorge; Nicoli, Jacques; Vinderola, Gabriel

2017-10-01

The aim of this study is to evaluate the influence of the technological processing on the functionality of the human breast milk probiotic strain Bifidobacterium lactis INL1. In vitro antagonistic activity of B. lactis INL1 was detected for Gram-positive and Gram-negative pathogens. B. lactis INL1 was administered to mice as fresh (F), frozen (Z), spray-dried (S), or lyophilized (L) culture. Immune parameters (IgA, IL-10, and IFN-γ) were determined and histological analysis was performed to assess functionality and protection capacity against Salmonella. In BALB/c mice, F and S cultures induced an increase in the number of IgA-producing cells in the small intestine and IL-10 levels were increased for L culture in the large intestine. In Swiss mice, B. lactis INL1 increased secretory-IgA levels in the small intestine before and after Salmonella infection, both as F or dehydrated culture. Also, an attenuation of damage in the intestinal epithelium and less inflammatory infiltrates were observed in animals that received F and S cultures, whereas in liver only F showed some effect. The anti-inflammatory effect was confirmed in both tissues by myeloperoxidase activity and by IFN-γ levels in the intestinal content. B. lactis INL1 showed inhibitory activity against pathogens and confirmed its probiotic potential in animal models. Technological processing of the probiotic strain affected its functionality. This work provides evidence about the influence of technology on the functionality of probiotics, which may help probiotics and functional food manufacturers to take processing into consideration when assessing the functionality of new strains. © 2017 Institute of Food Technologists®.

Effect of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin complex on indomethacin-induced small intestinal injury in mice.

PubMed

Ishida, Tsukasa; Miki, Ikuya; Tanahashi, Toshihito; Yagi, Saori; Kondo, Yasuyuki; Inoue, Jun; Kawauchi, Shoji; Nishiumi, Sin; Yoshida, Masaru; Maeda, Hideko; Tode, Chisato; Takeuchi, Atsuko; Nakayama, Hirokazu; Azuma, Takeshi; Mizuno, Shigeto

2013-08-15

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury is a serious clinical event with recent advances of diagnostic technologies, but a successful therapeutic method to treat such injuries is still lacking. Licorice, a traditional herbal medicine, and its derivatives have been widely used for the treatment of a variety of diseases due to their extensive biological actions. However, it is unknown whether these derivatives have an effect on NSAIDs-induced small intestinal damage. Previously, the anti-inflammatory effects of three compounds extracted from the licorice root, glycyrrhizin, 18β-glycyrrhetinic acid, and dipotassium glycyrrhizinate, were compared in vitro cell culture. The most prominent inhibitory effect on the tumor necrosis factor-α (TNF-α) production was observed with the administration of 18β-glycyrrhetinic acid as an active metabolite of glycyrrhizin. In this study, a complex compound of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin was examined to improve the oral bioavailability. After administration of this complex to indomethacin treated mice, a significantly high plasma concentration of 18β-glycyrrhetinic acid was detected using the tandem mass spectrometry coupled with the HPLC. Furthermore, the complex form of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin reduced mRNA expressions of TNF-α, interleukin (IL)-1β, and IL-6, which was histologically confirmed in the improvement of indomethacin-induced small intestinal damage. These results suggest that the complex of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin has the potential therapeutic value for preventing the adverse effects of indomethacin-induced small intestinal injury. Copyright © 2013 Elsevier B.V. All rights reserved.

Protective Effect of Lactobacillus casei Strain Shirota on Shiga Toxin-Producing Escherichia coli O157:H7 Infection in Infant Rabbits

PubMed Central

Ogawa, Michinaga; Shimizu, Kensuke; Nomoto, Koji; Takahashi, Masatoshi; Watanuki, Masaaki; Tanaka, Ryuichiro; Tanaka, Tetsuya; Hamabata, Takashi; Yamasaki, Shinji; Takeda, Yoshifumi

2001-01-01

We examined colonization patterns of Shiga toxin-producing Escherichia coli (STEC), concentrations of Shiga toxins (Stxs) and specific immunoglobulin A (lgA) against Stxs and STEC bacterial cell surface antigen in various portions of the gastrointestinal tract in an infant rabbit infection model. After inoculation of 3-day-old infant rabbits with STEC strain 89020087 at low doses (∼103 CFU/body), numbers of colonizing STEC bacteria and concentrations of Stxs in the intestine increased dramatically and the animals developed diarrhea within a couple of days after infection. Daily administration of Lactobacillus casei from the day of birth dramatically decreased the severity of diarrhea and lowered STEC colonization levels in the gastrointestinal tract 100-fold day 7 after infection. Both Stx1 and Stx2 concentrations in the intestines and histological damage to the intestinal mucus induced by STEC infection were decreased by the administration of L. casei. Examination of the concentrations of volatile fatty acids and pH of the intestinal contents revealed that the protective effect of L. casei administration against STEC infection was not due to fermented products such as lactic acid in the gastrointestinal tract. Administration of L. casei increased levels of lgAs against Stx1, Stx2, and formalin-killed STEC cells in the colon approximately two-, four-, and threefold, respectively, compared with those of the untreated controls by day 7 after infection. These results suggest that administration of L. casei strain Shirota enhances the local immune responses to STEC cells and Stxs and leads to elimination of STEC and thus decreases Stx concentrations in the intestines. PMID:11160007

Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

NASA Astrophysics Data System (ADS)

Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

2016-10-01

The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

Evaluation of gastric histology in children and adolescents with Helicobacter pylori gastritis using the Update Sydney System.

PubMed

Langner, Marini; Machado, Rodrigo Strehl; Patrício, Francy R S; Kawakami, Elisabete

2009-01-01

Although Helicobacter pylori infection is prevalent in our country, there are few studies evaluating the associated histological abnormalities in children. To evaluate the histological features of the gastric mucosa in children and adolescents with Helicobacter pylori gastritis. One hundred and thirty two gastric biopsies from 22 symptomatic patients infected with H. pylori (14F/8M, median age 10 y 5 mo, age range 2 y 11 mo to 16 y 9 mo) were evaluated. Evaluated gastric regions included: antrum (lesser and greater curvature), corpus (lesser and greater curvature), incisura angularis and fundus. Histological examination was performed according to the Updated Sydney System, and regional scores for polymorphonuclear and mononuclear cell infiltrate as well as bacterial density were generated. Fifteen (68.2%) patients presented H. pylori-chronic active gastritis, six (27.3%) presented antrum-predominant H. pylori-chronic active gastritis, and one (4.5%) presented corpus-predominant H. pylori-chronic active gastritis. Polymorphonuclear cell infiltrate and mononuclear cell infiltrate were observed in 93.9% and 98.5% of the biopsy specimens, respectively. Higher histological scores for polymorphonuclear infiltrate, mononuclear infiltrate, and bacterial density were observed in the gastric antrum. Intestinal metaplasia and gastric atrophy were not identified in any patient. Lymphoid aggregates and lymphoid follicles were observed in the gastric antrum of three (13.6%) and seven (31.8%) patients, respectively, but they were not related to antral nodularity. Chronic active gastritis was observed in all patients with H. pylori infection. However, antral or corporeal predominance was not observed in most patients.

Use of knowledge-sharing web-based portal in gross and microscopic anatomy.

PubMed

Durosaro, Olayemi; Lachman, Nirusha; Pawlina, Wojciech

2008-12-01

Changes in worldwide healthcare delivery require review of current medical school curricula structure to develop learning outcomes that ensures mastery of knowledge and clinical competency. In the last 3 years, Mayo Medical School implemented outcomes-based curriculum to encompass new graduate outcomes. Standard courses were replaced by 6-week clinically-integrated didactic blocks separated by student-self selected academic enrichment activities. Gross and microscopic anatomy was integrated with radiology and genetics respectively. Laboratory components include virtual microscopy and anatomical dissection. Students assigned to teams utilise computer portals to share learning experiences. High-resolution computed tomographic (CT) scans of cadavers prior to dissection were made available for correlative learning between the cadaveric material and radiologic images. Students work in teams on assigned presentations that include histology, cell and molecular biology, genetics and genomic using the Nexus Portal, based on DrupalEd, to share their observations, reflections and dissection findings. New generation of medical students are clearly comfortable utilising web-based programmes that maximise their learning potential of conceptually difficult and labor intensive courses. Team-based learning approach emphasising the use of knowledge-sharing computer portals maximises opportunities for students to master their knowledge and improve cognitive skills to ensure clinical competency.

[Effects of cromolyn sodium on intestinal ischemia-reperfusion injury by inhibiting PAR-2 expression in rats].

PubMed

Liu, De-zhao; Chen, Zhong-gang; Ge, Mian; Gan, Xiao-liang; Hei, Zi-qing

2012-10-09

To explore the effects of cromolyn sodium (CS) on intestinal ischemia-reperfusion (IIR) and its relationship with mast cell activation and protease-activated receptor 2 (PAR-2) expression. A total of 32 SD rats were randomly divided into 4 groups: sham-operated (S), intestinal ischemia reperfusion (IIR), CS (a mast cell stabilizer, CS, 25 mg/kg) and compound 48/80 (a mast cell degranulation, CP, 0.75 mg/kg) (n = 8 each). IIR was induced by clamping superior mesenteric artery for 75 min followed by reperfusion for 3 hours. The above agents were intravenously administrated at 5 min pre-reperfusion. Rats were then sacrificed and intestinal issues harvested for histological examinations. The tryptase expression and mast cell count were analyzed by immunohistochemistry. PAR-2 was analyzed by Western blot. The Chiu's score (0.75 ± 0.21), mast cell count (10 ± 3), tryptase expression (125 ± 15) and PAR-2 expression (109 ± 10) of group S were the least while those of group CP the most (all P < 0.05). The Chiu's score (2.14 ± 0.64), mast cell count (15 ± 4), tryptase expression (138 ± 17) and PAR-2 expression (124 ± 12) of group CS were less than those of groups IIR and CP (all P < 0.05). Cromolyn sodium may reduce IIR injury by stabilizing mast cell membrane and inhibiting the expressions of tryptase and PAR-2.

[Active search of celiac disease among first degree relatives of known celiac patients].

PubMed

Bejares, Marcela; Oyarzún, Amaya; Lucero, Yalda; Espinoza, Nelly; Bascuñán, Karla; Araya, Magdalena

2015-12-01

Active search of celiac disease (CD) among risk groups has significantly increased the scope of known clinical variants. To measure the frequency and clinical characteristics of CD among first degree relatives (FDR) of known celiac cases. Between January 2012-August 2013, 37 patients with celiac disease brought 113 FDR for assessment. Their clinical data was recorded and a blood sample was obtained to measure serum Immunoglobulin A (IgA) levels, anti-transglutaminase (tTG) and anti-endomisial (EMA) antibodies. Cases with positive serology were advised to have an intestinal biopsy. Fourteen relatives (12.4%) had positive serological results and none had IgA deficiency. Among IgA-tTG (-) cases, measurement of IgA/IgG-tTG identified an additional case. Two of the 14 relatives were EMA positive. All 14 cases were advised to have an intestinal biopsy, but only 6 accepted the procedure. In two, the intestinal lesion was classified Marsh ≥ 2 and active CD was diagnosed. Histology in the remaining four was Marsh 0/1 and were diagnosed potential CD, remaining under control, without gluten free diet. Serological prevalence of CD among first degree relatives of known celiac cases was 15 fold greater than in THE general Chilean population, strongly supporting the idea of implementing active search to customary clinical practice. Determination of IgA/IgG-tTG may be useful to improve the yield of active search. Intestinal biopsies were crucial to differentiate active classic CD from potential CD.

Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.

PubMed

O'Connell, Amy E; Zhou, Fanny; Shah, Manasvi S; Murphy, Quinn; Rickner, Hannah; Kelsen, Judith; Boyle, John; Doyle, Jefferson J; Gangwani, Bharti; Thiagarajah, Jay R; Kamin, Daniel S; Goldsmith, Jeffrey D; Richmond, Camilla; Breault, David T; Agrawal, Pankaj B

2018-06-04

Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs). The enteroids generated from WNT2B-deficient intestinal epithelium could not be expanded and did not survive passage. Addition of CHIR-99021 (a GSK3A and GSK3B inhibitor and activator of canonical WNT/β-CATENIN signaling) could not rescue WNT2B-deficient enteroids. Addition of supplemental recombinant murine WNT2B was able to perpetuate small enteroids for multiple passages but failed to expand their number. Enteroids showed a 10-fold increase in the expression of LEF1 mRNA and a 100-fold reduction in TLR4 expression, compared with controls by quantitative RT-PCR, indicating alterations in canonical WNT and microbial pattern-recognition signaling. In summary, individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation associated with decreased ISC number and function, likely explaining their diarrheal phenotype. WNT2B deficiency should be considered for individuals with neonatal-onset diarrhea. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Photoacoustic imaging of intestinal strictures: microscopic and macroscopic assessment in vivo (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Lei, Hao; Johnson, Laura A.; Moons, David S.; Ma, Teng; Zhou, Qifa; Rice, Michael D.; Ni, Jun; Wang, Xueding; Higgins, Peter D. R.

2017-03-01

The pathology of Crohn's disease (CD) is characterized by obstructing intestinal strictures because of inflammation (with high levels of hemoglobin), fibrosis (high levels of collagen), or a combination of both. Inflammatory strictures are medically treated. Fibrotic strictures have to be removed surgically. The accurate characterization of the strictures is therefore critical for the management of CD. Currently the comprehensive assessment of a stricture is difficult, as the standard diagnostic procedure, endoscopic biopsy, is superficial and with limited locations as well as depth. In our previous studies, photoacoustic imaging (PAI) has recovered the layered architectures and the relative content of the molecular components in human and animal tissues ex vivo. This study will investigate the capability of multispectral PAI in resolving the architecture and the molecular components of intestinal strictures in rats in vivo. PA images at 532, 1210 and 1310 nm targeting the strong optical absorption of hemoglobin, lipid and collagen were acquired using two approaches. A compact linear array, CL15-7, was used to transcutaneously acquire PA signals generated by the a fiber optics diffuser positioned within the inner lumen of the strictures. Another approach was to use an endoscopic capsule probe for acoustic resolution PA microscopy. The capsule probe is designed for human and therefore cannot fit into rat colon. The inner surface of the intestinal stricture was exposed and the probe was attached to the diseased location for imaging. The findings in PA images were confirmed by histology results.

Segmental dilatation of the intestine.

PubMed

Ben Brahim, Mohamed; Belghith, Mohsen; Mekki, Mongi; Jouini, Riadh; Sahnoun, Lassaad; Maazoun, Kaies; Krichene, Imed; Golli, Mondher; Monastiri, Kamel; Nouri, Abdellatif

2006-06-01

The aim of this work is to discuss the pathogenesis of the segmental dilatation of the intestine (SDI) and to review its clinical presentation and the ways to confirm the diagnosis. Eight cases of pathologically proven SDI from 1987 to 2003 were reviewed and discussed. There were 7 newborns and a 1-year-old boy. Our patients are 5 boys and 3 girls. In all cases, the diagnosis was not suspected before surgery. Two patients presented with a low neonatal bowel obstruction. Six patients were operated for omphalocele, which was the most frequent associated malformation. The SDI involved the ileum in all patients. The treatment consisted on a resection of the dilated segment with an end-to-end anastomosis. Histological examination demonstrated the presence of ganglion cells in all cases. The muscular layer was hypertrophied in two cases and very thin in one case. A heterotopic gastric mucosa was observed in one case. No anomalies were observed in 5 cases. The postoperative course was uneventful in 6 cases with a mean follow-up of 5 years. Segmental intestinal dilatation is an exceptional pathology with an unknown etiology and a misleading clinical presentation. Several theories were proposed to explain this malformation; however, most authors are rather inclined to an embryological theory incriminating an extrinsic intrauterine intestinal compression. Most cases are neonatal discoveries. The clinical polymorphism and the lack of specificity of radiological investigations explain the difficulties to have a preoperative diagnosis. However, this difficulty is compensated by the favorable evolution after the resection of the dilated segment.

Serum calprotectin levels correlate with biochemical and histological markers of disease activity in TNBS colitis

PubMed Central

Cury, Didia Bismara; Mizsputen, Sender Jankiel; Versolato, Clara; Miiji, Luciana Odashiro; Pereira, Edson; Delboni, Maria Aparecida; Schor, Nestor; Moss, Alan C.

2014-01-01

Background and aim Serum calprotectin is elevated in patients with inflammatory bowel disease (IBD). Whether it correlates other markers of disease activity is unknown. The aim of this study was to correlate serum calprotectin with biochemical and histological measures of intestinal inflammation. Materials and methods TNBS colitis was induced in wistar rats, and serial blood samples were collected at 0, 3, and 12 days. Animals were subsequently sacrificed for pathological evaluation at day 12. Serum calprotectin and cytokines were measured by ELISA. Pathologic changes were classified at the macroscopic and microscopic levels. Results TNBS colitis induced elevated serum calprotectin, TNF and IL-6 within 24 h. Levels of serum calprotectin remained elevated in parallel to persistence of loose stool and weight loss to day 12. Serum calprotectin levels correlated with serum levels of TNF-α and IL6 (p < 0.001), but not CRP. Animals with liquid stool had significantly higher levels of serum calprotectin than control animals. There was a correlation between macroscopic colitis scores, and levels of serum calprotectin. Conclusion Serum calprotectin levels correlate with biochemical and histological markers of inflammation in TNBS colitis. This biomarker may have potential for diagnostic use in patients with IBD. PMID:23685388

Human Ghrelin Mitigates Intestinal Injury and Mortality after Whole Body Irradiation in Rats

PubMed Central

Wang, Zhimin; Yang, Weng Lang; Jacob, Asha; Aziz, Monowar; Wang, Ping

2015-01-01

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI and survival outcome was examined. The 10 Gy WBI produced a LD70/30 model in SD rats (30% survival in 30 days). The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury. PMID:25671547

Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats.

PubMed

Wang, Zhimin; Yang, Weng Lang; Jacob, Asha; Aziz, Monowar; Wang, Ping

2015-01-01

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI and survival outcome was examined. The 10 Gy WBI produced a LD70/30 model in SD rats (30% survival in 30 days). The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins

PubMed Central

Wang, Lyu; Cui, Yun-Liang; Zhang, Zhe; Lin, Zhao-Fen; Chen, De-Chang

2017-01-01

Background: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. Methods: Healthy male Sprague-Dawley rats (weighing 230–250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured. Results: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001), and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P < 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P < 0.001), D (0.029 ± 0.003, P < 0.001), E (0.026 ± 0.003, P < 0.001), F (0.027 ± 0.003, P < 0.001), G (0.030 ± 0.005, P < 0.001), and H (0.026 ± 0.002, P < 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05). Conclusion: Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins. PMID:28485323

Histopathology of yearling sockeye salmon (Oncorhynchus nerka) infected with infectious hematopoietic necrosis (IHN)

USGS Publications Warehouse

1979-01-01

Infectious hematopoietic necrosis (IHN) is generally believed to be a virus disease of very young salmonids. In recent years there have been increasing numbers of unpublished reports that this disease has been occurring uncharacteristically in fish as old as 7-14 months. Sockeye salmon (Oncorhynchus nerka) of this age the histological changes were not severe. Intestinal tract granular cells thought to be pathognomic in young fish were conspicuously absent. Kidney imprints showed necrobiotic bodies however, and subtle changes were observed in the spleen and kidney hematopoietic tissue.

Effects of the oral administration of the exopolysaccharide produced by Lactobacillus kefiranofaciens on the gut mucosal immunity.

PubMed

Vinderola, Gabriel; Perdigón, Gabriela; Duarte, Jairo; Farnworth, Edward; Matar, Chantal

2006-12-01

The probiotic effects ascribed to lactic acid bacteria (LAB) and their fermented dairy products arise not only from whole microorganisms and cell wall components but also from peptides and extracellular polysaccharides (exopolysaccharides) produced during the fermentation of milk. There is a lack of knowledge concerning the immune mechanisms induced by exopolysaccharides produced by lactic acid bacteria, which would allow a better understanding of the functional effects described to them. The aim of this study was to investigate the in vivo immunomodulating capacity of the exopolysaccharide produced by Lactobacillus kefiranofaciens by analyzing the profile of cytokines and immunoglobulins induced at the intestinal mucosa level, in the intestinal fluid and blood serum. BALB/c mice received the exopolysaccharide produced by L. kefiranofaciens for 2, 5 or 7 consecutive days. At the end of each period of administration, control and treated mice were sacrificed and the numbers of IgA+ and IgG+ cells were determined on histological slices of the small and large intestine by immunofluorescence. Cytokines (IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha) were also determined in the gut lamina propria as well as in the intestinal fluid and blood serum. There was an increase of IgA+ cells in the small and large intestine lamina propria, without change in the number of IgG+ cells in the small intestine. This study reports the effects of the oral administration of the exopolysaccharide produced by L. kefiranofaciens in the number of IgA+ cells in the small and large intestine, comparing simultaneously the production of cytokines by cells of the lamina propria and in the intestinal fluid and blood serum. The increase in the number of IgA+ cells was not simultaneously accompanied by an enhance of the number of IL-4+ cells in the small intestine. This finding would be in accordance with the fact that, in general, polysaccharide antigens elicit a T-independent immune response. For IL-10+, IL-6+ and IL-12+ cells, the values found were slightly increased compared to control values, while IFNgamma+ and TNFalpha+ cells did not change compared to control values. The effects observed on immunoglobulins and in all the cytokines assayed in the large intestine after kefiran administration were of greater magnitude than the ones observed in the small intestine lamina propria, which may be due to the saccharolytic action of the colonic microflora. In the intestinal fluid, only IL-4 and IL-12 increased compared to control values. In blood serum, all the cytokines assayed followed a pattern of production quite similar to the one found for them in the small intestine lamina propria. We observed that the exopolysaccharide induced a gut mucosal response and it was able to up and down regulate it for protective immunity, maintaining intestinal homeostasis, enhancing the IgA production at both the small and large intestine level and influencing the systemic immunity through the cytokines released to the circulating blood.

Analyses of clinical, pathological and virological features of human rotavirus strain, YO induced gastroenteritis in infant BALB/c mice.

PubMed

Buragohain, Manika; Dhale, Ganesh S; Raut, Chandrashekhar G; Kang, Gagandeep; Chitambar, Shobha D

2011-04-01

Experimental studies of human rotavirus infections in mice are limited and there is lack of information on the quantitative assessment of rotaviral replication and its relationship with histological changes. In the present study, consequences of human rotavirus strain, YO induced gastroenteritis in infant BALB/c mice were analyzed for the occurrence of clinical symptoms, histopathology and virological events. The infected animals developed diarrhea and dehydration and showed accumulation of vacuolated enterocytes with lodging of the rotavirus antigens and shortening of villi in the intestine over a period of 5 days. The ileum was identified as the most susceptible and supportive part of small intestine for perpetuation of rotavirus infection in mice. Rotaviral antigen/RNA in stool and RNA in intestine were detected throughout the clinical disease period. At 48-72 h post inoculation, diarrhea was at the peak (90-95%) in the infected animals with increased load of viral RNA and intense pathological lesions suggesting it as the critical time point in the course of infection. The rising titers of antirotavirus neutralizing antibodies ascertained the replication of human rotavirus strain, YO in mice. These data may contribute to the understanding of pathophysiological, immunological and virological characteristics of rotavirus infections in mice. Copyright © 2010. Published by Elsevier SAS.

Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

PubMed Central

Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

2010-01-01

Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

Platynosomum fastosum-induced chronic intrahepatic cholangitis and Spirometra spp. infections in feral cats from Grand Cayman.

PubMed

Headley, S A; Gillen, M A; Sanches, A W D; Satti, M Z

2012-06-01

The occurrence of platynosomiasis and intestinal sparganosis is described in feral cats from Grand Cayman, Cayman Islands. Spirometra spp. was observed within the intestine of 18.18% (10/55) of cats; 1.18% (1/55) of cats demonstrated gross and histological manifestation of parasitism by Platynosomum fastosum, but 14.5% (8/55) of cats had the characteristic pathological manifestations of P. fastosum-induced intrahepatic cholangitis without the concomitant presence of the intraductal trematode. Combined parasitism (Spirometra spp. and P. fastosum) was observed in 9.09% (5/55) of feral cats. Significant pathological findings were only associated with the hepatic fluke, P. fastosum, and were grossly characterized by moderate hepatomegaly with enlarged and dilated bile ducts. Examples of cestodes with morphological features characteristic of Spirometra spp. were observed within the small intestine without any associated pathological lesion. The histopathological evaluation of liver fragments revealed chronic intrahepatic cholangitis with and without the associated intraductal trematode, and was characterized by marked periductal fibrosis, adenomatous proliferation of bile duct epithelium, dilation of intrahepatic bile ducts and portal accumulations of inflammatory cells. The occurrence of the cestode in feral cats coupled with factors that are unique to Grand Cayman makes this island the ideal location for sporadic cases of human sparganosis.

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis.

PubMed

Nilsson, Anna; Peric, Alexandra; Strimfors, Marie; Goodwin, Richard J A; Hayes, Martin A; Andrén, Per E; Hilgendorf, Constanze

2017-07-25

Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

Scalability of an endoluminal spring for distraction enterogenesis.

PubMed

Rouch, Joshua D; Huynh, Nhan; Scott, Andrew; Chiang, Elvin; Wu, Benjamin M; Shekherdimian, Shant; Dunn, James C Y

2016-12-01

Techniques of distraction enterogenesis have been explored to provide increased intestinal length to treat short bowel syndrome (SBS). Self-expanding, polycaprolactone (PCL) springs have been shown to lengthen bowel in small animal models. Their feasibility in larger animal models is a critical step before clinical use. Juvenile mini-Yucatan pigs underwent jejunal isolation or blind ending Roux-en-y jejunojejunostomy with insertion of either a PCL spring or a sham PCL tube. Extrapolated from our spring characteristics in rodents, proportional increases in spring constant and size were made for porcine intestine. Jejunal segments with 7mm springs with k between 9 and 15N/m demonstrated significantly increased lengthening in isolated segment and Roux-en-y models. Complications were noted in only two animals, both using high spring constant k>17N/m. Histologically, lengthened segments in the isolated and Roux models demonstrated significantly increased muscularis thickness and crypt depth. Restoration of lengthened, isolated segments back into continuity was technically feasible after 6weeks. Self-expanding, endoluminal PCL springs, which exert up to 0.6N force, safely achieve significant intestinal lengthening in a translatable, large-animal model. These spring characteristics may provide a scalable model for the treatment of SBS in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrasonographic thickening of the muscularis propria in feline small intestinal small cell T-cell lymphoma and inflammatory bowel disease

PubMed Central

Daniaux, Lise A; Laurenson, Michele P; Marks, Stanley L; Moore, Peter F; Taylor, Sandra L; Chen, Rachel X; Zwingenberger, Allison L

2014-01-01

Gastrointestinal lymphoma is the most common form of lymphoma in the cat. More recently, an ultrasonographic pattern associated with feline small cell T-cell gastrointestinal lymphoma has been recognized as a diffuse thickening of the muscularis propria of the small intestine. This pattern is also described with feline inflammatory bowel disease. To evaluate the similarities between the diseases, we quantified the thickness of the muscularis propria layer in the duodenum, jejunum and ileum of 14 cats affected by small cell T-cell lymphoma and inflammatory bowel disease (IBD) and 19 healthy cats. We found a significantly increased thickness of the muscularis propria in cats with lymphoma and IBD compared with healthy cats. The mean thickness of the muscularis propria in cats with lymphoma or IBD was twice the thickness than that of healthy cats, and was the major contributor to significant overall bowel wall thickening in the duodenum and jejunum. A muscularis to submucosa ratio >1 is indicative of an abnormal bowel segment. Colic lymph nodes in cats with lymphoma were increased in size compared with healthy cats. In cats with gastrointestinal lymphoma and histologic transmural infiltration of the small intestines, colic or jejunal lymph nodes were rounded, increased in size and hypoechoic. PMID:23900499

Morphological and functional changes after benzalkonium chloride treatment of the small intestinal Thiry-Vella loop in rats.

PubMed

Móricz, K; Gyetvai, B; Bárdos, G

1998-08-01

The aim of this work was to study the effects of benzalkonium chloride (BAC) treatment on the small intestine and its functioning in rats surgically prepared with Thiry-Vella intestinal loop. The loops were treated with either BAC, which ablated much of the myenteric plexus and extrinsic innervation, or with physiological saline (SAL). In vivo drinking experiments were performed to examine the effect on fluid intake and behavioral indices of distending the loop with a balloon. Spontaneous motility and its changes induced by acetylcholine (ACh) and histamine (His) were studied on isolated stripes in vitro. Finally, samples from the loops were examined histologically. Though reduction of the cell number was less than expected and no differences of the thickness of the muscular layer between the two groups was observed, BAC treatment altered the pattern of spontaneous activity and also the sensitivity to ACh and His in isolated stripes. In vivo distension of the SAL-treated loops reduced fluid intake and produced signs of aversivity; these effects were absent in the BAC-treated group. Our results show that despite the differences in the degree of ablation from those obtained by others, BAC treatment can be used to study the mechanisms underlying the effects of the enteral stimuli on the behavior.

Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism.

PubMed

Korecka, Agata; Dona, Anthony; Lahiri, Shawon; Tett, Adrian James; Al-Asmakh, Maha; Braniste, Viorica; D'Arienzo, Rossana; Abbaspour, Afrouz; Reichardt, Nicole; Fujii-Kuriyama, Yoshiaki; Rafter, Joseph; Narbad, Arjan; Holmes, Elaine; Nicholson, Jeremy; Arulampalam, Velmurugesan; Pettersson, Sven

2016-01-01

The ligand-induced transcription factor, aryl hydrocarbon receptor (AhR) is known for its capacity to tune adaptive immunity and xenobiotic metabolism-biological properties subject to regulation by the indigenous microbiome. The objective of this study was to probe the postulated microbiome-AhR crosstalk and whether such an axis could influence metabolic homeostasis of the host. Utilising a systems-biology approach combining in-depth 1 H-NMR-based metabonomics (plasma, liver and skeletal muscle) with microbiome profiling (small intestine, colon and faeces) of AhR knockout (AhR -/- ) and wild-type (AhR +/+ ) mice, we assessed AhR function in host metabolism. Microbiome metabolites such as short-chain fatty acids were found to regulate AhR and its target genes in liver and intestine. The AhR signalling pathway, in turn, was able to influence microbiome composition in the small intestine as evident from microbiota profiling of the AhR +/+ and AhR -/- mice fed with diet enriched with a specific AhR ligand or diet depleted of any known AhR ligands. The AhR -/- mice also displayed increased levels of corticosterol and alanine in serum. In addition, activation of gluconeogenic genes in the AhR -/- mice was indicative of on-going metabolic stress. Reduced levels of ketone bodies and reduced expression of genes involved in fatty acid metabolism in the liver further underscored this observation. Interestingly, exposing AhR -/- mice to a high-fat diet showed resilience to glucose intolerance. Our data suggest the existence of a bidirectional AhR-microbiome axis, which influences host metabolic pathways.

Contribution of acetate to butyrate formation by human faecal bacteria.

PubMed

Duncan, Sylvia H; Holtrop, Grietje; Lobley, Gerald E; Calder, A Graham; Stewart, Colin S; Flint, Harry J

2004-06-01

Acetate is normally regarded as an endproduct of anaerobic fermentation, but butyrate-producing bacteria found in the human colon can be net utilisers of acetate. The butyrate formed provides a fuel for epithelial cells of the large intestine and influences colonic health. [1-(13)C]Acetate was used to investigate the contribution of exogenous acetate to butyrate formation. Faecalibacterium prausnitzii and Roseburia spp. grown in the presence of 60 mm-acetate and 10 mm-glucose derived 85-90 % butyrate-C from external acetate. This was due to rapid interchange between extracellular acetate and intracellular acetyl-CoA, plus net acetate uptake. In contrast, a Coprococcus-related strain that is a net acetate producer derived only 28 % butyrate-C from external acetate. Different carbohydrate-derived energy sources affected butyrate formation by mixed human faecal bacteria growing in continuous or batch cultures. The ranking order of butyrate production rates was amylopectin > oat xylan > shredded wheat > inulin > pectin (continuous cultures), and inulin > amylopectin > oat xylan > shredded wheat > pectin (batch cultures). The contribution of external acetate to butyrate formation in these experiments ranged from 56 (pectin) to 90 % (xylan) in continuous cultures, and from 72 to 91 % in the batch cultures. This is consistent with a major role for bacteria related to F. prausnitzii and Roseburia spp. in butyrate formation from a range of substrates that are fermented in the large intestine. Variations in the dominant metabolic type of butyrate producer between individuals or with variations in diet are not ruled out, however, and could influence butyrate supply in the large intestine.

Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests

PubMed Central

2013-01-01

Background Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. Methods We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. Results Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. Conclusions Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved. PMID:23347408

Glucose Plus Fructose Ingestion for Post-Exercise Recovery-Greater than the Sum of Its Parts?

PubMed

Gonzalez, Javier T; Fuchs, Cas J; Betts, James A; van Loon, Luc J C

2017-03-30

Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose-fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption. Moreover, the addition of glucose to fructose ingestion facilitates intestinal fructose absorption via a currently unidentified mechanism. The co-ingestion of glucose and fructose therefore provides faster rates of carbohydrate absorption than the sum of glucose and fructose absorption rates alone. Similar metabolic effects can be achieved via the ingestion of sucrose (a disaccharide of glucose and fructose) because intestinal absorption is unlikely to be limited by sucrose hydrolysis. Carbohydrate ingestion at a rate of ≥1.2 g carbohydrate per kg body mass per hour appears to maximise post-exercise muscle glycogen repletion rates. Providing these carbohydrates in the form of glucose-fructose (sucrose) mixtures does not further enhance muscle glycogen repletion rates over glucose (polymer) ingestion alone. In contrast, liver glycogen repletion rates are approximately doubled with ingestion of glucose-fructose (sucrose) mixtures over isocaloric ingestion of glucose (polymers) alone. Furthermore, glucose plus fructose (sucrose) ingestion alleviates gastrointestinal distress when the ingestion rate approaches or exceeds the capacity for intestinal glucose absorption (~1.2 g/min). Accordingly, when rapid recovery of endogenous glycogen stores is a priority, ingesting glucose-fructose mixtures (or sucrose) at a rate of ≥1.2 g·kg body mass -1 ·h -1 can enhance glycogen repletion rates whilst also minimising gastrointestinal distress.

Glucose Plus Fructose Ingestion for Post-Exercise Recovery—Greater than the Sum of Its Parts?

PubMed Central

Gonzalez, Javier T.; Fuchs, Cas J.; Betts, James A.; van Loon, Luc J. C.

2017-01-01

Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose–fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption. Moreover, the addition of glucose to fructose ingestion facilitates intestinal fructose absorption via a currently unidentified mechanism. The co-ingestion of glucose and fructose therefore provides faster rates of carbohydrate absorption than the sum of glucose and fructose absorption rates alone. Similar metabolic effects can be achieved via the ingestion of sucrose (a disaccharide of glucose and fructose) because intestinal absorption is unlikely to be limited by sucrose hydrolysis. Carbohydrate ingestion at a rate of ≥1.2 g carbohydrate per kg body mass per hour appears to maximise post-exercise muscle glycogen repletion rates. Providing these carbohydrates in the form of glucose–fructose (sucrose) mixtures does not further enhance muscle glycogen repletion rates over glucose (polymer) ingestion alone. In contrast, liver glycogen repletion rates are approximately doubled with ingestion of glucose–fructose (sucrose) mixtures over isocaloric ingestion of glucose (polymers) alone. Furthermore, glucose plus fructose (sucrose) ingestion alleviates gastrointestinal distress when the ingestion rate approaches or exceeds the capacity for intestinal glucose absorption (~1.2 g/min). Accordingly, when rapid recovery of endogenous glycogen stores is a priority, ingesting glucose–fructose mixtures (or sucrose) at a rate of ≥1.2 g·kg body mass−1·h−1 can enhance glycogen repletion rates whilst also minimising gastrointestinal distress. PMID:28358334

Pregnancy-associated Sweet's syndrome in an acute episode of ulcerative colitis.

PubMed

Best, J; Dechene, A; Esser, S; Gerken, G; Canbay, A

2009-08-01

A 33-year old pregnant patient (pregnancy week 15) with a past medical history of ulcerative colitis with onset of the disease following the birth of her first child was admitted to the hospital with symptoms of weight loss, pyrexia, leukocytosis and bloody and mucous diarrhoea. Total ileocolonoscopy revealed an acute flare of ulcerative colitis. Within a few days, tender erythematous skin lesions occurred and were histologically proven to be neutrophilic dermatosis. Treatment with highly-dosed prednisone led to a complete remission of both cutaneous and intestinal manifestations. Both pathogenic entities are associated with similar immunological alterations, such as comparable cytokine and chemokine release patterns and recruitment of inflammatory cells. Recent data also indicates that proinflammatory cytokine levels are elevated in pregnancy, which might be pivotal in the pathogenesis and the severity of intestinal and extraintestinal symptoms. We present and discuss a diagnostic algorithm and an overall therapeutic rationale for Sweet's syndrome. Copyright Georg Thieme Verlag KG Stuttgart. New York.

Internal movement of estuarine digenetic trematodes through their intermediate snail host Cerithidea californica.

PubMed

Oates, Jessica; Fingerut, Jonathan

2011-12-01

The ability of free-swimming larval parasites to control emergence from their hosts can be critical in increasing the chances of successful infection transmission. For a group of estuarine trematodes, emergence of cercariae from their snail hosts is known to match favorable temperature, tidal activity, and light intensity. How the larvae time this behavior is not well understood, but the pathway that the larvae take through their host may play a role. Through video and histological analysis, we were able to identify the snail's anus as the emergence point and the peri-intestinal sinus dorsal to the intestines as the route by which they reach that point. By moving through this open sinus, the larvae have an energetically efficient pathway to reach their emergence point while minimizing damage to the host. Most importantly, it allows control over emergence to be maintained by the parasite, not the host, thus increasing the chances of the larva successfully reaching its intended destination.

Celiac Disease: Role of the Epithelial Barrier.

PubMed

Schumann, Michael; Siegmund, Britta; Schulzke, Jörg D; Fromm, Michael

2017-03-01

In celiac disease (CD) a T-cell-mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed.

Effect of relative volume on radio transmitter expulsion in subadult common carp

USGS Publications Warehouse

Penne, C.R.; Ahrens, N.L.; Summerfelt, R.C.; Pierce, C.L.

2007-01-01

Expulsion of surgically implanted radio transmitters is a problem in some fish telemetry studies. We conducted a 109-d experiment to test the hypothesis that variation in relative volume of transmitters surgically implanted in subadult common carp Cyprinus carpio would affect transmitter expulsion. We also necropsied fish at the end of the experiment to evaluate histological evidence for the mechanism of expulsion. Survival rate was high during our experiment; all control fish and 88% of the fish subjected to the implantation surgery survived. Expulsion rate was low; of the 23 fish that received transmitters and survived the experiment, only two (9%) expelled the transmitters. One of these expulsions occurred through a rupture of the incision and the other occurred via the intestine. Retained transmitters were all encapsulated by tissue, and most exhibited multiple adhesions to the intestine, gonads, and body wall. Adhesions were more numerous in fish that received larger transmitters. ?? Copyright by the American Fisheries Society 2007.

Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

PubMed

Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

2015-01-01

Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora.

PubMed

Adachi, Soichiro; Hoshi, Namiko; Inoue, Jun; Yasutomi, Eiichiro; Otsuka, Takafumi; Dhakhwa, Ramesh; Wang, Zi; Koo, Yuna; Takamatsu, Toshihiro; Matsumura, Yuriko; Yamairi, Haruka; Watanabe, Daisuke; Ooi, Makoto; Tanahashi, Toshihito; Nishiumi, Shin; Yoshida, Masaru; Azuma, Takeshi

2017-01-01

Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions). © 2017 S. Karger AG, Basel.

Gastric intestinal metaplasia is associated with gastric dysplasia but is inversely correlated with esophageal dysplasia

PubMed Central

Gomez, Justin M; Patrie, James T; Bleibel, Wissam; Frye, Jeanetta W; Sauer, Bryan G; Shami, Vanessa M; Stelow, Edward B; Moskaluk, Christopher A; Wang, Andrew Y

2017-01-01

AIM To determine which clinical factors might be associated with gastric intestinal metaplasia (IM) in a North American population. METHODS Pathology and endoscopy databases at an academic medical center were reviewed to identify patients with and without gastric IM on biopsies for a retrospective cohort study. Patient demographics, insurance status, and other clinical factors were reviewed. RESULTS Four hundred and sixty-eight patients with gastric IM (mean age: 61.0 years ± 14.4 years, 55.5% female) and 171 without gastric IM (mean age: 48.8 years ± 20.8 years, 55.0% female) were compared. The endoscopic appearance of atrophic gastritis correlated with finding gastric IM on histopathology (OR = 2.05, P = 0.051). Gastric IM was associated with histologic findings of chronic gastritis (OR = 2.56, P < 0.001), gastric ulcer (OR = 6.97, P = 0.015), gastric dysplasia (OR = 6.11, P = 0.038), and gastric cancer (OR = 6.53, P = 0.027). Histologic findings of Barrett’s esophagus (OR = 0.28, P = 0.003) and esophageal dysplasia (OR = 0.11, P = 0.014) were inversely associated with gastric IM. Tobacco use (OR = 1.73, P = 0.005) was associated with gastric IM. CONCLUSION Patients who smoke or have the endoscopic finding of atrophic gastritis are more likely to have gastric IM and should have screening gastric biopsies during esophagogastroduodenoscopy (EGD). Patients with gastric IM are at increased risk for having gastric dysplasia and cancer, and surveillance EGD with gastric biopsies in these patients might be reasonable. PMID:28250898

Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

PubMed

Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

2013-08-01

Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p < 0.05). Histological parameters, such as crypt depth and villus height, were also significantly decreased by doxorubicin. TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice

PubMed Central

Wisniewski, Paul J.; Noji, Michael; McGuinness, Lora R.; Lightfoot, Stanley A.

2016-01-01

Background The gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet. Methods Thirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons. Results Lean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp. Conclusion These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host. PMID:26954359

Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction.

PubMed

Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu

2014-01-01

Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non-Barrett's adenocarcinoma with gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including Barrett's esophagus-related, positive gastritis-related, and Barrett's esophagus and gastritis-unrelated adenocarcinoma of the esophagogastric junction.

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

PubMed Central

Mazzucchelli, L.; Hauser, C.; Zgraggen, K.; Wagner, H.; Hess, M.; Laissue, J. A.; Mueller, C.

1994-01-01

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178948

Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.

PubMed

Karadag, Ahmet; Ozdemir, Ramazan; Kurt, Ahmet; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Taslidere, Elif; Karaman, Abdurrahman

2015-07-01

In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively). Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

PubMed

Hokari, Ryota; Kitagawa, Noritake; Watanabe, Chikako; Komoto, Shunsuke; Kurihara, Chie; Okada, Yoshikiyo; Kawaguchi, Atsushi; Nagao, Shigeaki; Hibi, Toshifumi; Miura, Soichiro

2008-07-01

Vascular endothelial growth factor receptor 3 (VEGFR3) and LYVE-1 are specifically expressed in the endothelium of the lymphatic systems. VEGF-C, D, FOXC2, Prox 1, and SOX18 are known to play central roles in lymphatic development. We investigated the expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa of idiopathic intestinal lymphangiectasia. Biopsy samples were obtained from duodenal biopsies in patients with intestinal lymphangiectasia complicated with protein-losing from white spot lesions in which lymphangiectasia was histologically confirmed. Immunohistochemical analysis for VEGFR3 and LYVE-1 was performed. mRNA expression of VEGF-C, VEGF-D, VEGFR3, and transcription factors was determined by the quantitative reverse transcription-polymerase chain reaction method. In the control mucosa, VEGFR3 was weakly expressed on the central lymphatic vessels in the lamina propria and LYVE-1 was expressed mainly on the lymphatic vessels in the submucosa. In intestinal lymphangiectasia, VEGFR3 and LYVE-1 expression levels were increased on the mucosal surface corresponding to widely dilated lymphatic vessels, while they were decreased in the deeper mucosa. mRNA expression study showed a significant increase in the expression level of VEGFR3 in lymphangiectasia, but the expression of VEGF-C and -D mRNA was significantly suppressed compared with that in controls despite the presence of lymphangiectasia. The mRNA expression levels of FOXC2 and SOX18 were also decreased, whereas Prox 1 was not altered. There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.

Adaptations to the air breathing in the posterior intestine of the catfish (Corydoras aeneus, Callichthyidae). A histological and ultrastructural study.

PubMed

Podkowa, Dagmara; Goniakowska-Witalińska, Lucyna

2002-01-01

A light and transmission electron microscopic study of the intestine of catfish C. aeneus shows that the anterior part of the intestine is a site of digestion and absorption and its structure is typical of that of other teleostean fishes. However, in this species the thin-walled posterior intestine is adapted to air breathing. In this region mucosa is smooth and lined with respiratory epithelium with capillary network. Several types of cells are observed in the epithelium: flattened respiratory epithelial cells with short microvili, goblet cells, scarce epithelial cells with numerous longer microvilli, and two types of endocrine cells (EC). The solitary brush cells with several long and thick microvilli described here are the first observation of such cells in the gastrointestinal tract of fishes. Bodies of respiratory epithelial cells lie between capillaries. Their cytoplasm, apart from typical organelles contains dense and lamellar bodies, which are a site of accumulation of surfactant. In regions where capillaries are covered by thin cytoplasmic sheets of respiratory epithelial cells, a thin (0.24-3.00 microm) air-blood barrier is formed, thus enabling gas exchange. Epithelial cells with longer microvilli do not participate in the formation of the air-blood barrier and are probably responsible for absorbtion. EC of the closed type are dispersed within the epithelium. Their cytoplasm contains characteristic round or oval dense core vesicles 69 to 230 nm in diameter. The role of EC and brush cells in the regulation of processes related to absorbtion, and to respiration, is disscused.

Labrasol® and Salts of Medium-Chain Fatty Acids Can Be Combined in Low Concentrations to Increase the Permeability of a Macromolecule Marker Across Isolated Rat Intestinal Mucosae.

PubMed

Heade, Joanne; Maher, Sam; Bleiel, Sinead B; Brayden, David J

2018-06-01

In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol ® ) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C 10 ), sodium undecylenate (C 11:1 ), or sodium laurate (C 12 ) combined with Labrasol ® increased the apparent permeability coefficient (P app ) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol ® alone. For example, combination of C 11:1 (0.5 mg/mL) with Labrasol ® (1 mg/mL) increased the P app of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol ® increased the P app of FD4 to values greater than those seen for MCFAs or Labrasol ® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Alteration of intestinal barrier function during activity-based anorexia in mice.

PubMed

Jésus, Pierre; Ouelaa, Wassila; François, Marie; Riachy, Lina; Guérin, Charlène; Aziz, Moutaz; Do Rego, Jean-Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Coëffier, Moïse

2014-12-01

Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa. Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA. On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p < 0.001) and weight loss was more pronounced in ABA and PF compared to LFA mice (23.6 ± 1.6% and 24.7 ± 0.7% vs. 16.5 ± 1.2%; p < 0.05). Colonic histology showed decreased thickness of the muscularis layer in ABA compared to LFA mice (p < 0.05). Colonic permeability was increased in both ABA and PF compared to LFA mice (p < 0.05) but jejunal paracellular permeability was not affected. Expression of claudin-1 in the colon was lower in the ABA than the LFA group (p < 0.05), whereas occludin expression remained unaffected. Increased colonic permeability and histological alterations found in ABA mice suggest that intestinal barrier dysfunction may also occur in anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Autoimmune gastritis: Pathologist's viewpoint.

PubMed

Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

2015-11-14

Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

Autoimmune gastritis: Pathologist’s viewpoint

PubMed Central

Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

2015-01-01

Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling. PMID:26576102

Barrett’s Esophagus: Frequency and Prediction of Dysplasia and Cancer

PubMed Central

Falk, Gary W.

2015-01-01

The incidence of esophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett’s esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma, but the overwhelming majority of patients with Barrett’s esophagus will never develop esophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett’s esophagus patients at increased risk for progression to high-grade dysplasia and esophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as esophagitis and the 12 to 6 o’clock hemisphere of the esophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett’s esophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include aging, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. PMID:25743461

Barrett's oesophagus: frequency and prediction of dysplasia and cancer.

PubMed

Falk, Gary W

2015-02-01

The incidence of oesophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett's oesophagus is a clearly recognized risk factor for the development of oesophageal adenocarcinoma, but the overwhelming majority of patients with Barrett's oesophagus will never develop oesophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett's oesophagus patients at increased risk for progression to high-grade dysplasia and oesophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as oesophagitis and the 12 to 6 o'clock hemisphere of the oesophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett's oesophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include ageing, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

Incidence and survival of sinonasal adenocarcinoma by site and histologic subtype.

PubMed

Kılıç, Suat; Samarrai, Ruwaa; Kılıç, Sarah S; Mikhael, Mina; Baredes, Soly; Eloy, Jean Anderson

2018-04-01

To determine the incidence and survival of sinonasal adenocarcinoma (SNAC) by subsite and histologic subtype. Retrospective database review. Using the SEER database, we performed a retrospective analysis, identified cases of SNAC diagnosed between 1973 and 2013 and analyzed demographic, histopathology, clinicopathology, and determinants of disease specific survival (DSS). A total of 746 patients with SNAC were identified. Median age at diagnosis was 64 years. Overall incidence was 0.44 per million, and was higher among blacks (O.R.:1.10-2.07:1) and males (O.R.:1.38-2.06:1). Nasal cavity (41.5%) was the most common site, followed by maxillary (26.5%), and ethmoid (17.4%) sinuses. Intestinal-type adenocarcinoma was less likely than Adenocarcinoma not otherwise specified (ANOS) to be found in the maxillary sinus (8.8% vs. 30.6%, p < .05). Surgery alone (48.56%) was the most common treatment modality, followed by surgery and radiotherapy (RT) (32.5%), and RT alone (11.6%). DSS at 5, 10, and 20 years were 63.8%, 57.6%, and 47.0%, respectively. DSS was higher for nasal cavity SNAC, lower grade, lower stage, and those receiving surgery only. SNAC is more common among men and blacks. Incidence has not changed significantly in the past 40 years. Survival varies with grade, stage, histology, subsite, and treatment.

Characterization of the contents and histology of the gastrointestinal tracts of White Sturgeon (Acipenser transmontanus) captured from Upper Lake Roosevelt, Washington, October 2008

USGS Publications Warehouse

Parsley, Michael J.; van der Leeuw, Bjorn K.; Elliott, Diane G.

2010-01-01

The gastrointestinal tracts of 37 juvenile white sturgeon (Acipenser transmontanus) captured from the upper part of Lake Roosevelt during October 2008, were examined to identify prey taxa and to determine if the fish were consuming smelter slag along with other sediments. Histological examination of the gastrointestinal tract tissues and comparison with similar tissues from hatchery-reared fish also was performed. The contents of the gastro-intestinal tracts (guts) indicated that white sturgeon were actively foraging on various benthic invertebrates and the diet was quite diverse, with more than 50 percent of the fish feeding on five or more different taxa. Slag was present in 76 percent of the guts examined. Although not all guts contained slag particles, larger fish tended to have greater amounts of slag in their guts. Histology of the gut tissues showed the presence of a chronic inflammatory response, and the severity of the response had a significant positive correlation (P = 0.01) with fish length and weight suggesting that the inflammation represented a response to long-term exposure to one or more stressors. However, additional work is needed to determine if the physical or chemical properties of slag contributed to this response.

Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

PubMed Central

Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

2016-01-01

This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. PMID:27058552

First survey of Cryptosporidium, Giardia and Enterocytozoon in diarrhoeic children from Wuhan, China.

PubMed

Wang, Tao; Fan, Yingying; Koehler, Anson V; Ma, Guangxu; Li, Tao; Hu, Min; Gasser, Robin B

2017-07-01

Intestinal protozoan pathogens cause significant diarrhoeal diseases in children. However, to date, there has been limited genetic study of the intestinal pathogens Cryptosporidium, Giardia and Enterocytozoon in humans in China, with the exception of research in a small number of cities/provinces. In the present study, PCR-based tools were used to detect and characterise these protistan parasites from 500 children with a history of diarrhoea in Wuhan and environs, Hubei province, China. Genomic DNAs from faecal samples were screened for the particular protists by PCR utilising regions in the small subunit (SSU) of the nuclear ribosomal RNA, the 60kDa glycoprotein (gp60), the internal transcribed spacer of nuclear ribosomal DNA (ITS) and/or the triose phosphate isomerase (tpi) genes as markers. Cryptosporidium meleagridis subtype IIIb (10/500, 2.0%), Giardia duodenalis assemblage A (7/500, 1.4%) and Enterocytozoon bieneusi genotype D (1/500, 0.2%) were identified in small percentages of the 500 samples. No significant gender- or age-associated differences in the prevalence of Cryptosporidium and Giardia infections were found. Future studies might focus on the occurrence of these protists in children as well as animals, with an emphasis on Cryptosporidium meleagridis in pets and agriculturally important birds, in different parts of Hubei province. Copyright © 2017 Elsevier B.V. All rights reserved.

Immune Organs and Haemopoietic System Under Modelling of the Mission Factors

NASA Astrophysics Data System (ADS)

Sapin, M. R.; Grigoriev, A. I.; Erofeeva, L. M.; Grigorenko, D. E.; Fedorenko, B. S.

1997-07-01

Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model are given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.

Laboratory Maintenance of Helicobacter Species

PubMed Central

Blanchard, Thomas G.; Nedrud, John G.

2012-01-01

Helicobacter species are Gram-negative bacteria that colonize the gastric or intestinal mucosa of many mammalian and avian hosts and induce histologic inflammation. The association of H. pylori with gastritis, peptic ulcer disease, and gastric cancers makes it a significant human pathogen. Animal models for these diseases are being used to explore the pathogenesis of H. pylori infection and in vaccine development (UNIT 8B.1). Both bacterial and host factors contribute to Helicobacter pathogenesis, and therefore the microbiology is very important. This unit describes how to culture the most commonly used gastric Helicobacter species, H. pylori, H. mustelae, and H. felis. PMID:18770594

Histological development of the digestive system of the Amazonian pimelodid catfish Pseudoplatystoma punctifer.

PubMed

Gisbert, E; Moreira, C; Castro-Ruiz, D; Oztürk, S; Fernández, C; Gilles, S; Nuñez, J; Duponchelle, F; Tello, S; Renno, J F; García-Dávila, C; Darias, M J

2014-11-01

The organogenesis of the digestive system was described in the Amazonian pimelodid catfish species Pseudoplatystoma punctifer from hatching (3.5 mm total length, TL) to 41 days post-fertilization (dpf) (58.1 mm TL) reared at 28°C. Newly hatched larvae showed a simple digestive tract, which appeared as a straight undifferentiated and unfolded tube lined by a single layer of columnar epithelial cells (future enterocytes). During the endogenous feeding period, comprised between 20 and 96 h post-fertilization (3.5 to 6.1 mm TL), the larval digestive system experienced a fast transformation with the almost complete development and differentiation of most of digestive organs (buccopahrynx, oesophagus, intestine, liver and exocrine pancreas). Yolk reserves were not completely depleted at the onset of exogenous feeding (4 dpf, 6.1 mm TL), and a period of mixed nutrition was observed up to 6 to 7 dpf (6.8 to 7.3 mm TL) when yolk was definitively exhausted. The stomach was the organ that latest achieved its complete differentiation, characterized by the development of abundant gastric glands in the fundic stomach between 10 and 15 dpf (10.9 to 15.8 mm TL) and the formation of the pyloric sphincter at the junction of the pyloric stomach and the anterior intestine at 15 dpf (15.8 mm TL). The above-mentioned morphological and histological features observed suggested the achievement of a digestive system characteristic of P. punctifer juveniles and adults. The ontogeny of the digestive system in P. punctifer followed the same general pattern as in most Siluriform species so far, although some species-specific differences in the timing of differentiation of several digestive structures were noted, which might be related to different reproductive guilds, egg and larval size or even different larval rearing practices. According to present findings on the histological development of the digestive system in P. punctifer, some recommendations regarding the rearing practices of this species are also provided in order to improve the actual larval rearing techniques of this fast-growing Neotropical catfish species.

Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

PubMed Central

Tian, Xiao-Feng; Yao, Ji-Hong; Li, Ying-Hua; Zhang, Xue-Song; Feng, Bing-An; Yang, Chun-Ming; Zheng, Shu-Sen

2006-01-01

AIM: To investigate the role of nuclear factor kappa B (NF-κB) in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R), and its effect on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. METHODS: Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate (PDTC) treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery (SMA) occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid (BALF) protein were assayed. Serum IL-6, lung malondialdehyde (MDA) and myeloperoxidase (MPO) as well as the expression level of NF-κB and ICAM-1 were measured. RESULTS: Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group (P = 0.001). Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly (P < 0.05) when compared to I/R group. CONCLUSION: The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB. PMID:16489637

Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1.

PubMed

Mah, Amanda T; Van Landeghem, Laurianne; Gavin, Hannah E; Magness, Scott T; Lund, P Kay

2014-09-01

Nutrient intake regulates intestinal epithelial mass and crypt proliferation. Recent findings in model organisms and rodents indicate nutrient restriction impacts intestinal stem cells (ISC). Little is known about the impact of diet-induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9-EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP mice were fed a high-fat diet for 20 weeks to induce DIO and compared with littermates fed low-fat rodent chow. Histology, fluorescence activated cell sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus morphometry, numbers, and proliferation of different Sox9-EGFP cell populations and gene expression. An in vitro culture assay directly assessed functional capacity of isolated ISC. DIO mice exhibited significant increases in body weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density but decreased intestinal length and decreased numbers of Paneth and goblet cells. In vivo, DIO resulted in a selective expansion of Sox9-EGFP(Low) ISC and percentage of ISC in S-phase. ISC expansion significantly correlated with plasma insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in standard 3D Matrigel culture compared to controls, indicating impaired ISC function. This decreased enteroid formation in isolated ISC from DIO mice was rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces specific increases in ISC and ISC hyperproliferation in vivo. However, isolated ISC from DIO mice have impaired intrinsic survival and growth in vitro that can be rescued by exogenous insulin or IGF1.

The pathogenesis of single experimental infections with Strongylus vulgaris in foals.

PubMed

Duncan, J L; Pirie, H M

1975-01-01

The clinical signs, pathology and clinical pathology associated with single experimental infections of Strongylus vulgaris in worm-free pony foals are described. The major clinical signs which became apparent in the infected foals during the first three weeks were pyrexia, anorexia, dullness and abdominal pain. Within the first two weeks of infection lesions were confined to the intestine and terminal branches of the intestinal arteries and consisted of mucosal, submucosal and serosal haemorrhage together with arteritis of submucosal and serosal arteries and also a marked inflammatory reaction. The main lesion seen three weeks after infection was gross thrombosis of the anterior mesenteric artery or one of its major branches. On section these affected arteries showed marked intimal thickening with infiltration of plasma cells, lymphocytes, macrophages and neutrophils. Between one and four months after infection the gross lesions were predominantly in the arteries and consisted of fibrous thickening of the arterial wall and thrombosis associated with the presence of developing fourth stage larvae. Four months after infection the arterial lesions were still prominent and microscopically there was fibrosis of the wall of the affected artery with wide-spread disruption of the intima. In the adventitia organised thrombi were apparent in the vasa vasorum and resulted in the obliteration of their lumina. The typical lesion associated with the return of fifth stage larvae to the intestine was nodule formation in close proximity to thrombosed terminal intestinal arteries and sections of parasites were seen in the intestinal wall surrounded by neutrophils and necrotic debris. By nine months after infection the arterial lesion had healed, but histologically there was fibrosis of the intima and macrophages containing haemosiderin were seen in the arterial wall. The most significant haematological findings during the experimental period were a marked polymorphonuclear leucocytosis and an increase in the number of circulating eosinophils in the infected animals. Also marked was an increase in the serum globulin levels of the infected foals.

Modulation of Intestinal Inflammation by Yeasts and Cell Wall Extracts: Strain Dependence and Unexpected Anti-Inflammatory Role of Glucan Fractions

PubMed Central

Jawhara, Samir; Habib, Khalid; Maggiotto, François; Pignede, Georges; Vandekerckove, Pascal; Maes, Emmanuel; Dubuquoy, Laurent; Fontaine, Thierry; Guerardel, Yann; Poulain, Daniel

2012-01-01

Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS) for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4), as well as mannoprotein (MP) and β-glucan crude fractions prepared from Sc2 and highly purified β-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNFα and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas β-glucan fraction was protective against both. Surprisingly, purified β-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that β-glucan fractions or pure β-glucans from C. albicans displayed the most potent anti-inflammatory effect in the DSS model. PMID:22848391

Protein source and nutrient density in the diets of male broilers from 8 to 21 d of age: Effects on small intestine morphology.

PubMed

Wang, X; Peebles, E D; Morgan, T W; Harkess, R L; Zhai, W

2015-01-01

In a companion study, high amino acid (AA) or apparent metabolizable energy (AME) densities in the diets of broilers from 8 to 21 d of age were found to improve feed conversion. A total of 1,120 male Ross×Ross 708 chicks were randomly allocated to 80 pens (8 treatments, 10 replications per treatment, 14 chicks per pen). A 2×2×2 factorial arrangement of treatments was used to investigate the interaction among the protein source (high distillers dried grains with solubles diet [hDDGS] or high meat and bone meal diet [hMBM]), AA density (moderate or high), and AME density (2,998 or 3,100 kcal/kg) of diets on small intestine morphology. Duodenum, jejunum, and ileum samples from 2 chicks per pen were collected and measured individually at 21 d. Jejunum sections were processed for histological analysis. Chicks fed hDDGS diets exhibited longer small intestines than did chicks fed hMBM diets. Particularly, when chicks were fed high AA density diets, jejuna were longer in groups fed hDDGS diets than groups fed hMBM diets. Dietary treatments did not affect jejunum villus height, width, area, crypt depth, villus to crypt ratio, goblet cell size, or cell density. In birds fed diets containing a moderate AA and a high AME density, jejunum muscle layers of chicks fed hDDGS diets were thicker than those fed hMBM diets. Chicks exhibited a lower feed conversion ratio (FCR) and a higher BW gain when their crypts were shorter. In conclusion, an hDDGS diet may facilitate small intestine longitudinal growth in broilers, which may subsequently improve dietary nutrient absorption. In addition, broiler chicks with shallow intestinal crypts exhibited better growth performance. © 2014 Poultry Science Association Inc.

Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice.

PubMed

Yu, Yi; Feng, Xiaoyan; Vieten, Gertrud; Dippel, Stephanie; Imvised, Tawan; Gueler, Faikah; Ure, Benno M; Kuebler, Jochen F; Klemann, Christian

2017-01-01

Ischemia-reperfusion injury (IRI) is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αβ T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αβ T cells play in IRI to the gut. Adult wild-type (WT) and αβ T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI. Intestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αβ T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αβ T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable. An increasing body of evidence demonstrates that αβ T cells play a key role in IRI. In the gut, however, αβ T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αβ T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis.

PubMed

Matsumoto, Kotaro; Ichimura, Mayuko; Tsuneyama, Koichi; Moritoki, Yuki; Tsunashima, Hiromichi; Omagari, Katsuhisa; Hara, Masumi; Yasuda, Ichiro; Miyakawa, Hiroshi; Kikuchi, Kentaro

2017-01-01

Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet. Fecal bacteria, short-chain fatty acids, and immunoglobulin A (IgA) levels were investigated. Histological and immunohistochemical examinations were performed using mice livers for CD14 and Toll-like receptor-4 (TLR4) expression and intestinal tissue samples for IgA and zonula occludens-1 expression in epithelial tight junctions. The methionine-choline-deficient mice administered 5% fructo-oligosaccharides maintained a normal gastrointestinal microbiome, whereas methionine-choline-deficient mice without prebiotic supplementation displayed increases in Clostridium cluster XI and subcluster XIVa populations and a reduction in Lactobacillales spp. counts. Methionine-choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine-choline-deficient mice that were not administered this prebiotic. This study illustrated that in the methionine-choline-deficient mouse model, dietary fructo-oligosaccharides can restore normal gastrointestinal microflora and normal intestinal epithelial barrier function, and decrease steatohepatitis. The findings support the role of prebiotics, such as fructo-oligosaccharides, in maintaining a normal gastrointestinal microbiome; they also support the need for further studies on preventing or treating nonalcoholic steatohepatitis using dietary fructo-oligosaccharides.

Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice.

PubMed

Li, Nan; Ma, Liya; Liu, Xueyan; Shaw, Lynn; Li Calzi, Sergio; Grant, Maria B; Neu, Josef

2012-04-01

Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model. Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P7-P12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P12-P17). Mouse pups received Arg-Gln (5g·kg·day) or DHA (5g·kg·day) or vehicle orally started on P12 through P17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated. Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (P<0.05). Arg-Gln dipeptide and DHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (P<0.05). Supplementation of Arg-Gln or DHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (P<0.05). Supplementation with either Arg-Gln or DHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism

PubMed Central

Korecka, Agata; Dona, Anthony; Lahiri, Shawon; Tett, Adrian James; Al-Asmakh, Maha; Braniste, Viorica; D’Arienzo, Rossana; Abbaspour, Afrouz; Reichardt, Nicole; Fujii-Kuriyama, Yoshiaki; Rafter, Joseph; Narbad, Arjan; Holmes, Elaine; Nicholson, Jeremy; Arulampalam, Velmurugesan; Pettersson, Sven

2016-01-01

The ligand-induced transcription factor, aryl hydrocarbon receptor (AhR) is known for its capacity to tune adaptive immunity and xenobiotic metabolism—biological properties subject to regulation by the indigenous microbiome. The objective of this study was to probe the postulated microbiome-AhR crosstalk and whether such an axis could influence metabolic homeostasis of the host. Utilising a systems-biology approach combining in-depth 1H-NMR-based metabonomics (plasma, liver and skeletal muscle) with microbiome profiling (small intestine, colon and faeces) of AhR knockout (AhR−/−) and wild-type (AhR+/+) mice, we assessed AhR function in host metabolism. Microbiome metabolites such as short-chain fatty acids were found to regulate AhR and its target genes in liver and intestine. The AhR signalling pathway, in turn, was able to influence microbiome composition in the small intestine as evident from microbiota profiling of the AhR+/+ and AhR−/− mice fed with diet enriched with a specific AhR ligand or diet depleted of any known AhR ligands. The AhR−/− mice also displayed increased levels of corticosterol and alanine in serum. In addition, activation of gluconeogenic genes in the AhR−/− mice was indicative of on-going metabolic stress. Reduced levels of ketone bodies and reduced expression of genes involved in fatty acid metabolism in the liver further underscored this observation. Interestingly, exposing AhR−/− mice to a high-fat diet showed resilience to glucose intolerance. Our data suggest the existence of a bidirectional AhR-microbiome axis, which influences host metabolic pathways. PMID:28721249

Celiac disease and intestinal metaplasia of the esophagus (Barrett's esophagus).

PubMed

Maieron, Roberto; Elli, Luca; Marino, Marco; Floriani, Irene; Minerva, Francesco; Avellini, Claudio; Falconieri, Giovanni; Pizzolitto, Stefano; Zilli, Maurizio

2005-01-01

Previous studies on celiac patients demonstrated that exposure to gliadin alters the motility of the upper gastrointestinal tract, leading to increased acid reflux. No literature is available regarding the possible presence of specialized intestinal metaplasia of the esophagus as a consequence of chronic reflux in adult celiac patients. Our purpose was to evaluate endoscopically and histologically the esophagi of a group of untreated celiac patients. We studied 60 celiac patients, 13 men and 47 women (mean age, 40 +/- 14 [SD] years; range, 18-80 years), at their first endoscopy (following a normal diet). The distal esophagus was evaluated and multiple biopsies were taken. Hematoxylin-eosin and alcian blue stainings were performed. A group of nonceliac, age- and sex-matched patients was used as a control. We found intestinal metaplasia in the distal esophagus of 16 of 60 (26.6%) celiacs (mean age, 45 +/- 13 years; range, 27-75 years), in comparison with a control-group prevalence of 10.9% (OR, 3.9; 95% CI, 1.4-11.2%). Among the celiac group with metaplasia, only one patient had reflux-like symptoms. None had esophagitis. In conclusion, we observed an increased prevalence of esophageal metaplasia in patients with celiac disease. This finding could be the result of motor abnormalities leading to chronic acid reflux, combined with a mucosa which is sensitive to gliadin.

Alleviation of 5-fluorouracil-induced intestinal mucositis in rats by vitamin E via targeting oxidative stress and inflammatory markers.

PubMed

Al-Asmari, Abdulrahman Khazim; Khan, Abdul Quaiyoom; Al-Asmari, Sarah A; Al-Rawi, Abdulqadir; Al-Omani, Saud

2016-12-01

BackgroundIntestinal mucositis is a major concern related with cancer therapy. It is well established that overproduction of reactive oxygen species and inflammatory mediators plays vital role in the pathogenesis of mucositis. The aim of the study was to investigate the modulatory effect of vitamin E (vit. E) on 5-fluorouracil (5-FU)-induced intestinal mucositis by targeting oxidative stress and inflammatory markers in rats. MethodsRats were randomly divided into four groups of six animals each. All four-group animals received normal standard diet and water throughout the experimental period which last up to 10 days. Rats were gavaged with vit. E (300 mg/kg b. wt.) daily for 10 days (day 1-10) and were given intraperitoneal injection of 5-FU (150 mg/kg b. wt.) or saline (control) on day 8 to induce mucositis. Results We found that vit. E supplementation ameliorated 5-FU-induced lipid peroxidation, myeloperoxidase activity, activation of nuclear factor κB, expression of cyclooxygenase-2, inducible nitric oxide synthase and mucin depletion. Vit. E administration also attenuated 5-FU-induced histological anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. ConclusionsFindings of the study suggest that vit. E inhibits 5-FU-induced mucositis via modulation of oxidative stress, activation of redox sensitive transcription factor and its downstream targets.

Evaluation of Small Intestine Grafts Decellularization Methods for Corneal Tissue Engineering

PubMed Central

Oliveira, Ana Celeste; Garzón, Ingrid; Ionescu, Ana Maria; Carriel, Victor; Cardona, Juan de la Cruz; González-Andrades, Miguel; Pérez, María del Mar; Alaminos, Miguel; Campos, Antonio

2013-01-01

Advances in the development of cornea substitutes by tissue engineering techniques have focused on the use of decellularized tissue scaffolds. In this work, we evaluated different chemical and physical decellularization methods on small intestine tissues to determine the most appropriate decellularization protocols for corneal applications. Our results revealed that the most efficient decellularization agents were the SDS and triton X-100 detergents, which were able to efficiently remove most cell nuclei and residual DNA. Histological and histochemical analyses revealed that collagen fibers were preserved upon decellularization with triton X-100, NaCl and sonication, whereas reticular fibers were properly preserved by decellularization with UV exposure. Extracellular matrix glycoproteins were preserved after decellularization with SDS, triton X-100 and sonication, whereas proteoglycans were not affected by any of the decellularization protocols. Tissue transparency was significantly higher than control non-decellularized tissues for all protocols, although the best light transmittance results were found in tissues decellularized with SDS and triton X-100. In conclusion, our results suggest that decellularized intestinal grafts could be used as biological scaffolds for cornea tissue engineering. Decellularization with triton X-100 was able to efficiently remove all cells from the tissues while preserving tissue structure and most fibrillar and non-fibrillar extracellular matrix components, suggesting that this specific decellularization agent could be safely used for efficient decellularization of SI tissues for cornea TE applications. PMID:23799114

Raccoons (Procyon lotor) as Sentinels of Trace Element Contamination and Physiological Effects of Exposure to Coal Fly Ash

DOE PAGES

Hernandez, Felipe; Oldenkamp, Ricki E.; Webster, Sarah; ...

2016-12-08

Anthropogenic pollutants disrupt global biodiversity, and terrestrial sentinels of pollution can provide a warning system for ecosystem-wide contamination. This study sought to assess whether raccoons (Procyon lotor) are sentinels of local exposure to trace element contaminants at a coal fly ash site and whether exposure resulted in health impairment or changes in the intestinal helminth communities. We compared trace element accumulation and the impact on health responses and intestinal helminth communities of raccoons inhabiting contaminated and reference sites of the U.S. Department of Energy’s Savannah River Site (South Carolina, USA). Data on morphometry, hematology, histopathology, helminth community and abundance, andmore » liver trace element burdens were collected from 15 raccoons captured adjacent to a coal fly ash basin and 11 raccoons from a comparable uncontaminated site nearby. Of eight trace elements analyzed, Cu, As, Se, and Pb were elevated in raccoons from the contaminated site. Raccoons from the contaminated site harbored higher helminth abundance than animals from the reference site and that abundance was positively associated with increased Cu concentrations. While we found changes in hematology associated with increased Se exposure, we did not find physiological or histological changes associated with higher levels of contaminants. Our results suggest that raccoons and their intestinal helminths act as sentinels of trace elements in the environment associated with coal fly ash contamination.« less

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

PubMed Central

Liu, Yuan; Wang, Xin-Yue; Yang, Xue; Jing, Shan; Zhu, Li; Gao, Si-Hua

2013-01-01

Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC) rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A) in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage. PMID:23606829

Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation.

PubMed

Sun, Y-Q; Xu, L-P; Han, T-T; Zhang, X-H; Wang, Y; Han, W; Wang, F-R; Wang, J-Z; Chen, H; Chen, Y-H; Yan, C-H; Chen, Y; Liu, K-Y; Huang, X-J

2015-10-01

Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Impaired Intestinal Mucosal Barrier upon Ischemia-Reperfusion: “Patching Holes in the Shield with a Simple Surgical Method”

PubMed Central

Rosero, Olivér; Ónody, Péter; Molnár, Dávid; Lotz, Gábor; Turóczi, Zsolt; Fülöp, András; Garbaisz, Dávid; Harsányi, László; Szijártó, Attila

2014-01-01

Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. Methods. Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. Results. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF-α levels were significantly lower in the PC-group compared to the IR-group. Conclusion. The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response. PMID:24955347

Chronic Exposure to Rifaximin Causes Hepatic Steatosis in Pregnane X Receptor-Humanized Mice

PubMed Central

Gonzalez, Frank, J.

2012-01-01

Rifaximin, a nonsystemic antibiotic that exhibits low gastrointestinal absorption, is a potent agonist of human pregnane X receptor (PXR), which contributes to its therapeutic efficacy in inflammatory bowel disease. To investigate the effects of long-term administration of rifaximin on the liver, PXR-humanized mice were administered rifaximin for 6 months; wild-type and Pxr-null mice were treated in parallel as controls. Histological analysis revealed time-dependent intense hepatocellular fatty degeneration and increased hepatic triglycerides in PXR-humanized mice and not in wild-type and Pxr-null mice. After long-term treatment, PXR target genes were induced in small intestine and liver, with significant up-regulation in the expression of hepatic genes related to triglyceride synthesis and lipid accumulation. However, no significant hepatic accumulation of rifaximin was found, even after 6 months of treatment, in PXR-humanized mice. Genes in the small intestine that are involved in the uptake of fatty acids and triglycerides were induced along with increased triglyceride accumulation in intestinal epithelial cells of PXR-humanized mice; this was not observed in wild-type and Pxr-null mice. These findings suggest that long-term administration of rifaximin could lead to PXR-dependent hepatocellular fatty degeneration as a result of activation of genes involved in lipid uptake, thus indicating a potential adverse effect of rifaximin on liver function after long-term exposure. PMID:22790967

What a practitioner needs to know about celiac disease?

PubMed

Garg, Kapil; Gupta, R K

2015-02-01

Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and is characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes and enteropathy. CD is triggered by wheat gluten and related prolamines in barley and rye. Worldwide, the disease affects approximately 1 % of the general population. Clinical features of CD vary considerably. Intestinal symptoms are more common in young children. In older children extra intestinal manifestations affecting almost all organs are seen. IgA tTG antibody, upper GI endoscopy with histological analysis of multiple biopsies of the duodenum and in selected cases HLA DQ2 and DQ8 positivity and endomysial antibodies (EMA) are needed for diagnosis. Currently, the only treatment for CD is a life-long gluten-free diet (GFD). Strict avoidance of wheat, rye, barley and their derivatives will result in intestinal healing and relief of symptoms for the majority of individuals with CD. The GFD is simple in principle, however, completely eliminating all foods and ingredients containing wheat, rye, barley, and most commercial oats can be very challenging. Newly diagnosed CD children should undergo testing and treatment for micronutrient deficiencies specially iron, folic acid, vitamin D, and vitamin B12. Long-term monitoring and follow up of patients with CD is necessary.

Protective Effects of Vitamin E on Methotrexate-Induced Jejunal Mucosal Damage in Rats.

PubMed

Burcu, Busra; Kanter, Mehmet; Orhon, Zeynep Nur; Yarali, Oguzhan; Karabacak, Rukiye

2016-04-01

To investigate the possible protective effects of Vitamin E (Vit E) on oxidative stress and jejunal damage in the rat intestinal mucosa after methotrexate (MTX)-induced enterotoxicity. Rats were divided into 3 groups: control, MTX, and MTX+ Vit E; each group contained 8 animals. The control group was given physiological serum in addition to sunflower oil for 3 days. The second group was given sunflower oil with intragastric tube daily, followed by MTX injection (20 mg/kg intraperitoneally). To the third group, starting 3 days before injection, Vit E was given dissolved in sunflower oil (600 mg/kg orally) in addition to MTX injection. Four days after MTX injection the anesthetized rats were sacrificed, and the tissue samples obtained from their jejunums were investigated for histological and biochemical analysis. Vit E treatment significantly decreased the elevated tissue malondialdehyde levels and increased the reduced glutathione peroxidase and superoxide dismutase activities in comparison to the MTX-treated group. MTX treatment caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Vit E treatment significantly attenuated the severity of intestinal injury caused by MTX via inhibiting induced nitric oxide synthase levels and NF-κB p65 activation. Because of its reconstructing and antioxidant effects, Vit E pretreatment may have protective effects in the intestinal tissue of MTX-treated rats.

[Expression of neuropeptide Y and long leptin receptor in gastrointestinal tract of giant panda].

PubMed

Luo, Qihui; Tang, Xiuying; Chen, Zhengli; Wang, Kaiyu; Wang, Chengdong; Li, Desheng; Li, Caiwu

2015-08-01

To study the expression and distribution of neuropeptide Y (NPY) and long leptin receptor (OB-Rb) in the gastrointestinal tract of giant panda, samples of three animals were collected from the key laboratory for reproduction and conservation genetics of endangered wildlife of Sichuan province, China conservation and research center for the giant panda. Paraffin sections of giant panda gastrointestinal tissue samples were observed using hematoxylin-eosin staining (HE) and strept actividin-biotin complex immunohistochemical staining (IHC). The results show that the intestinal histology of three pandas was normal and no pathological changes, and there were rich single-cell and multi-cell mucous glands, long intestinal villi and thick muscularis mucosa and muscle layer. Positive cells expressing NPY and OB-Rb were widely detected in the gastrointestinal tract by IHC methods. NPY positive nerve fibers and neuronal cell were widely distributed in submucosal plexus and myenteric plexus, especially in the former. They were arranged beaded or point-like shape. NPY positive cells were observed in the shape of ellipse and polygon and mainly located in the mucous layer and intestinal glands. OB-Rb positive cells were mainly distributed in the mucous layer and the laminae propria, especially the latter. These results confirmed that NPY and OB-Rb are widely distributed in the gut of the giant panda, which provide strong reference for the research between growth and development, digestion and absorption, and immune function.

Turmeric Bioprocessed with Mycelia from the Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Protects Mice Against Salmonellosis.

PubMed

Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

2017-01-01

This study investigated the suppressive mechanisms of an extract from bioprocessed Lentinus edodes mycelial liquid culture supplemented with turmeric (bioprocessed Curcuma longa extract [BPCLE]) against murine salmonellosis. The BPLCE extract from the bioprocessed mycelia of the Salmonella Typhimurium into murine RAW 264.7 macrophage cells, elimination of intracellular bacteria, and elevation of inducible nitric oxide synthase expression. Dietary administration of BPCLE activated leukocytes from the mice infected with Salmonella through the intraperitoneal route. The enzyme-linked immunosorbent assay of the cytokines produced by splenocytes from infected mice showed significant increases in the levels of Th1 cytokines, including interleukin (IL)-1β, IL-2, IL-6, and IL-12. Histology showed that dietary administration of BPCLE protected against necrosis of the liver resulting from a sublethal dose of Salmonella. In addition, the treatment (1) extended the lifespan of lethally infected mice, (2) suppressed the invasion of Salmonella into human Caco-2 colorectal adenocarcinoma cells, (3) increased excretion of the bacterium in the feces, (4) suppressed the translocation of the Salmonella to internal organs, and (5) increased total immunoglobulin A in both serum and intestinal fluids. BPCLE protected the mice against salmonellosis via cooperative effects that include the upregulation of the Th1 immune reaction, prevention of translocation of bacteria across the intestinal epithelial cells, and increased immunoglobulin A production in serum and intestinal fluids.

Raccoons (Procyon lotor) as Sentinels of Trace Element Contamination and Physiological Effects of Exposure to Coal Fly Ash

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez, Felipe; Oldenkamp, Ricki E.; Webster, Sarah

Anthropogenic pollutants disrupt global biodiversity, and terrestrial sentinels of pollution can provide a warning system for ecosystem-wide contamination. This study sought to assess whether raccoons (Procyon lotor) are sentinels of local exposure to trace element contaminants at a coal fly ash site and whether exposure resulted in health impairment or changes in the intestinal helminth communities. We compared trace element accumulation and the impact on health responses and intestinal helminth communities of raccoons inhabiting contaminated and reference sites of the U.S. Department of Energy’s Savannah River Site (South Carolina, USA). Data on morphometry, hematology, histopathology, helminth community and abundance, andmore » liver trace element burdens were collected from 15 raccoons captured adjacent to a coal fly ash basin and 11 raccoons from a comparable uncontaminated site nearby. Of eight trace elements analyzed, Cu, As, Se, and Pb were elevated in raccoons from the contaminated site. Raccoons from the contaminated site harbored higher helminth abundance than animals from the reference site and that abundance was positively associated with increased Cu concentrations. While we found changes in hematology associated with increased Se exposure, we did not find physiological or histological changes associated with higher levels of contaminants. Our results suggest that raccoons and their intestinal helminths act as sentinels of trace elements in the environment associated with coal fly ash contamination.« less

Coeliac disease: review of diagnosis and management.

PubMed

Walker, Marjorie M; Ludvigsson, Jonas F; Sanders, David S

2017-08-21

Coeliac disease is an immune-mediated systemic disease triggered by exposure to gluten, and manifested by small intestinal enteropathy and gastrointestinal and extra-intestinal symptoms. Recent guidelines recommend a concerted use of clear definitions of the disease. In Australia, the most recent estimated prevalence is 1.2% in adult men (1:86) and 1.9% in adult women (1:52). Active case finding is appropriate to diagnose coeliac disease in high risk groups. Diagnosis of coeliac disease is important to prevent nutritional deficiency and long term risk of gastrointestinal malignancy. The diagnosis of coeliac disease depends on clinico-pathological correlation: history, presence of antitransglutaminase antibodies, and characteristic histological features on duodenal biopsy (when the patient is on a gluten-containing diet). Human leucocyte antigen class II haplotypes DQ2 or DQ8 are found in nearly all patients with coeliac disease, but are highly prevalent in the general population at large (56% in Australia) and testing can only exclude coeliac disease for individuals with non-permissive haplotypes. Adhering to a gluten free diet allows duodenal mucosal healing and alleviates symptoms. Patients should be followed up with a yearly review of dietary adherence and a health check. Non-coeliac gluten or wheat protein sensitivity is a syndrome characterised by both gastrointestinal and extra-intestinal symptoms related to the ingestion of gluten and possibly other wheat proteins in people who do not have coeliac disease or wheat allergy recognised by diagnostic tests.

Effects of dietary supplementation of red pepper (Schinus terebinthifolius Raddi) essential oil on performance, small intestinal morphology and microbial counts of weanling pigs.

PubMed

Cairo, Pedro Leon Gomes; Gois, Franz Dias; Sbardella, Maicon; Silveira, Hebert; de Oliveira, Roberto Maciel; Allaman, Ivan Bezerra; Cantarelli, Vinicius Souza; Costa, Leandro Batista

2018-01-01

Many strategies, such as the antibiotic growth promoters, have been developed to improve intestinal health and performance of newly weaned piglets. Natural products such as essential oils have been scientifically recognized as growth enhancer feed additives for weanling pigs, replacing the antibiotics. Therefore, it has been hypothesized that Brazilian red pepper could replace performance-enhancing antibiotics also in weanling pig diets. However, one experiment was conducted to determine the effects of dietary Brazilian red pepper essential oil or antimicrobial growth promoter on intestinal health and growth performance of weanling pigs. No effects of treatments were observed on performance and organ weights (P > 0.05). Overall, both additives [red pepper essential oil (RPEO) or antibiotic (ANT)] increased gut Lactobacillus counts compared to negative control, as well as reduced villi density (P < 0.05). Animals fed diets containing 1.5 g kg -1 RPEO presented the lowest incidence of diarrhea (P < 0.05). Our findings suggested that essential oil from Brazilian red pepper or chlorohydroxyquinoline added in weanling pig diets affect gut microbiota and histology without affecting performance and organ weights. In addition, there was an indication that high doses of essential oil could reduce the incidence of diarrhea. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The novel guanylhydrazone CPSI-2364 ameliorates ischemia reperfusion injury after experimental small bowel transplantation.

PubMed

Websky, Martin von; Fujishiro, Jun; Ohsawa, Ichiro; Praktiknjo, Michael; Wehner, Sven; Abu-Elmagd, Kareem; Kitamura, Koji; Kalff, Joerg C; Schaefer, Nico; Pech, Thomas

2013-06-15

Resident macrophages within the tunica muscularis are known to play a crucial role in initiating severe inflammation in response to ischemia reperfusion injury after intestinal transplantation contributing to graft dysmotility, bacterial translocation, and possibly, acute rejection. The p38 mitogen-activated protein kinase is a key player in the signaling of proinflammatory cytokine synthesis in macrophages. Therefore, we investigated the effects of CPSI-2364, an apparent macrophage-specific inhibitor of the p38 mitogen-activated protein kinase pathway in an isogenic intestinal rat transplantation model. Recipient and donor animals were treated perioperatively with CPSI-2364 (1 mg/kg, intravenously) or vehicle solution. Nontransplanted animals served as control. Animals were killed 30 min, 3 hr, and 18 hr after reperfusion. CPSI-2364 treatment resulted in significantly less leukocyte infiltration and significantly improved graft motor function (18 hr). Messenger RNA expression of proinflammatory cytokines (interleukin 6) and kinetic active mediators (NO) was reduced by CPSI-2364 in the early phase after transplantation. Histologic evaluation revealed the protective effects of CPSI-2364 treatment by a significantly less destruction of mucosal integrity at all time points. Perioperative treatment with CPSI-2364 improves graft motor function through impaired inflammatory responses to ischemia reperfusion injury by inhibition of proinflammatory cytokines and suppression of nitric oxide production in macrophages. CPSI-2364 presents as a promising complementary pharmacological approach preventing postoperative dysmotility for clinical intestinal transplantation.

Cell fusion phenomena detected after in utero transplantation of Ds-red-harboring porcine amniotic fluid stem cells into EGFP transgenic mice.

PubMed

Peng, Shao-Yu; Chen, Yu-Hsu; Chou, Chih-Jen; Wang, Yao-Horng; Lee, Hung-Maan; Cheng, Winston Teng-Kui; Shaw, S W Steven; Wu, Shinn-Chih

2014-05-01

Amniotic fluid stem cells (AFSCs) are derived from the amniotic fluid of the developing fetus and can give rise to diverse differentiated cells of ectoderm, mesoderm, and endoderm lineages. Intrauterine transplantation is an approach used to cure inherited genetic fetal defects during the gestation period of pregnant dams. Certain disease such as osteogenesis imperfecta was successfully treated in affected fetal mice using this method. However, the donor cell destiny remains uncertain. The purpose of this study was to investigate the biodistribution and cell fate of Ds-red-harboring porcine AFSCs (Ds-red pAFSCs) after intrauterine transplantation into enhanced green fluorescent protein-harboring fetuses of pregnant mice. Pregnant mice (12.5 days) underwent open laparotomy with intrauterine pAFSC transplantation (5 × 10(4) cells per pup) into fetal peritoneal cavity. Three weeks after birth, the mice were sacrificed. Several samples from different organs were obtained for histological examination and flow cytometric analysis. Ds-red pAFSCs migrated most frequently into the intestines. Furthermore, enhanced green fluorescent protein and red fluorescent protein signals were co-expressed in the intestine and liver cells via immunohistochemistry studies. In utero xenotransplantation of pAFSCs fused with recipient intestinal cells instead of differentiating or maintaining the undifferentiated status in the tissue. © 2014 John Wiley & Sons, Ltd.

Impaired intestinal mucosal barrier upon ischemia-reperfusion: "patching holes in the shield with a simple surgical method".

PubMed

Rosero, Olivér; Ónody, Péter; Kovács, Tibor; Molnár, Dávid; Lotz, Gábor; Tóth, Szilárd; Turóczi, Zsolt; Fülöp, András; Garbaisz, Dávid; Harsányi, László; Szijártó, Attila

2014-01-01

Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF- α levels were significantly lower in the PC-group compared to the IR-group. The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response.

The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease.

PubMed

Tang, Zeli; Shang, Mei; Chen, Tingjin; Ren, Pengli; Sun, Hengchang; Qu, Hongling; Lin, Zhipeng; Zhou, Lina; Yu, Jinyun; Jiang, Hongye; Zhou, Xinyi; Li, Xuerong; Huang, Yan; Xu, Jin; Yu, Xinbing

2016-12-19

Clonorchiasis, a food-borne zoonosis, is caused by Clonorchis sinensis. The intestinal tract and bile ducts are crucial places for C. sinensis metacercariae to develop into adult worms. The endospore of Bacillus subtilis is an ideal oral immunization vehicle for delivery of heterologous antigens to intestine. Cysteine protease of C. sinensis (CsCP) is an endogenous key component in the excystment of metacercariae and other physiological or pathological processes. We constructed a fusion gene of CotC (a coat protein)-CsCP and obtained B. subtilis spores with recombinant plasmid of pEB03-CotC-CsCP (B.s-CotC-CsCP). CotC-CsCP expressed on spores' surface was detected by Western blotting and immunofluorescence. Immunological characteristics of recombinant spore coat protein were evaluated in a mouse model. The levels of CsCP-specific antibodies were detected by ELISA. Effects of recombinant spores on mouse intestine were evaluated by histological staining. The activities of biochemical enzymes in serum were assayed by microplate. Liver sections of infected mice were evaluated by Ishak score after Masson's trichrome. The B.s-CotC-CsCP spores displayed CsCP on their coat. Specific IgG and isotypes were significantly induced by coat proteins of B.s-CotC-CsCP spores after subcutaneous immunization. IgA levels in intestinal mucus and bile of B.s-CotC-CsCP orally treated mice significantly increased. Additionally, more IgA-secreting cells were observed in enteraden and lamina propria regions of the mouse jejunum, and an increased amount of acidic mucins in intestines were also observed. There were no significant differences in enzyme levels of serum among groups. No inflammatory injury was observed in the intestinal tissues of each group. The degree of liver fibrosis was significantly reduced after oral immunization with B.s-CotC-CsCP spores. Bacillus subtilis spores maintained the original excellent immunogenicity of CsCP expressed on their surface. Both local and systemic specific immune responses were elicited by oral administration of B.s-CotC-CsCP spores. The spores effectively promoted intestinal health by inducing secretion of acidic mucins, with no other side effects to the liver or intestine. Oral administration of spores expressing CsCP could provide effective protection against C. sinensis. This study may be a cornerstone for development of antiparasitic agents or vaccines against clonorchiasis based on B. subtilis spore expressing CsCP on the surface.

Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

PubMed

Tuncyurek, P; Sari, M; Firat, O; Mutaf, I; Gulter, C; Tunger, A; Yuce, G; Yilmaz, M; Makay, O; Dayangac, M; Ersin, S

2006-01-01

Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model. Copyright 2006 S. Karger AG, Basel.

Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

PubMed

Grübel, P; Hoffman, J S; Chong, F K; Burstein, N A; Mepani, C; Cave, D R

1997-06-01

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori.

Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

PubMed Central

Grübel, P; Hoffman, J S; Chong, F K; Burstein, N A; Mepani, C; Cave, D R

1997-01-01

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori. PMID:9163433

GLNE 003: Preliminary Validation of Biomarkers Predictive of Barrett’s Esophagus Progression to Dysplasia and Adenocarcinoma — EDRN Public Portal

Cancer.gov

   Recognizing that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient, and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research program that provides the structure for validating and discovering potential surrogate endpoint biomarkers (“biomarkers”). Although examples of such biomarkers are currently in clinical use (i.e. CEA, CA-125), there are limitations to all of them. Our consortium focuses specifically on gastrointestinal neoplasia.    There are three goals for this phase of the proposed research. 1. Establish the feasibility of measuring the biomarkers in a multi-center clinical trial. 2. Estimate the variance of the biomarkers in cohorts defined by sex, race, age and histologic diagnosis (non-Barrett’s controls, Barrett’s intestinal metaplasia, Barrett’s intestinal dysplasia [low and high-grade] and adenocarcinoma). 3. Determine if the distributions of the biomarkers differ significantly among patients with different histologic diagnoses.    In this protocol, biological samples will consist of serum, plasma, urine, and biopsies from Barrett’s esophagus (metaplasia, low and high-grade dysplasia) patients, from patients with esophageal adenocarcinoma, and from non-Barrett’s controls. Samples will be assayed for villin, p53, Hsp27, cyclooxygenase-2, and Cyclin D1. Samples will also be used for two biomarker discovery projects, one exploring genetic expression using genomic microarrays and a second using two-dimensional gene arrays to discover and characterize amplified proteins associated with esophageal carcinogenesis. Fifty subjects will

Dietary Lactobacillus acidophilus positively influences growth performance, gut morphology, and gut microbiology in rurally reared chickens.

PubMed

Forte, C; Manuali, E; Abbate, Y; Papa, P; Vieceli, L; Tentellini, M; Trabalza-Marinucci, M; Moscati, L

2018-03-01

In a market undergoing constant evolution, the production of chicken meat that consumers would perceive as "natural" and "animal friendly" is crucial. The use of probiotics in rurally reared chickens could represent a major opportunity to achieve mutual benefit for both the industry and consumers. A total of 264 male Kabir chicks were randomly distributed to one of 2 dietary treatments: the L group received a commercial feed supplemented with 2.0 g/100 kg of Lactobacillus acidophilus D2/CSL, while the C group received the same basal diet without the additive. To assess the effects of probiotic supplementation in the chickens' diet, productive performance was evaluated at d 21 and 42, whereas microbiological analyses of the intestinal content and intestinal histology and morphometry were performed at the end of the trial (d 42). At d 21 and 42, L birds showed better (P < 0.001) performance in terms of body weight, average daily gain, and feed conversion ratio. Enterococci, staphylococci, and Escherichia coli populations were not influenced by dietary treatment. On the contrary, Lactobacillus population increased (P = 0.032) in the L group. Furthermore, a tendency (P = 0.069) was observed for the coliforms to be influenced by diet, with lower values in the L group in comparison to the C group. Histological techniques revealed that the number of goblet cell containing neutral mucins was lower in the C group. Morphometric evaluations demonstrated that the probiotic supplementation increased the height of the mucosal layer by improving (P = 0.040) villus height, while crypt depth was unaffected. In conclusion, the results obtained in this study demonstrate that it is possible to use Lactobacillus acidophilus D2/CSL (CECT 4529) in rurally reared chicken breeds with positive effects on performance and gut health.

Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma

PubMed Central

Cheng, Hsin-Hung; Tseng, Guan-Ying; Yang, Hsiao-Bai; Wang, Hung-Jung; Lin, Hwai-Jeng; Wang, Wen-Ching

2012-01-01

AIM: To determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis, peptic ulcers and gastric cancer. METHODS: This study was a retrospective analysis of gastric antrum biopsy specimens from healthy controls (n = 22) and patients with gastritis (n = 30), peptic ulcer (n = 83), or gastric cancer (n = 32). Expression of CD4, CD25 and Foxp3 was determined by immunohistochemistry in three consecutive sections per sample. RESULTS: Compared with healthy controls, there was an increased number of CD25+ and Foxp3+ cells in patients with gastritis (P = 0.004 and P = 0.008), peptic ulcer (P < 0.001 and P < 0.001), and gastric cancer (P < 0.001 and P < 0.001). The ratio of CD25+/CD4+ or Foxp3+/CD4+ cells was also significantly higher in all disease groups (P < 0.001, respectively). The number of CD4+, CD25+, and Foxp3+ cells, and the ratio of CD25+/CD4+ and Foxp3+/CD4+ cells, were associated with the histological grade of the specimens, including acute inflammation, chronic inflammation, lymphoid follicle number, and Helicobacter pylori infection. The number of CD4+, CD25+ and Foxp3+ cells, and the ratio of CD25+/CD4+ and Foxp3+/CD4+ cells, were negatively associated with intestinal metaplasia among gastritis (P < 0.001, P < 0.001, P < 0.001, P = 0.002 and P = 0.002) and peptic ulcer groups (P = 0.013, P = 0.004, P < 0.001, P = 0.040 and P = 0.003). CONCLUSION: Tregs are positively associated with endoscopic findings of gastroduodenal diseases and histological grade but negatively associated with intestinal metaplasia in gastritis and peptic ulcer groups. PMID:22228968

Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

PubMed

Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

2006-01-01

Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Lin; Department of Pharmacology, University of Nantong, Nantong; Chen, Yeru

Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative in food, food packaging and medicines. Its chemopreventive properties are attributing to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. This study was to investigate the histological changes of Nrf2 and its regulated phase II enzymes Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2{sup −/−} mice induced by BHA. The mice were given a 200 mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from WTmore » mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region. In contrast, the induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly identical to that of Nrf2, with more intense staining in the villus than that the crypt. Conversely, Keap1 was more highly expressed in the crypt, where the proliferative cells reside. Our study demonstrates that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine from WT but not Nrf2{sup −/−} mice, demonstrating a cell type specific response to BHA in vivo. - Highlights: • Histological view of basal and inducible Nrf2 and its targets in vivo • Induction of detoxification enzymes by BHA is cell-type dependent. • BHA induces the expression of HO-1 in Kupffer cells.« less

A Gnotobiotic Pig Model for Determining Human Norovirus Inactivation by High-Pressure Processing

PubMed Central

Lou, Fangfei; Ye, Mu; Ma, Yuanmei; Li, Xinhui; DiCaprio, Erin; Chen, Haiqiang; Krakowka, Steven; Hughes, John; Kingsley, David

2015-01-01

Human norovirus (NoV) is responsible for over 90% of outbreaks of acute nonbacterial gastroenteritis worldwide and accounts for 60% of cases of foodborne illness in the United States. Currently, the infectivity of human NoVs is poorly understood due to the lack of a cell culture system. In this study, we determined the survival of a human NoV genogroup II, genotype 4 (GII.4) strain in seeded oyster homogenates after high-pressure processing (HPP) using a novel receptor binding assay and a gnotobiotic pig model. Pressure conditions of 350 MPa at 0°C for 2 min led to a 3.7-log10 reduction in the number of viral RNA copies in oysters, as measured by the porcine gastric mucin-conjugated magnetic bead (PGM-MB) binding assay and real-time RT-PCR, whereas pressure conditions of 350 MPa at 35°C for 2 min achieved only a 1-log10 reduction in the number of RNA copies. Newborn gnotobiotic piglets orally fed oyster homogenate treated at 350 MPa and 0°C for 2 min did not have viral RNA shedding in feces, histologic lesions, or viral replication in the small intestine. In contrast, gnotobiotic piglets fed oysters treated at 350 MPa and 35°C for 2 min had high levels of viral shedding in feces and exhibited significant histologic lesions and viral replication in the small intestine. Collectively, these data demonstrate that (i) human NoV survival estimated by an in vitro PGM-MB virus binding assay is consistent with the infectivity determined by an in vivo gnotobiotic piglet model and (ii) HPP is capable of inactivating a human NoV GII.4 strain at commercially acceptable pressure levels. PMID:26187968