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Sample records for spontaneously develop colitis

  1. Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

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    Vendramini-Costa, Débora Barbosa, E-mail: vendramini.debora@gmail.com [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Alcaide, Antonio [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Pelizzaro-Rocha, Karin Juliane [Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, SP (Brazil); Talero, Elena; Ávila-Román, Javier [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Garcia-Mauriño, Sofia [Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Seville (Spain); Pilli, Ronaldo Aloise [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Carvalho, João Ernesto de [Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP (Brazil); Motilva, Virginia [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain)

    2016-06-01

    Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1 expression

  2. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.

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    Chad K Heazlewood

    2008-03-01

    Full Text Available MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p < 0.01 and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1beta, TNF-alpha, and IFN-gamma was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-gamma, TNF-alpha, and IL-13. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar

  3. A novel murine model of inflammatory bowel disease and inflammation-associated colon cancer with ulcerative colitis-like features.

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    Laura P Hale

    Full Text Available Mutations that increase susceptibility to inflammatory bowel disease (IBD have been identified in a number of genes in both humans and mice, but the factors that govern how these mutations contribute to IBD pathogenesis and result in phenotypic presentation as ulcerative colitis (UC or Crohn disease (CD are not well understood. In this study, mice deficient in both TNF and IL-10 (T/I mice were found to spontaneously develop severe colitis soon after weaning, without the need for exogenous triggers. Colitis in T/I mice had clinical and histologic features similar to human UC, including a markedly increased risk of developing inflammation-associated colon cancer. Importantly, development of spontaneous colitis in these mice was prevented by antibiotic treatment. Consistent with the known role of Th17-driven inflammation in response to bacteria, T/I mice had elevated serumTh17-type cytokines when they developed spontaneous colitis and after systemic bacterial challenge via NSAID-induced degradation of the mucosal barrier. Although TNF production has been widely considered to be be pathogenic in IBD, these data indicate that the ability to produce normal levels of TNF actually protects against the spontaneous development of colitis in response to intestinal colonization by bacteria. The T/I mouse model will be useful for developing new rationally-based therapies to prevent and/or treat IBD and inflammation-associated colon cancer and may further provide important insights into the pathogenesis of UC in humans.

  4. Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

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    Anna Pérez-Bosque

    Full Text Available Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT. Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT mice and mice lacking the mdr1a gene (KO were fed diets supplemented with either SBI (2% w/w or milk proteins (Control diet, from day 21 (weaning until day 56. Leucocytes in mesenteric lymph nodes (MLN and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05. The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05 and SBI supplementation reduced this variable (p < 0.05. The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05. In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold, IL-6 (26-fold and IL-17 (19-fold, and of chemokines MIP-1β (4.5-fold and MCP-1 (7.2-fold. These effects were significantly prevented by SBI (p < 0.05. SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

  5. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility.

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    Joshua M Uronis

    2009-06-01

    Full Text Available It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD and ulcerative colitis (UC collectively referred to as inflammatory bowel disease (IBD. Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC. However, the impact of the microbiota on the development of colitis-associated cancer (CAC remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM-exposed, conventionalized-Il10(-/- mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62% of AOM-Il10(-/- mice developed colon tumors compared to only 3/15 (20% of AOM- wild-type (WT mice. Conventionalized AOM-Il10(-/- mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10(-/- mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10(-/- mice. Germ-free AOM-treated Il10(-/- mice showed normal colon histology and were devoid of tumors. Il10(-/-; Myd88(-/- mice treated with AOM displayed reduced expression of Il12p40 and Tnfalpha mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma.

  6. Development of chronic colitis is dependent on the cytokine MIF.

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    de Jong, Y P; Abadia-Molina, A C; Satoskar, A R; Clarke, K; Rietdijk, S T; Faubion, W A; Mizoguchi, E; Metz, C N; Alsahli, M; ten Hove, T; Keates, A C; Lubetsky, J B; Farrell, R J; Michetti, P; van Deventer, S J; Lolis, E; David, J R; Bhan, A K; Terhorst, C; Sahli, M A

    2001-11-01

    The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

  7. Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

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    Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

    2016-04-05

    Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

  8. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis.

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    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-06-30

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

  9. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis

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    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-01-01

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recogni...

  10. B cells exposed to enterobacterial components suppress development of experimental colitis

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    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    ). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

  11. Reduction of colitis by prebiotics in HLA-1327 transgenic rats is associated with microflora changes and immunomodulation

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    Hoentjen, F; Welling, GW; Harmsen, HJM; Zhang, XY; Snart, J; Tannock, GW; Lien, K; Churchill, TA; Lupicki, M; Dieleman, LA

    HLA-B27 transgenic rats develop spontaneous colitis under specific pathogen-free conditions (SPF) but germ-free rats remain disease-free, emphasizing a role for intestinal bacteria in the pathogenesis of chronic intestinal inflammation. Prebiotics are dietary substances that affect the host by

  12. Sequestering HMGB1 via DNA-Conjugated Beads Ameliorates Murine Colitis

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    Antoine, Daniel J.; Dancho, Meghan; Tsaava, Teá; Li, Jianhua; Lu, Ben; Levine, Yaakov A.; Stiegler, Andrew; Tamari, Yehuda; Al-Abed, Yousef; Roth, Jesse; Tracey, Kevin J.; Yang, Huan

    2014-01-01

    Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that affects millions of people worldwide. Although the etiology of IBD is not clear, it is known that products from stressed cells and enteric microbes promote intestinal inflammation. High mobility group box 1 (HMGB1), originally identified as a nuclear DNA binding protein, is a cytokine-like protein mediator implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated levels of HMGB1 have been detected in inflamed human intestinal tissues and in feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by administration of anti-HMGB1 antibodies or HMGB1-specific antagonist improves clinical outcomes in animal models of colitis. Since HMGB1 binds to DNA with high affinity, here we developed a novel strategy to sequester HMGB1 using DNA immobilized on sepharose beads. Screening of DNA-bead constructs revealed that B2 beads, one linear form of DNA conjugated beads, bind HMGB1 with high affinity, capture HMGB1 ex vivo from endotoxin-stimulated RAW 264.7 cell supernatant and from feces of mice with colitis. Oral administration of B2 DNA beads significantly improved body weight, reduced colon injury, and suppressed colonic and circulating cytokine levels in mice with spontaneous colitis (IL-10 knockout) and with dextran sulfate sodium-induced colitis. Thus, DNA beads reduce inflammation by sequestering HMGB1 and may have therapeutic potential for the treatment of IBD. PMID:25127031

  13. Development of perianal ulcer as a result of acute fulminant amoebic colitis.

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    Torigoe, Takayuki; Nakayama, Yoshifumi; Yamaguchi, Koji

    2012-09-14

    We report a case of acute fulminant amoebic colitis that resulted in the development of a perianal ulcer in a 29-year-old Japanese homosexual man with acquired immunodeficiency syndrome (AIDS). The patient was admitted to our hospital with a persistent perianal abscess that was refractory to antibiotic therapy administered at another hospital. On admission, we observed a giant ulcer in the perianal region. At first, cytomegalovirus colitis was suspected by blood investigations. Ganciclovir therapy was initiated; however, the patient developed necrosis of the skin around the anus during therapy. We only performed end-sigmoidostomy and necrotomy to avoid excessive surgical invasion. Histopathological examination of the surgical specimen revealed the presence of trophozoite amoebae, indicating a final diagnosis of acute fulminant amoebic colitis. The patient's postoperative course was favorable, and proctectomy of the residual rectum was performed 11 mo later. Amoebic colitis is one of the most severe complications affecting patients with AIDS. Particularly, acute fulminant amoebic colitis may result in a poor prognosis; therefore, staged surgical therapy as a less invasive procedure should be considered as one of the treatment options for these patients.

  14. The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

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    Aleksandra Matuszyk

    2015-01-01

    Full Text Available Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS. Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin’s anti-inflammatory and antioxidative properties.

  15. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis.

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    Shailubhai, Kunwar; Palejwala, Vaseem; Arjunan, Krishna Priya; Saykhedkar, Sayali; Nefsky, Bradley; Foss, John A; Comiskey, Stephen; Jacob, Gary S; Plevy, Scott E

    2015-11-06

    To evaluate the effect of orally administered plecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models. The cyclic guanosine monophosphate (cGMP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cell-based assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid (5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium (DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic (TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout (TCRα(-/-)) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity. Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C (GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cGMP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs (0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity (P < 0.05) and disease activity index (P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα(-/-) mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. This is the first-ever study reporting

  16. Simultaneous development of ulcerative colitis in the colon and sigmoid neovagina.

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    Webster, Toni; Appelbaum, Heather; Weinstein, Toba A; Rosen, Nelson; Mitchell, Ian; Levine, Jeremiah J

    2013-03-01

    Vaginoplasty using sigmoid colon is a common technique for creation of a neovagina. However, special consideration must be given to potential long term consequences of using a colonic conduit for vaginal replacement. We report on the youngest described case in which a patient developed ulcerative colitis refractory to medical therapy with simultaneous involvement of a sigmoid neovagina requiring total proctocolectomy and neovaginectomy. A 17 year old XY female with a history of gonadal dysgenesis and sigmoid graft vaginoplasty presented with a history of bloody, mucoid vaginal discharge, abdominal pain, bloody diarrhea and weight loss. Colonic and neovaginal biopsies demonstrated active colitis with diffuse ulcerations, consistent with ulcerative colitis. Despite aggressive immunosuppressive treatment she had persistent neovaginal and colonic bleeding requiring multiple transfusions, subtotal colectomy and ultimately completion proctectomy and neovaginectomy. It is imperative to recognize that colectomy alone may be an inadequate surgical intervention in patients with ulcerative colitis and a colonic neovaginal graft and that a concomitant neovaginectomy may be integral in providing appropriate treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. MicroRNA214 Is Associated With Progression of Ulcerative Colitis, and Inhibition Reduces Development of Colitis and Colitis-Associated Cancer in Mice.

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    Polytarchou, Christos; Hommes, Daniel W; Palumbo, Tiziana; Hatziapostolou, Maria; Koutsioumpa, Marina; Koukos, Georgios; van der Meulen-de Jong, Andrea E; Oikonomopoulos, Angelos; van Deen, Welmoed K; Vorvis, Christina; Serebrennikova, Oksana B; Birli, Eleni; Choi, Jennifer; Chang, Lin; Anton, Peter A; Tsichlis, Philip N; Pothoulakis, Charalabos; Verspaget, Hein W; Iliopoulos, Dimitrios

    2015-10-01

    Persistent activation of the inflammatory response contributes to the development of inflammatory bowel diseases, which increase the risk of colorectal cancer. We aimed to identify microRNAs that regulate inflammation during the development of ulcerative colitis (UC) and progression to colitis-associated colon cancer (CAC). We performed a quantitative polymerase chain reaction analysis to measure microRNAs in 401 colon specimens from patients with UC, Crohn's disease, irritable bowel syndrome, sporadic colorectal cancer, or CAC, as well as subjects without these disorders (controls); levels were correlated with clinical features and disease activity of patients. Colitis was induced in mice by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by addition of azoxymethane; some mice also were given an inhibitor of microRNA214 (miR214). A high-throughput functional screen of the human microRNAome found that miR214 regulated the activity of nuclear factor-κB. Higher levels of miR214 were detected in colon tissues from patients with active UC or CAC than from patients with other disorders or controls and correlated with disease progression. Bioinformatic and genome-wide profile analyses showed that miR214 activates an inflammatory response and is amplified through a feedback loop circuit mediated by phosphatase and tensin homolog (PTEN) and PDZ and LIM domain 2 (PDLIM2). Interleukin-6 induced signal transducer and activator of transcription 3 (STAT3)-mediated transcription of miR214. A miR214 chemical inhibitor blocked this circuit and reduced the severity of DSS-induced colitis in mice, as well as the number and size of tumors that formed in mice given azoxymethane and DSS. In fresh colonic biopsy specimens from patients with active UC, the miR214 inhibitor reduced inflammation by increasing levels of PDLIM2 and PTEN. Interleukin-6 up-regulates STAT3-mediated transcription of miR214 in colon tissues, which reduces levels of PDLIM2 and PTEN

  18. Hemidesmosome integrity protects the colon against colitis and colorectal cancer.

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    De Arcangelis, Adèle; Hamade, Hussein; Alpy, Fabien; Normand, Sylvain; Bruyère, Emilie; Lefebvre, Olivier; Méchine-Neuville, Agnès; Siebert, Stéphanie; Pfister, Véronique; Lepage, Patricia; Laquerriere, Patrice; Dembele, Doulaye; Delanoye-Crespin, Anne; Rodius, Sophie; Robine, Sylvie; Kedinger, Michèle; Van Seuningen, Isabelle; Simon-Assmann, Patricia; Chamaillard, Mathias; Labouesse, Michel; Georges-Labouesse, Elisabeth

    2017-10-01

    Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the α6β4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM. We developed new mouse models inducing IEC-specific ablation of α6 integrin either during development (α6 ΔIEC ) or in adults (α6 ΔIEC-TAM ). Strikingly, all α6 ΔIEC mutant mice spontaneously developed long-standing colitis, which degenerated overtime into infiltrating adenocarcinoma. The sequence of events leading to disease onset entails hemidesmosome disruption, BM detachment, IL-18 overproduction by IECs, hyperplasia and enhanced intestinal permeability. Likewise, IEC-specific ablation of α6 integrin induced in adult mice (α6 ΔIEC-TAM ) resulted in fully penetrant colitis and tumour progression. Whereas broad-spectrum antibiotic treatment lowered tissue pathology and IL-1β secretion from infiltrating myeloid cells, it failed to reduce Th1 and Th17 response. Interestingly, while the initial intestinal inflammation occurred independently of the adaptive immune system, tumourigenesis required B and T lymphocyte activation. We provide for the first time evidence that loss of IECs/BM interactions triggered by hemidesmosome disruption initiates the development of inflammatory lesions that progress into high-grade dysplasia and carcinoma. Colorectal neoplasia in our mouse models resemble that seen in patients with IBD, making them highly attractive for discovering more efficient therapies. Published by the BMJ Publishing Group Limited. For permission to use (where

  19. Sequential changes in luminal microflora and mucosal cytokine expression during developing of colitis in HLA-B27/beta2-microglobulin transgenic rats.

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    Hata, K; Andoh, A; Sato, H; Araki, Y; Tanaka, M; Tsujikawa, T; Fujiyama, Y; Bamba, T

    2001-11-01

    Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model. HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods. Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period. The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

  20. Development of chronic colitis is dependent on the cytokine MIF

    NARCIS (Netherlands)

    de Jong, Y. P.; Abadia-Molina, A. C.; Satoskar, A. R.; Clarke, K.; Rietdijk, S. T.; Faubion, W. A.; Mizoguchi, E.; Metz, C. N.; Alsahli, M.; ten Hove, T.; Keates, A. C.; Lubetsky, J. B.; Farrell, R. J.; Michetti, P.; van Deventer, S. J.; Lolis, E.; David, J. R.; Bhan, A. K.; Terhorst, C.; Sahli, M. A.

    2001-01-01

    The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis.

  1. Colitis ulcerosa

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Jess, Tine; Bjerrum, Jacob Tveiten

    2013-01-01

    Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of th......Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer...... is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive...

  2. Two for One: Coexisting Ulcerative Colitis and Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Grant I Chen

    2002-01-01

    Full Text Available Three cases of coexisting ulcerative colitis and Crohn’s disease are presented. In the first case, the patient had a long-standing history of ulcerative proctitis before developing Crohn’s colitis. In the two remaining cases, the patients presented initially with Crohn’s disease of the ileum and, subsequent to resection, developed ulcerative colitis. Well-documented cases of patients diagnosed with both ulcerative colitis and Crohn’s disease are rare. The literature on such cases is reviewed, and the controversy over whether ulcerative colitis and Crohn’s disease are two distinct diseases is explored.

  3. Non-IBD and noninfectious colitis

    DEFF Research Database (Denmark)

    Nielsen, O.H.; Vainer, B.; Rask-Madsen, J.

    2008-01-01

    , diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases. Most of these diseases are uncommon; therefore, epidemiologic data and data from controlled...

  4. Malignant change of chronic ulcerative colitis: report of a case

    International Nuclear Information System (INIS)

    Kim, Ki Tae; Lee, Han Jin; Kang, Si Won; Bahk, Yong Whee

    1988-01-01

    Since the original report of Crohn and Rosenberg (1928) the association between long-standing ulcerative colitis and later development of colonic malignancy has been well known. There are many risk factors for the development of malignancy such as duration, extent, severity and age of the onset of ulcerative colitis, drugs and diagnostic radiation. The dysplasia of the colonic mucosa as a precancerous change are seen not only in the area of malignant focus but also in distant locations in long-standing ulcerative colitis. We present a case of malignant change occurred in a patient with long-standing ulcerative colitis in the rectosigmoid junction. This is probably the first documentation of malignant transformation of ulcerative colitis in the Korean literature.

  5. Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer

    International Nuclear Information System (INIS)

    Maeda, Shin; Hikiba, Yohko; Shibata, Wataru; Ohmae, Tomoya; Yanai, Ayako; Ogura, Keiji; Yamada, Shingo; Omata, Masao

    2007-01-01

    High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-κB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-κB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer

  6. Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice

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    Marco Constante

    2017-09-01

    Full Text Available Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD, where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis

  7. Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-gamma Activity

    DEFF Research Database (Denmark)

    Pedersen, G.; Brynskov, Jørn

    2010-01-01

    and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone (a PPAR gamma ligand) in patients with ulcerative colitis. METHODS: Spontaneous and rosiglitazone-mediated PPAR gamma and adipophillin expression (a gene transcriptionally activated by PPAR...... for 14 days. RESULTS: PPAR gamma expression was fourfold reduced in epithelial cells from inflamed compared with uninflamed mucosa and controls. Adipophillin levels were decreased in parallel. Rosiglitazone induced a concentration-dependent increase in adipophillin levels and restored PPAR gamma activity...... in epithelial cells from inflamed mucosa in vitro. Rosiglitazone enema treatment was well tolerated and reduced the Mayo ulcerative colitis score from 8.9 to 4.3 (P levels in the epithelial cells of the patients, indicating PPAR...

  8. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse

    Science.gov (United States)

    Arrieta, M C; Madsen, K; Doyle, J; Meddings, J

    2008-01-01

    Background: Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some models of disease increased permeability appears to be a very early event. The interleukin 10 (IL10) gene-deficient mouse spontaneously develops colitis after 12 weeks of age. These mice have been shown to have increased small intestinal permeability that appears early in life. Furthermore, the development of colitis is dependent upon luminal agents, as animals do not develop disease if raised under germ-free conditions. Aims: To determine if the elevated small bowel permeability can be prevented, and if by doing so colonic disease is prevented or attenuated. Methods: IL10 gene-deficient (IL10−/−) mice) were treated with AT-1001 (a zonulin peptide inhibitor), a small peptide previously demonstrated to reduce small intestinal permeability. Small intestinal permeability was measured, in vivo, weekly from 4 to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers, and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured in the colon. Colonic permeability and histology were also endpoints. Results: Treated animals showed a marked reduction in small intestinal permeability. Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there was a significant reduction of colonic mucosal permeability and increased electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor α (TNFα) from a colonic explant was significantly lower in the treated group (25.33 (SE 4.30) pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All other markers also demonstrated a clear reduction of colitis in the treated animals. Additional experiments were performed which demonstrated that AT-1001 was functionally active only in the small

  9. Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

    Science.gov (United States)

    Kim, Han-Byul; Kim, Minchul; Park, Young-Soo; Park, Intae; Kim, Tackhoon; Yang, Sung-Yeun; Cho, Charles J; Hwang, DaeHee; Jung, Jin-Hak; Markowitz, Sanford D; Hwang, Sung Wook; Yang, Suk-Kyun; Lim, Dae-Sik; Myung, Seung-Jae

    2017-02-01

    developed colitis after administration of DSS, but injection of PGE 2 led to colon regeneration in these mice. However, YAP-knockout mice did not regenerate colon tissues and died soon after administration of DSS. 15-PGDH-knockout mice regenerated colon tissues more rapidly than control mice after withdrawal of DSS, and had faster recovery of body weight, colon length, and colitis histology scores. These effects were reversed by injection of indomethacin. SAV1-knockout or 15-PGDH-knockout mice did not develop spontaneous tumors after colitis induction, but SAV1/15-PGDH double-knockout mice developed polyps that eventually progressed to carcinoma in situ. Administration of indomethacin to these mice prevented spontaneous tumor formation. Levels of PGE 2 correlated with those of YAP levels in human sporadic colorectal tumors and colitis-associated tumors. PGE 2 signaling increases the expression and transcriptional activities of YAP1, leading to increased expression of cyclooxygenase 2 and EP4 to activate a positive signaling loop. This pathway promotes proliferation of colon cancer cell lines and colon tissue regeneration in mice with colitis. Constitutive activation of this pathway led to formation of polyps and colon tumors in mice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Colitis of Behcet's syndrome

    International Nuclear Information System (INIS)

    O'Connell, D.J.; Courtney, J.V.; Riddell, R.H.

    1980-01-01

    Three patients with Behcet's syndrome and colitis are described. The radiologic and histologic appearances of the colitis are discussed. The similarities of Behcet's colitis to Crohn's disease are outlined. The cases demonstrate the necessity to consider Behcet's syndrome in the differential diagnosis of inflammatory bowel disease. (orig.) [de

  11. Long-Term Natural History and Complications of Collagenous Colitis

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2012-01-01

    Full Text Available Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal ‘dissection’, colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids. Finally, lymphoproliferative disease has been reported.

  12. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation......One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses......-driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers...

  13. Calcineurin B in CD4+ T Cells Prevents Autoimmune Colitis by Negatively Regulating the JAK/STAT Pathway.

    Science.gov (United States)

    Mencarelli, Andrea; Vacca, Maurizio; Khameneh, Hanif Javanmard; Acerbi, Enzo; Tay, Alicia; Zolezzi, Francesca; Poidinger, Michael; Mortellaro, Alessandra

    2018-01-01

    Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically deleted in CD4 + T cells (Cnb1 CD4 mice) to delineate the role of the Cn-NFAT pathway in immune homeostasis of the intestine. The Cnb1 CD4 mice developed severe, spontaneous colitis characterized at the molecular level by an increased T helper-1-cell response but an unaltered regulatory T-cell compartment. Antibiotic treatment ameliorated the intestinal inflammation observed in Cnb1 CD4 mice, suggesting that the microbiota contributes to the onset of colitis. CD4 + T cells isolated from Cnb1 CD4 mice produced high levels of IFNγ due to increased activation of the JAK2/STAT4 pathway induced by IL-12. Our data highlight that Cn signaling in CD4 + T cells is critical for intestinal immune homeostasis in part by inhibiting IL-12 responsiveness of CD4 + T cells.

  14. Ulcerative colitis presenting as leukocytoclastic vasculitis of skin

    OpenAIRE

    Akbulut, Sabiye; Ozaslan, Ersan; Topal, Firdevs; Albayrak, Levent; Kayhan, Burcak; Efe, Cumali

    2008-01-01

    A number of cutaneous changes are known to occur in the course of inflammatory bowel diseases (IBD), including pyoderma gangrenosum, erythema nodosum, perianal disease, erythematous eruptions, urticaria, and purpura. However, occurrence of skin manifestations prior to the development of ulcerative colitis is a rare occasion. Here, we report a case of ulcerative colitis associated with leukocytoclastic vasculitis in which the intestinal symptoms became overt 8 mo after the development of skin ...

  15. Future targets for immune therapy in colitis?

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Claesson, M H

    2008-01-01

    Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against...... the commensal intestinal bacterial flora, and that the CD4+ T cells dominate the adaptive immune response. Chemokines are small proteins involved in the guidance of migration of immune cells during normal homeostasis and inflammation. Chemokines have been shown to play a central role in recruiting inflammatory...... cells from congenic normal mice are transplanted into immune deficient mice, which in turn develop a chronic lethal colitis within 1-2 months. By simultaneous transplantation of CD4+CD25+ regulatory T cells (Tregs) it is possible to hinder development of colitis. Thus the model is well suited...

  16. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  17. Fecal Microbiota and Metabolome in a Mouse Model of Spontaneous Chronic Colitis: Relevance to Human Inflammatory Bowel Disease.

    Science.gov (United States)

    Robinson, Ainsley M; Gondalia, Shakuntla V; Karpe, Avinash V; Eri, Rajaraman; Beale, David J; Morrison, Paul D; Palombo, Enzo A; Nurgali, Kulmira

    2016-12-01

    Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD. The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry. Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids. Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.

  18. Ulcerative colitis presenting as leukocytoclastic vasculitis of skin.

    Science.gov (United States)

    Akbulut, Sabiye; Ozaslan, Ersan; Topal, Firdevs; Albayrak, Levent; Kayhan, Burcak; Efe, Cumali

    2008-04-21

    A number of cutaneous changes are known to occur in the course of inflammatory bowel diseases (IBD), including pyoderma gangrenosum, erythema nodosum, perianal disease, erythematous eruptions, urticaria, and purpura. However, occurrence of skin manifestations prior to the development of ulcerative colitis is a rare occasion. Here, we report a case of ulcerative colitis associated with leukocytoclastic vasculitis in which the intestinal symptoms became overt 8 mo after the development of skin lesions.

  19. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis

    Science.gov (United States)

    Phadke, Varun K.; Friedman-Moraco, Rachel J.; Quigley, Brian C.; Farris, Alton B.; Norvell, J. P.

    2016-01-01

    Abstract Background: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. Methods: We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. Results: A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Conclusions: Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease. PMID:27759636

  20. Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

    Science.gov (United States)

    Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

    2016-11-01

    Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

  1. Colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai in patients with ulcerative colitis: a report of two cases.

    Science.gov (United States)

    Kondo, Satoru; Araki, Toshimitsu; Okita, Yoshiki; Yamamoto, Akira; Hamada, Yasuhiko; Katsurahara, Masaki; Horiki, Noriyuki; Nakamura, Misaki; Shimoyama, Takahiro; Yamamoto, Takayuki; Takei, Yoshiyuki; Kusunoki, Masato

    2018-03-16

    Orally administered Qing-dai, called indigo naturalis in Latin, is reportedly useful for the treatment of ulcerative colitis. We herein describe two patients with ulcerative colitis who developed colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai. In Case 1, a 35-year-old man developed colitis similar to ischemic colitis with bloody stool that recurred each time he ingested Qing-dai. He had no signs of recurrence upon withdrawal of Qing-dai. In Case 2, a 43-year-old woman underwent ileocecal resection for treatment of an intussusception 2 months after beginning oral administration of Qing-dai. Edema and congestion but no ulceration were present in the mucosa of the resected specimen. Both patients exhibited abdominal pain with bloody diarrhea, and abdominal computed tomography showed marked wall edema affecting an extensive portion of the large bowel.

  2. Spontaneous Development of Moral Concepts

    Science.gov (United States)

    Siegal, M.

    1975-01-01

    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  3. Isolated naratriptan-associated ischemic colitis

    Science.gov (United States)

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  4. Stercoral colitis mimicking appendicitis

    Directory of Open Access Journals (Sweden)

    Abdelghafour Elkoundi

    2017-02-01

    Full Text Available Abstract Background Stercoral colitis is an inflammatory process involving the colonic wall related to fecal impaction. This rare condition is associated with high morbidity-mortality. Findings We report a case of a 78-year-old woman with a history of dementia under clozapine who presented a clinical and sonographic presentation of acute appendicitis. The worsening of her clinical condition prompted us to review our diagnosis and modify our approach using the CT scan which was consistent with stercoral colitis. This report concerns an atypical presentation of this condition. Conclusions The present case highlights the ability of severe forms of fecal impaction to precipitate very rare and life-threatening complications like stercoral colitis. It also points the importance of including stercoral colitis in the differential diagnosis of acute appendicitis in altered patients under anticholenergic drugs and the critical role of the CT scan as a crucial radiologic adjunct.

  5. Eosinophilic colitis in infants

    Directory of Open Access Journals (Sweden)

    Adriana Chebar Lozinsky

    2014-01-01

    Full Text Available OBJECTIVE: To review the literature for clinical data on infants with allergic or eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed using the words ''colitis or procto-colitis and eosinophilic'' or ''colitis or proctocolitis and allergic'' between 1966 and February of 2013. All articles that described patients' characteristics were selected. DATA SYNTHESIS: A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263 of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 perhigh-power field in 89.3% (236/264 of patients. Most patients showed improvement with theremoval of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients. CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow'smilk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure.

  6. An antibiotic-responsive mouse model of fulminant ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Silvia S Kang

    2008-03-01

    Full Text Available BACKGROUND: The constellation of human inflammatory bowel disease (IBD includes ulcerative colitis and Crohn's disease, which both display a wide spectrum in the severity of pathology. One theory is that multiple genetic hits to the host immune system may contribute to the susceptibility and severity of IBD. However, experimental proof of this concept is still lacking. Several genetic mouse models that each recapitulate some aspects of human IBD have utilized a single gene defect to induce colitis. However, none have produced pathology clearly distinguishable as either ulcerative colitis or Crohn's disease, in part because none of them reproduce the most severe forms of disease that are observed in human patients. This lack of severe IBD models has posed a challenge for research into pathogenic mechanisms and development of new treatments. We hypothesized that multiple genetic hits to the regulatory machinery that normally inhibits immune activation in the intestine would generate more severe, reproducible pathology that would mimic either ulcerative colitis or Crohn's disease. METHODS AND FINDINGS: We generated a novel mouse line (dnKO that possessed defects in both TGFbetaRII and IL-10R2 signaling. These mice rapidly and reproducibly developed a disease resembling fulminant human ulcerative colitis that was quite distinct from the much longer and more variable course of pathology observed previously in mice possessing only single defects. Pathogenesis was driven by uncontrolled production of proinflammatory cytokines resulting in large part from T cell activation. The disease process could be significantly ameliorated by administration of antibodies against IFNgamma and TNFalpha and was completely inhibited by a combination of broad-spectrum antibiotics. CONCLUSIONS: Here, we develop to our knowledge the first mouse model of fulminant ulcerative colitis by combining multiple genetic hits in immune regulation and demonstrate that the resulting

  7. Ulcerative colitis masked by giant urticaria.

    Science.gov (United States)

    Caroselli, C; Plocco, M; Pratticò, F; Bruno, C; Antonaglia, C; Rota, F; Curreli, I; Caroselli, A; Bruno, G

    2007-01-01

    The occurrence of giant urticaria and ulcerative colitis is very infrequent. A 23 year-old female reported the initial eruption of short-lived cutaneous itchy weals on her arms. Then lesions ran together and became confluent, extending to her legs, followed by undefined abdominal pain and a slight increase of body temperature. Exams showed hystologically confirmed ulcerative colitis, with perinuclear anti-neutrophil cytoplasmic antibody positivity. Ulcerative colitis therapy led not only to the remission of the colitic symptoms, but also to the prompt recovery of skin manifestations. Urticaria was the epiphenomenon of ulcerative colitis.

  8. Genetics Home Reference: ulcerative colitis

    Science.gov (United States)

    ... are some genetic conditions more common in particular ethnic groups? Genetic Changes A variety of genetic and environmental factors are likely involved in the development of ulcerative colitis . Recent studies have identified variations in dozens of genes that may be linked ...

  9. Radiologic findings in taxane induced colitis

    International Nuclear Information System (INIS)

    Kaur, Harmeet; Loyer, Evelyne M.; David, Cynthia L.; Sawaf, Hassan; DuBrow, Ronelle A.; Ibrahim, Nuhad K.

    2008-01-01

    Ischemic colitis in breast cancer patients being treated with taxane-based chemotherapy, which may lead to serious morbidities and even death, has recently been defined as a clinical entity. The purpose of this retrospective study was to evaluate the computed tomography (CT) findings in taxane-related colitis and determine their clinical relevance. CT scans of 41 patients at risk for taxane colitis were reviewed retrospectively for bowel and peritoneal abnormalities. Morphological findings were analyzed and correlated with clinical, pathological, and endoscopic findings. CT scans in 10 of the 41 patients showed a definitely abnormal colon with a thickened wall or distended with fluid, signs that are suggestive of colitis, in the context of the clinical picture. Radiographic changes in patients with taxane colitis are not specific but, in the appropriate context, can suggest the correct diagnosis and guide the patient's management

  10. Treatment of experimental colitis in mice with LMP-420, an inhibitor of TNF transcription

    Directory of Open Access Journals (Sweden)

    Cianciolo George

    2008-03-01

    Full Text Available Abstract Background LMP-420 is a boronic acid-containing purine nucleoside analogue that transcriptionally inhibits TNF production but is non-cytotoxic to TNF-producing cells. Methods This study investigated the efficacy of LMP-420 as an anti-inflammatory agent in acute and chronic colitis induced by oral administration of dextran sulfate sodium (DSS to mice and in chronic colitis following piroxicam administration to IL-10-deficient mice. The severity of colon inflammation was assessed histologically. TNF levels were measured by enzyme immunoassay. Results Administration of DSS for 7 days resulted in severe acute colitis that was associated with a marked increase in stool and colon tissue TNF levels. Initiation of therapy with intraperitoneal (i.p. LMP-420 on day 4 of DSS exposure decreased colonic TNF to near normal levels on day 7. However, neither i.p. nor oral treatment with LMP-420 affected the development or severity of acute DSS colitis. Initiation of LMP-420 therapy after 3 cycles of DSS administration to establish chronic colitis also had no effect on the severity of chronic colitis. Analysis of colonic TNF combined with longitudinal analysis of TNF and TNF receptor (TNF-RII levels in stool during the development of chronic DSS colitis demonstrated that the initially elevated colonic TNF levels returned to normal despite intense on-going inflammation in mice with chronic colitis. RAG-2-/- mice deficient in T and B cells also developed severe ongoing colitis in response to 3 cycles of DSS, but showed marked differences vs. wild type mice in stool TNF and TNF-RII in response to DSS exposure. Systemic and oral LMP-420 treatment for 16 days decreased colonic TNF levels in IL-10-deficient mice with chronic colitis, with a trend to decreased histologic inflammation for oral LMP-420. Conclusion These studies demonstrate that short-term treatment with a transcriptional inhibitor of TNF production can decrease systemic and local colonic levels

  11. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

    Directory of Open Access Journals (Sweden)

    Emily L Lowe

    2010-09-01

    Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

  12. Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats.

    Science.gov (United States)

    Boussenna, Ahlem; Goncalves-Mendes, Nicolas; Joubert-Zakeyh, Juliette; Pereira, Bruno; Fraisse, Didier; Vasson, Marie-Paule; Texier, Odile; Felgines, Catherine

    2015-12-01

    Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4% w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.

  13. Diet in the Aetiology of Ulcerative Colitis: A European Prospective Cohort Study

    DEFF Research Database (Denmark)

    Hart, Andrew R; Luben, Robert; Olsen, Anja

    2008-01-01

    Background/Aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake...... was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. Results: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected......, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). Conclusions: No associations between ulcerative colitis and diet were detected, apart from...

  14. Probiotics and prebiotics in ulcerative colitis.

    Science.gov (United States)

    Derikx, Lauranne A A P; Dieleman, Levinus A; Hoentjen, Frank

    2016-02-01

    The intestinal microbiota is one of the key players in the etiology of ulcerative colitis. Manipulation of this microflora with probiotics and prebiotics is an attractive strategy in the management of ulcerative colitis. Several intervention studies for both the induction and maintenance of remission in ulcerative colitis patients have been performed. Most of these studies evaluated VSL#3 or E. Coli Nissle 1917 and in general there is evidence for efficacy of these agents for induction and maintenance of remission. However, studies are frequently underpowered, lack a control group, and are very heterogeneous investigating different probiotic strains in different study populations. The absence of well-powered robust randomized placebo-controlled trials impedes the widespread use of probiotics and prebiotics in ulcerative colitis. However, given the promising results that are currently available, probiotics and prebiotics may find their way to the treatment algorithm for ulcerative colitis in the near future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect.

    Science.gov (United States)

    Aldini, Rita; Budriesi, Roberta; Roda, Giulia; Micucci, Matteo; Ioan, Pierfranco; D'Errico-Grigioni, Antonia; Sartini, Alessandro; Guidetti, Elena; Marocchi, Margherita; Cevenini, Monica; Rosini, Francesca; Montagnani, Marco; Chiarini, Alberto; Mazzella, Giuseppe

    2012-01-01

    Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

  16. Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

    Science.gov (United States)

    Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

    2015-12-14

    To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment

  17. Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

    OpenAIRE

    Albrecht Neesse; Patrick Michl; Steffen Kunsch; Volker Ellenrieder; Thomas M. Gress; Martin Steinkamp

    2007-01-01

    Pyoderma gangrenosum (PG) is an immune-mediated inflammatory skin condition representing one of the most distinct extraintestinal manifestations of inflammatory bowel disease (IBD). PG occurs independently from intestinal disease activity in about 1–2% of patients suffering from ulcerative colitis or Crohn's disease and is characterized by chronic deep skin ulcers whose exact pathogenesis is still unknown. So far, patients with ulcerative colitis have only been reported to develop PG during t...

  18. Eosinophilic colitis in infants.

    Science.gov (United States)

    Lozinsky, Adriana Chebar; Morais, Mauro Batista de

    2014-01-01

    To review the literature for clinical data on infants with allergic or eosinophilic colitis. MEDLINE search of all indexes was performed using the words "colitis or proctocolitis and eosinophilic" or "colitis or proctocolitis and allergic" between 1966 and February of 2013. All articles that described patients' characteristics were selected. A total of 770 articles were identified, of which 32 met the inclusion criteria. The 32 articles included a total of 314 infants. According to the available information, 61.6% of infants were male and 78.6% were younger than 6 months. Of the 314 patients, 49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and 6.8% received soy protein. Diarrheal stools were described in 28.3% of patients. Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy showed infiltration by eosinophils (between 5 and 25 per high-power field) in 89.3% (236/264) of patients. Most patients showed improvement with the removal of the protein in cow's milk from their diet or the mother's diet. Allergy challenge tests with cow's milk protein were cited by 12 of the 32 articles (66 patients). Eosinophilic colitis occurs predominantly in the first six months of life and in males. Allergy to cow's milk was considered the main cause of eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating mother or from the infant's diet is generally an effective therapeutic measure. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Infliximab-associated alveolitis after treatment for severe left-sided ulcerative colitis.

    LENUS (Irish Health Repository)

    Veerappan, Sundaram G

    2012-02-01

    Here we describe a patient with ulcerative colitis who developed alveolitis after infliximab therapy. With earlier case reports of development of alveolitis in rheumatoid arthritis patients after infliximab infusion, the temporal relationship between the infliximab therapy and the development of alveolitis in this case, raises the possibility that the two might be causally related. With an increasing trend towards treating moderate to severely active ulcerative colitis patients with infliximab as a rescue therapy, clinicians should be aware of this potentially serious complication.

  20. Management of ulcerative colitis: a clinical update

    Directory of Open Access Journals (Sweden)

    Fabio Vieira Teixeira

    2015-10-01

    Full Text Available The objective of this study was to evaluate the consensus of expert societies and published guidelines on the management of ulcerative colitis, and to compare with the experience of the authors, in order to standardize procedures that would help the reasoning and decision-making process of the physician. A search was performed in scientific literature, specifically in electronic databases: Medline/Pubmed, SciELO, EMBASE and Cochrane, and the following descriptors were used: ulcerative colitis, acute colitis, clinical treatment, surgery and randomized trial. It can be concluded that the goals of therapy in ulcerative colitis are clinical and endoscopic remission, deep, sustained remission without corticosteroids, prevention of hospitalizations and surgeries, and improved quality of life. The surgical indications are reserved for selected cases, ranging from medical intractability, complications (severe refractory acute colitis, toxic megacolon, perforation and hemorrhage and malignancy. Information in this review article must be submitted to evaluation and criticism of the specialist responsible for the conduct to be followed, in the face of his/her reality and the clinical status of each patient.The degree of recommendation and strength of evidence were based using the GRADE system (The Grades of Recommendation, Assessment, Development, and Evaluation described below:1. A: Experimental or observational studies of higher consistency.2. B: Experimental or observational studies of lower consistency.3. C: Case reports (non-controlled studies.4. D: Opinion without critical evaluation, based on consensus, physiological studies or animal models. Resumo: O objetivo deste trabalho foi avaliar os consensos de sociedades de especialistas e guidelines publicados sobre o manejo da retocolite ulcerativa, e confrontar com a experiência dos autores, a fim de padronizar condutas que auxiliem o raciocínio e a tomada de decisão do médico. Foi realizada busca

  1. Collagenous colitis: histopathology and clinical course.

    Science.gov (United States)

    Goff, J S; Barnett, J L; Pelke, T; Appelman, H D

    1997-01-01

    Collagenous colitis is a chronic diarrheal disease characterized by a normal or near-normal mucosa endoscopically and microscopic inflammation in the lamina propria, surface epithelial injury and a thick subepithelial collagen layer. The symptoms of collagenous colitis vary in duration and intensity, and long periods of remission have been described, but long-term follow-up data are limited. Our goal was to determine the natural clinical history of collagenous colitis and to determine whether there was a relationship between histopathologic changes and course of disease. Cases were identified at the University of Michigan Hospitals using surgical pathology records before 1992. All charts, including medical records from other hospitals, were reviewed, and a telephone interview was conducted with each locatable patient (pt). Biopsy specimens were reviewed by two pathologists for degree of collagen layer thickness, epithelial damage, and inflammation. There were 31 patients (26 F, 5 M) with a mean age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22 (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27 of 31 patients (3 could not be located, 1 died). Two definable groups of patients were identified: (1) those with either spontaneous or treatment-related symptom resolution (63%), and (2) those with ongoing or intermittent symptoms requiring at least intermittent therapy (37%). There was no significant difference between the two groups with regard to sex, age, associated diseases, and use of medications. Patients with symptom resolution (mean duration 3.1 yr) had been treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing symptoms experienced a wide range of

  2. Temporal comorbidity of mental disorder and ulcerative colitis.

    Science.gov (United States)

    Cawthorpe, David; Davidson, Marta

    2015-01-01

    Ulcerative colitis is an inflammatory bowel disease that rarely exists in isolation in affected patients. We examined the association of ulcerative colitis and International Classification of Diseases mental disorder, as well as the temporal comorbidity of three broad International Classification of Diseases groupings of mental disorders in patients with ulcerative colitis to determine if mental disorder is more likely to occur before or after ulcerative colitis. We used physician diagnoses from the regional health zone of Calgary, Alberta, for patient visits from fiscal years 1994 to 2009 for treatment of any presenting concern in that Calgary health zone (763,449 patients) to identify 5113 patients age younger than 1 year to age 92 years (2120 males, average age = 47 years; 2993 females, average age = 48 years) with a diagnosis of ulcerative colitis. The 16-year cumulative prevalence of ulcerative colitis was 0.0058%, or 58 cases per 10,000 persons (95% confidence interval = 56-60 per 10,000). Although the cumulative prevalence of mental disorder in the overall sample was 5390 per 10,000 (53.9%), we found that 4192 patients with ulcerative colitis (82%) also had a diagnosis of a mental disorder. By annual rate of ulcerative colitis, patients with mental disorder had a significantly higher annual prevalence. The mental disorder grouping neuroses/depressive disorders was most likely to arise before ulcerative colitis (odds ratio = 1.87 for males; 2.24 for females). A temporal association was observed between specific groups of International Classification of Diseases mental disorder and ulcerative colitis, indicating a possible etiologic relationship between the disorders or their treatments, or both.

  3. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  4. Histology of microscopic colitis-review with a practical approach for pathologists.

    Science.gov (United States)

    Langner, Cord; Aust, Daniela; Ensari, Arzu; Villanacci, Vincenzo; Becheanu, Gabriel; Miehlke, Stephan; Geboes, Karel; Münch, Andreas

    2015-04-01

    Microscopic colitis has emerged as a major cause of chronic watery non-bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathological phenotypes and no significant endoscopic abnormalities. Lymphocytic colitis is defined by an increased number of surface intraepithelial lymphocytes, and collagenous colitis by a thickened collagen band underneath the surface epithelium. There is increased inflammation in the lamina propria, but only little or no crypt architectural distortion. Incomplete and variant forms showing less characteristic features have been reported under different names. The differential diagnosis mainly includes resolving infectious colitis and changes related to the intake of drugs such as non-steroidal anti-inflammatory drugs. Substantial clinical and histological overlap between lymphocytic and collagenous colitis has been described, raising the suspicion that the conditions are two histological manifestations of the same entity, possibly representing different manifestations during the disease course or different stages of disease development. In this review, we provide a practical approach for pathologists, with a focus on diagnostic criteria and differential diagnosis, and discuss recent insights into the pathogenesis of disease and the relationship with classic chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative colitis. © 2014 John Wiley & Sons Ltd.

  5. Peculiarities of the course of ulcerative colitis in children at the present stage

    Directory of Open Access Journals (Sweden)

    M.F. Denisova

    2017-03-01

    Full Text Available Background. As to severity of the course, the incidence of complications and mortality rate, ulcerative colitis hold a position within the top of the gastrointestinal system diseases in children. Goal of research — to study peculiarities of the course of ulcerative colitis at the present stage. Materials and methods. The retrospective analysis was conducted of 184 clinical records of the children, who were on examination and treatment at the Department of the diseases of gastrointestinal system of the State Institution “Institute of Pediatrics, Obstetrics and Gynecology of the National Academy of Medical Sciences of Ukraine” between 2004 and 2014. Results and discussion. Ulcerative colitis is common in the children of all ages, among which the preschool children and teenagers are at greater risk than others. The risk factors include both the antenatal and the postnatal ones: gestational toxicosis and miscarriage threat, weight deficit at birth, artificial feeding, intestinal infections. Ulcerative colitis is characterized by chronic relapse, slow progression of the disease, and the typical clinical symptoms are: diarrhea, hemorrhagic colitis, abdominal pain syndrome, toxic syndrome, late physical development. In terms of localization, the inflammation process most often affects the entire large bowel (59.6 %, left-sided colitis (28.5 %, and proctosigmoiditis (accounts for 11.9 % are less common. The informative criteria of ulcerative colitis activity are the Pediatric Ulcerative Colitis Activity Index (PUCAI, fecal calprotectin level, a number of complete blood count values (hemoglobin, leucocytes, platelets, erythrocyte sedimentation rate and biochemical studies (C-reactive protein, alpha-2 globulins. The modern combined baseline therapy is efficient in 22 % of patients suffering from total colitis, in 42–58 % — from left-sided colitis according to the follow-up study results. Monotherapy with 5-aminosalicylic acid medications was

  6. CT evaluation of infectious colitis

    International Nuclear Information System (INIS)

    Horiki, Noriyuki; Maruyama, Masataka; Fujita, Yoshiyuki; Suzuki, Yuko; Tanaka, Tsuyoshi; Imoto, Ichiro; Adachi, Yukihiko

    2002-01-01

    Computed tomography (CT) is useful for evaluating the diagnosis of gastrointestinal disease, such as infectious colitis, in patients with severe pain and bloody diarrhea. During the 7 years between November 1993 and October 2000, 34 patients with infectious colitis (18 male, 16 female; mean age 42±19 yrs), received emergency CT and colonoscopy because of severe abdominal pain and dysentery. The following organisms were isolated: pathogenic Escherichia coli (12), 6 of which were O157: H7 (O-157), Salmonella species (11), Campylobacter species (5), Vibrio parahaemolyticus (3), Yersinia enterocolotica (2) and Shigella species (1). Thickening of the intestinal wall greater than 10 mm was seen in the ascending colon in the 6 cases with E. coli O157, in 5/11 cases with Salmonella, 4/5 with Campylobacter and 1/6 with non-O157 pathogenic E. Coli. marked intestinal wall thickening, greater than 20 mm, was seen in the ascending colon of the 4 of the patients with an O-157 infection. In all patients with O-157 colitis, slight ascites was noted in the pelvic space. In additions, ascites was also seen in 3/13 patients with Salmonella and 1/5 patients with Campylobacter colitis. The CT findings, in the patients with infectious colitis, are non-specific but knowledge and recognition of the findings will help in patient evaluation and proper treatment. (author)

  7. CT evaluation of infectious colitis

    Energy Technology Data Exchange (ETDEWEB)

    Horiki, Noriyuki; Maruyama, Masataka; Fujita, Yoshiyuki; Suzuki, Yuko [Saint Luke' s International Hospital, Tokyo (Japan); Tanaka, Tsuyoshi; Imoto, Ichiro [National Mie Chuo Hospital, Hisai (Japan); Adachi, Yukihiko [Mie Univ., Tsu (Japan). School of Medicine

    2002-08-01

    Computed tomography (CT) is useful for evaluating the diagnosis of gastrointestinal disease, such as infectious colitis, in patients with severe pain and bloody diarrhea. During the 7 years between November 1993 and October 2000, 34 patients with infectious colitis (18 male, 16 female; mean age 42{+-}19 yrs), received emergency CT and colonoscopy because of severe abdominal pain and dysentery. The following organisms were isolated: pathogenic Escherichia coli (12), 6 of which were O157: H7 (O-157), Salmonella species (11), Campylobacter species (5), Vibrio parahaemolyticus (3), Yersinia enterocolotica (2) and Shigella species (1). Thickening of the intestinal wall greater than 10 mm was seen in the ascending colon in the 6 cases with E. coli O157, in 5/11 cases with Salmonella, 4/5 with Campylobacter and 1/6 with non-O157 pathogenic E. Coli. marked intestinal wall thickening, greater than 20 mm, was seen in the ascending colon of the 4 of the patients with an O-157 infection. In all patients with O-157 colitis, slight ascites was noted in the pelvic space. In additions, ascites was also seen in 3/13 patients with Salmonella and 1/5 patients with Campylobacter colitis. The CT findings, in the patients with infectious colitis, are non-specific but knowledge and recognition of the findings will help in patient evaluation and proper treatment. (author)

  8. Interobserver variability and feasibility of polymerase chain reaction-based assay in distinguishing ischemic colitis from Clostridium difficile colitis in endoscopic mucosal biopsies.

    Science.gov (United States)

    Wiland, Homer O; Procop, Gary W; Goldblum, John R; Tuohy, Marion; Rybicki, Lisa; Patil, Deepa T

    2013-06-01

    Polymerase chain reaction (PCR)-based assays using stool samples are currently the most effective method of detecting Clostridium difficile. This study examines the feasibility of this assay using mucosal biopsy samples and evaluates the interobserver reproducibility in diagnosing and distinguishing ischemic colitis from C difficile colitis. Thirty-eight biopsy specimens were reviewed and classified by 3 observers into C difficile and ischemic colitis. The findings were correlated with clinical data. PCR was performed on 34 cases using BD GeneOhm C difficile assay. The histologic interobserver agreement was excellent (κ= 0.86) and the agreement between histologic and clinical diagnosis was good (κ = 0.84). All 19 ischemic colitis cases tested negative (100% specificity) and 3 of 15 cases of C difficile colitis tested positive (20% sensitivity). C difficile colitis can be reliably distinguished from ischemic colitis using histologic criteria. The C difficile PCR test on endoscopic biopsy specimens has excellent specificity but limited sensitivity.

  9. Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

    Directory of Open Access Journals (Sweden)

    Albrecht Neesse

    2007-10-01

    Full Text Available Pyoderma gangrenosum (PG is an immune-mediated inflammatory skin condition representing one of the most distinct extraintestinal manifestations of inflammatory bowel disease (IBD. PG occurs independently from intestinal disease activity in about 1–2% of patients suffering from ulcerative colitis or Crohn’s disease and is characterized by chronic deep skin ulcers whose exact pathogenesis is still unknown. So far, patients with ulcerative colitis have only been reported to develop PG during the course of IBD but not at the initial manifestation of bowel symptoms. This is the first report demonstrating the simultaneous onset of ulcerative colitis and severe multifocal PG. In addition, we provide first evidence that infliximab may have a particularly powerful effect in early disseminated PG compared to late-onset PG, advocating an early application of this drug.

  10. Segmental Colitis Complicating Diverticular Disease

    Directory of Open Access Journals (Sweden)

    Guido Ma Van Rosendaal

    1996-01-01

    Full Text Available Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients with underlying diverticulosis are presented. Segmental resection has permitted close review of the histopathology in this syndrome which demonstrates considerable similarity to changes seen in idiopathic ulcerative colitis. The reported experience with this syndrome and its clinical features are reviewed.

  11. Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Aya Nakaya

    2017-12-01

    Full Text Available A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

  12. Allergic colitis: a mimic of Hirschsprung disease

    International Nuclear Information System (INIS)

    Bloom, D.A.; Buonomo, C.; Fishman, S.J.; Furuta, G.; Nurko, S.

    1999-01-01

    Background. Allergy to cow milk protein is a common cause of gastrointestinal symptoms in infancy. Milk allergy is usually a clinical diagnosis, and thus there have been few reports of the radiographic findings. Objective. To describe the barium enema findings of allergic colitis and differentiate them from Hirschsprung disease. Materials and methods. Four infants (age range 7 days-5 weeks) with constipation underwent barium enema to exclude Hirschsprung disease. Radiographic findings were correlated with the pathologic specimens from suction rectal biopsy. Results. All enemas revealed irregular narrowing of the rectum and a transition zone. Rectal biopsies in each case demonstrated ganglion cells and evidence of an allergic colitis, with inflammatory infiltrates in the lamina propria. A diagnosis of milk allergy colitis was made and symptoms resolved after removal of milk from the diet. Conclusions. Milk allergy is common in infancy. The rectum is a primary target organ, with allergic colitis often diagnosed on clinical grounds alone. However, a child with allergic colitis may be referred to radiology for barium enema, especially if constipation is present. The radiologist should be aware of the unique imaging findings of allergic colitis, so as to avoid confusion with Hirschsprung disease and perhaps an unnecessary rectal biopsy. (orig.)

  13. Probiotics and prebiotics in ulcerative colitis

    NARCIS (Netherlands)

    Derikx, L.A.A.P.; Dieleman, L.A.; Hoentjen, F.

    2016-01-01

    The intestinal microbiota is one of the key players in the etiology of ulcerative colitis. Manipulation of this microflora with probiotics and prebiotics is an attractive strategy in the management of ulcerative colitis. Several intervention studies for both the induction and maintenance of

  14. Unusual complication of toxic megacolon in typhoid colitis.

    Science.gov (United States)

    Arun Babu, Thirunavukkarasu; Ananthakrishnan, Shanthi; Jayakumar, P; Kullu, Poonam

    2014-05-01

    Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.

  15. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis: Case report and review of the literature.

    Science.gov (United States)

    Phadke, Varun K; Friedman-Moraco, Rachel J; Quigley, Brian C; Farris, Alton B; Norvell, J P

    2016-10-01

    Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease.

  16. Spontaneous long-range calcium waves in developing butterfly wings.

    Science.gov (United States)

    Ohno, Yoshikazu; Otaki, Joji M

    2015-03-25

    Butterfly wing color patterns emerge as the result of a regular arrangement of scales produced by epithelial scale cells at the pupal stage. These color patterns and scale arrangements are coordinated throughout the wing. However, the mechanism by which the development of scale cells is controlled across the entire wing remains elusive. In the present study, we used pupal wings of the blue pansy butterfly, Junonia orithya, which has distinct eyespots, to examine the possible involvement of Ca(2+) waves in wing development. Here, we demonstrate that the developing pupal wing tissue of the blue pansy butterfly displayed spontaneous low-frequency Ca(2+) waves in vivo that propagated slowly over long distances. Some waves appeared to be released from the immediate peripheries of the prospective eyespot and discal spot, though it was often difficult to identify the specific origins of these waves. Physical damage, which is known to induce ectopic eyespots, led to the radiation of Ca(2+) waves from the immediate periphery of the damaged site. Thapsigargin, which is a specific inhibitor of Ca(2+)-ATPases in the endoplasmic reticulum, induced an acute increase in cytoplasmic Ca(2+) levels and halted the spontaneous Ca(2+) waves. Additionally, thapsigargin-treated wings showed incomplete scale development as well as other scale and color pattern abnormalities. We identified a novel form of Ca(2+) waves, spontaneous low-frequency slow waves, which travel over exceptionally long distances. Our results suggest that spontaneous Ca(2+) waves play a critical role in the coordinated development of scale arrangements and possibly in color pattern formation in butterflies.

  17. Desulfovibrio bacterial species are increased in ulcerative colitis.

    LENUS (Irish Health Repository)

    Rowan, Fiachra

    2012-02-01

    BACKGROUND: Debate persists regarding the role of Desulfovibrio subspecies in ulcerative colitis. Combined microscopic and molecular techniques enable this issue to be investigated by allowing precise enumeration of specific bacterial species within the colonic mucous gel. The aim of this study was to combine laser capture microdissection and quantitative polymerase chain reaction to determine Desulfovibrio copy number in crypt-associated mucous gel in health and in acute and chronic ulcerative colitis. METHODS: Colonic mucosal biopsies were harvested from healthy controls (n = 19) and patients with acute (n = 10) or chronic (n = 10) ulcerative colitis. Crypt-associated mucous gel was obtained by laser capture microdissection throughout the colon. Pan-bacterial 16S rRNA and Desulfovibrio copy number\\/mm were obtained by polymerase chain reaction at each locus. Bacterial copy numbers were interrogated for correlation with location and disease activity. Data were evaluated using a combination of ordinary linear methods and linear mixed-effects models to cater for multiple interactions. RESULTS: Desulfovibrio positivity was significantly increased in acute and chronic ulcerative colitis at multiple levels within the colon, and after normalization with total bacterial signal, the relative Desulfovibrio load was increased in acute colitis compared with controls. Desulfovibrio counts did not significantly correlate with age, disease duration, or disease activity but interlevel correlations were found in adjacent colonic segments in the healthy control and chronic ulcerative colitis groups. CONCLUSION: The presence of Desulfovibrio subspecies is increased in ulcerative colitis and the data presented suggest that these bacteria represent an increased percentage of the colonic microbiome in acute ulcerative colitis.

  18. Necrotizing colitis associated with carcinoma of the colon

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Lim, Jae Hoon; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Necrotizing colitis associated with carcinoma of the colon, known also as obstructive colitis, is a disorder characterized by anulceration and inflammation of the colon proximal to an obstructive lesion, especially carcinoma of the rectosigmoid colon, and in rare instance, leads to acute gangrene of the colon. The authors analyzed radiologic findings in four cases of necrotizing colitis associated with carcinoma of the colon. Barium enema disclosed mucosal edema, nodular filling defects, irregularity of the colonic contour and typical thumbprinting appearance of involved colon proximal to an obstructing carcinoma of the colon. The mechanism of necrotizing colitis was briefly reviewed

  19. Toxic amebic colitis coexisting with intestinal tuberculosis.

    Science.gov (United States)

    Park, S. C.; Jeon, H. M.; Kim, J. S.; Kim, W. W.; Kim, K. W.; Oh, S. T.; Kim, E. K.; Chang, S. K.; Lee, E. J.

    2000-01-01

    A patient with a fulminant amebic colitis coexisting with intestinal tuberculosis had a sudden onset of crampy abdominal pain, mucoid diarrhea, anorexia, fever and vomiting with signs of positive peritoneal irritation. Fulminant amebic colitis occurring together with intestinal tuberculosis is an uncommon event and may present an interesting patho-etiological relationship. The diagnosis was proven by histopathologic examination of resected specimen. Subtotal colectomy including segmental resection of ileum, about 80 cm in length, followed by exteriorization of both ends, was performed in an emergency basis. Despite all measures, the patient died on the sixth postoperative day. The exact relationship of fulminant amebic colitis and intestinal tuberculosis is speculative but the possibility of a cause and effect relationship exists. Fulminant amebic colitis may readily be confused with other types of inflammatory bowel disease, such as idiopathic ulcerative colitis, Crohn's disease, perforated diverticulitis and appendicitis with perforation. This report draws attention to the resurgence of tuberculosis and amebiasis in Korea, and the need for the high degree of caution required to detect it. PMID:11194200

  20. A case of fulminating amebic colitis associated with toxic megacolon

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Kyung Sik; Lee, Joong Suk; Suh, Soo Jhi [Kyung Hee University Hospital. Seoul (Korea, Republic of)

    1985-12-15

    Amebic colitis was common disease in Korea as well as in the world especially frequent in tropical area such as Africa, India and South America. Clinicopathological forms of this condition were ulcerative rectocolitis (95%), typhloappendicitis (3%), ameboma (1.5%), and fulminating colitis with toxic megacolon (0.5%). The fulminating amebic colitis with toxic megacolon was very rare and dangerous condition which was reported by Wruble on 1966. Toxic megacolon was seen in the cases of ulcerative colitis, Crohn's disease, typhoid fever, cholera, and acute bacillary dysentery. Radiological findings of fulminating amebic colitis with toxic megacolon were megacolon, multiple polypoid filling defects, thumbprinting, and cobble stone appearance, which were resemble with ulcerative colitis. The cause of toxic megacolon was not well known, but it has been speculated that this results from transmural disease with destruction of muscle and the myenteric plexus with resultant loss of muscle tone. Authors experienced a case of fulminating amebic colitis with toxic megacolon which was resemble with ulcerative colitis by radiologically at Kyung Hee University Hospital and reported it with review of the literatures.

  1. A case of fulminating amebic colitis associated with toxic megacolon

    International Nuclear Information System (INIS)

    Cho, Kyung Sik; Lee, Joong Suk; Suh, Soo Jhi

    1985-01-01

    Amebic colitis was common disease in Korea as well as in the world especially frequent in tropical area such as Africa, India and South America. Clinicopathological forms of this condition were ulcerative rectocolitis (95%), typhloappendicitis (3%), ameboma (1.5%), and fulminating colitis with toxic megacolon (0.5%). The fulminating amebic colitis with toxic megacolon was very rare and dangerous condition which was reported by Wruble on 1966. Toxic megacolon was seen in the cases of ulcerative colitis, Crohn's disease, typhoid fever, cholera, and acute bacillary dysentery. Radiological findings of fulminating amebic colitis with toxic megacolon were megacolon, multiple polypoid filling defects, thumbprinting, and cobble stone appearance, which were resemble with ulcerative colitis. The cause of toxic megacolon was not well known, but it has been speculated that this results from transmural disease with destruction of muscle and the myenteric plexus with resultant loss of muscle tone. Authors experienced a case of fulminating amebic colitis with toxic megacolon which was resemble with ulcerative colitis by radiologically at Kyung Hee University Hospital and reported it with review of the literatures.

  2. A case of fulminating amebic colitis associated with toxic megacolon

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Kyung Sik; Lee, Joong Suk; Suh, Soo Jhi [Kyung Hee University Hospital. Seoul (Korea, Republic of)

    1985-12-15

    Amebic colitis was common disease in Korea as well as in the world especially frequent in tropical area such as Africa, India and South America. Clinicopathological forms of this condition were ulcerative rectocolitis (95%), typhloappendicitis (3%), ameboma (1.5%), and fulminating colitis with toxic megacolon (0.5%). The fulminating amebic colitis with toxic megacolon was very rare and dangerous condition which was reported by Wruble on 1966. Toxic megacolon was seen in the cases of ulcerative colitis, Crohn's disease, typhoid fever, cholera, and acute bacillary dysentery. Radiological findings of fulminating amebic colitis with toxic megacolon were megacolon, multiple polypoid filling defects, thumbprinting, and cobble stone appearance, which were resemble with ulcerative colitis. The cause of toxic megacolon was not well known, but it has been speculated that this results from transmural disease with destruction of muscle and the myenteric plexus with resultant loss of muscle tone. Authors experienced a case of fulminating amebic colitis with toxic megacolon which was resemble with ulcerative colitis by radiologically at Kyung Hee University Hospital and reported it with review of the literatures.

  3. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

    Science.gov (United States)

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-09-07

    To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P sleep deprivation.

  4. Usefulness of colonoscopy in ischemic colitis.

    Science.gov (United States)

    Lozano-Maya, M; Ponferrada-Díaz, A; González-Asanza, C; Nogales-Rincón, O; Senent-Sánchez, C; Pérez-de-Ayala, V; Jiménez-Aleixandre, P; Cos-Arregui, E; Menchén-Fernández-Pacheco, P

    2010-07-01

    the ischemic colitis is intestinal the most frequent cause of ischemia. With this work we determine the demographic and clinical characteristics, and the usefulness of the colonoscopy in the patients with ischemic colitis diagnosed in our centre in relation to a change of therapeutic attitude. retrospective study in which were selected 112 patients diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five years. It was analyzed: age, sex, reason for examination, factors of cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic attitude, treatment and outcome. the average age was of 73.64 + or - 12.10 years with an equal incidence in women (50.9%) and the men (49.1%). The associated factors were the HTA (61.1%), tobacco (37.2%) and antecedents of cardiovascular episode (52.2%). The most frequent reason for colonoscopy was rectorrhagia (53.6%) followed of the abdominal pain (30.4%), being urgent the 65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50 increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The serious ischemic colitis (25%) was more frequent in men (64.3%) in urgent indication (85.71%) and attends with high mortality (53.57%). Surgical treatment in the 57.14% was made with a good evolution in the 50%, whereas the patients with mild or moderate ischemic colitis had a better prognosis (favourable evolution in 80.95%) with smaller requirement of the surgical treatment (4.76%), p change of attitude according to the result of the same one. The evidence of a serious colitis supposed an increase of the necessity of surgery and worse prognosis.

  5. IL-9 antibody injection suppresses the inflammation in colitis mice

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Aping [Laboratory of Molecular Cell Biology, Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Cui, Guanglin, E-mail: guanglin.cui@yahoo.com [Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan (China); Faculty of Health, Nord University at Levanger (Norway)

    2015-12-25

    Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

  6. IL-9 antibody injection suppresses the inflammation in colitis mice

    International Nuclear Information System (INIS)

    Yuan, Aping; Yang, Hang; Qi, Haili; Cui, Jing; Hua, Wei; Li, Can; Pang, Zhigang; Zheng, Wei; Cui, Guanglin

    2015-01-01

    Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.

  7. Synaptic model for spontaneous activity in developing networks

    DEFF Research Database (Denmark)

    Lerchner, Alexander; Rinzel, J.

    2005-01-01

    Spontaneous rhythmic activity occurs in many developing neural networks. The activity in these hyperexcitable networks is comprised of recurring "episodes" consisting of "cycles" of high activity that alternate with "silent phases" with little or no activity. We introduce a new model of synaptic...... dynamics that takes into account that only a fraction of the vesicles stored in a synaptic terminal is readily available for release. We show that our model can reproduce spontaneous rhythmic activity with the same general features as observed in experiments, including a positive correlation between...

  8. Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

    Directory of Open Access Journals (Sweden)

    Derek M. Tang

    2014-01-01

    Full Text Available Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

  9. Short-chain inulin-like fructans reduce endotoxin and bacterial translocations and attenuate development of TNBS-induced colitis in rats.

    Science.gov (United States)

    Ito, Hiroyuki; Tanabe, Hiroki; Kawagishi, Hirokazu; Tadashi, Wada; Yasuhiko, Tomono; Sugiyama, Kimio; Kiriyama, Shuhachi; Morita, Tatsuya

    2009-10-01

    Anti-inflammatory effects of short-chain inulin-like fructans (SCF) on trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated in rats, focusing specifically on endotoxin and bacterial translocations. SCF with degrees of polymerization (DP) of 4 and 8 were used. Rats were fed either control diet or diets including 60 g DP4 or DP8 per kilogram for 7 days, and then received intracolonic TNBS and were fed the respective diets for a further 10 days. DP4 and DP8 significantly reduced colonic injuries as assessed by damage score, but the reduction of colonic myeloperoxidase activity was manifest solely with DP8. At 3 days after colitis induction, bacterial translocation to the mesenteric lymph node was significantly lower in the DP4 and DP8 groups, but significant reduction in the portal endotoxin concentration was achieved solely in the DP8 group. Immediately prior to colitis induction, cecal immunoglobulin A and mucin concentrations were higher in the DP4 and DP8 groups, but these changes were abolished at 10 days post colitis induction. The data suggest that SCF exert prophylactic effects against TNBS colitis, presumably as a result of inhibitory effects on endotoxin and bacterial translocations.

  10. Intestinal Giardiasis Disguised as Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Yu Zhen

    2018-01-01

    Full Text Available Parasite-associated colitis is quite rare in clinical practice of Ulcerative Colitis (UC. Here we reported an intestinal giardiasis case that has been diagnosed with UC. Further examination of stool revealed cysts of Giardia. This case completely responded to Albendazole. Giardiasis should be included for the differential diagnosis of UC.

  11. Microscopic colitis and small intestinal bacterial overgrowth--diagnosis behind the irritable bowel syndrome?

    Science.gov (United States)

    Stoicescu, Adriana; Andrei, M; Becheanu, G; Stoicescu, M; Nicolaie, T; Diculescu, M

    2012-01-01

    Some patients previously diagnosed with irritable bowel syndrome (IBS) may develop microscopic colitis or small intestinal bacterial overgrowth (SIBO). To estimate the prevalence of microscopic colitis and SIBO in patients with IBS, to evaluate the symptoms and the efficacy of treatment. We examined patients with IBS admitted in our clinic during a three-year period. We identified patients with microscopic colitis by performing total colonoscopy with multiple biopsies from normal intestinal mucosa and those with SIBO by performing a H2-breath test with glucose. We compared the symptoms and the effectiveness of the treatment. Out of the 132 patients initially diagnosed with IBS 3% (n=4) had microscopic colitis and 43.9% (n=58) had SIBO. Diarrhea was the main symptom in patients with microscopic colitis and SIBO (p=0.041), while abdominal pain, abdominal bloating and flatulence were prominent in IBS patients (p=0.042; p=0.039; p=0.048). Specific treatment with rifaximin in SIBO patients negativated H2-breath test in 70.9% cases. Patients suspected to have irritable bowel syndrome should be evaluated for microscopic colitis and SIBO. The proper diagnosis and the specific treatment may cure some difficult cases of the so called "irritable bowel syndrome".

  12. Ulcerative colitis: pathogenesis, diagnosis, and current treatment.

    Science.gov (United States)

    Griffel, L H; Das, K M

    1996-01-01

    Ulcerative colitis is a chronic inflammatory disease of the colon that affects the rectum and a variable length of contiguous colon. The disease is characterized by rectal bleeding and diarrhea during periods of exacerbation; these symptoms usually abate with treatment. The pathogenic mechanism of ulcerative colitis is believed to be an aberrant immune response in which antibodies are formed against colonic epithelial protein(s). The disease usually presents during the second and third decades of life, with a smaller peak after the age of 60 years. There is a genetic component to ulcerative colitis, with a higher incidence among family members and, particularly, first-degree relatives. Diagnosis depends on several factors, most notably symptoms, demonstration of uniformly inflamed mucosa beginning in the rectum, and exclusion of other causes of colitis, such as infection. There is no medical cure for ulcerative colitis, but medical therapy is effective and can improve or eliminate symptoms in more than 80% of patients. Surgery offers a cure but carries the high price of total colectomy. New surgical methods, such as ileoanal anastomosis, allow for maintenance of bowel continuity and better patient satisfaction.

  13. Diagnosis and management of microscopic colitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Bohr J

    2014-08-01

    Full Text Available Johan Bohr,1,3 Anna Wickbom,1,3 Agnes Hegedus,2 Nils Nyhlin,1,3 Elisabeth Hultgren Hörnquist,3 Curt Tysk1,3 1Division of Gastroenterology, Department of Medicine, 2Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, 3School of Health and Medical Sciences, Örebro University, Örebro, Sweden Abstract: Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of

  14. Interactions Between Diet and the Intestinal Microbiota Alter Intestinal Permeability and Colitis Severity in Mice.

    Science.gov (United States)

    Llewellyn, Sean R; Britton, Graham J; Contijoch, Eduardo J; Vennaro, Olivia H; Mortha, Arthur; Colombel, Jean-Frederic; Grinspan, Ari; Clemente, Jose C; Merad, Miriam; Faith, Jeremiah J

    2018-03-01

    It is not clear how the complex interactions between diet and the intestinal microbiota affect development of mucosal inflammation or inflammatory bowel disease. We investigated interactions between dietary ingredients, nutrients, and the microbiota in specific pathogen-free (SPF) and germ-free (GF) mice given more than 40 unique diets; we quantified individual and synergistic effects of dietary macronutrients and the microbiota on intestinal health and development of colitis. C56BL/6J SPF and GF mice were placed on custom diets containing different concentrations and sources of protein, fat, digestible carbohydrates, and indigestible carbohydrates (fiber). After 1 week, SPF and GF mice were given dextran sulfate sodium (DSS) to induce colitis. Disease severity was determined based on the percent weight change from baseline, and modeled as a function of the concentration of each macronutrient in the diet. In unchallenged mice, we measured intestinal permeability by feeding mice labeled dextran and measuring levels in blood. Feces were collected and microbiota were analyzed by 16S rDNA sequencing. We collected colons from mice and performed transcriptome analyses. Fecal microbiota varied with diet; the concentration of protein and fiber had the strongest effect on colitis development. Among 9 fiber sources tested, psyllium, pectin, and cellulose fiber reduced the severity of colitis in SPF mice, whereas methylcellulose increased severity. Increasing dietary protein increased the density of the fecal microbiota and the severity of colitis in SPF mice, but not in GF mice or mice given antibiotics. Psyllium fiber reduced the severity of colitis through microbiota-dependent and microbiota-independent mechanisms. Combinatorial perturbations to dietary casein protein and psyllium fiber in parallel accounted for most variation in gut microbial density and intestinal permeability in unchallenged mice, as well as the severity of DSS-induced colitis; changes in 1 ingredient

  15. Usefulness of colonoscopy in ischemic colitis Utilidad de la colonoscopia en la colitis isquémica

    Directory of Open Access Journals (Sweden)

    M. Lozano Maya

    2010-08-01

    Full Text Available Background: the ischemic colitis is intestinal the most frequent cause of ischemia. With this work we determine the demographic and clinical characteristics, and the usefulness of the colonoscopy in the patients with ischemic colitis diagnosed in our centre in relation to a change of therapeutic attitude. Method: retrospective study in which were selected 112 patients diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five years. It was analyzed: age, sex, reason for examination, factors of cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic attitude, treatment and outcome. Results: the average age was of 73.64 ± 12.10 years with an equal incidence in women (50.9% and the men (49.1%. The associated factors were the HTA (61.1%, tobacco (37.2% and antecedents of cardiovascular episode (52.2%. The most frequent reason for colonoscopy was rectorrhagia (53.6% followed of the abdominal pain (30.4%, being urgent the 65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50 increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The serious ischemic colitis (25% was more frequent in men (64.3% in urgent indication (85.71% and attends with high mortality (53.57%. Surgical treatment in the 57.14% was made with a good evolution in the 50%, whereas the patients with mild or moderate ischemic colitis had a better prognosis (favourable evolution in 80.95% with smaller requirement of the surgical treatment (4.76%, p Introducción: la colitis isquémica es la causa más frecuente de isquemia intestinal. Realizamos un estudio con el objetivo de analizar las características demográficas, clínicas y la utilidad de la colonoscopia en los pacientes diagnosticados de colitis isquémica en nuestro centro en relación a un cambio de actitud terapéutica. Método: estudio retrospectivo en el que se seleccionaron 112 pacientes diagnosticados de colitis isquémica mediante

  16. Detection and diagnosis of colitis on computed tomography using deep convolutional neural networks.

    Science.gov (United States)

    Liu, Jiamin; Wang, David; Lu, Le; Wei, Zhuoshi; Kim, Lauren; Turkbey, Evrim B; Sahiner, Berkman; Petrick, Nicholas A; Summers, Ronald M

    2017-09-01

    Colitis refers to inflammation of the inner lining of the colon that is frequently associated with infection and allergic reactions. In this paper, we propose deep convolutional neural networks methods for lesion-level colitis detection and a support vector machine (SVM) classifier for patient-level colitis diagnosis on routine abdominal CT scans. The recently developed Faster Region-based Convolutional Neural Network (Faster RCNN) is utilized for lesion-level colitis detection. For each 2D slice, rectangular region proposals are generated by region proposal networks (RPN). Then, each region proposal is jointly classified and refined by a softmax classifier and bounding-box regressor. Two convolutional neural networks, eight layers of ZF net and 16 layers of VGG net are compared for colitis detection. Finally, for each patient, the detections on all 2D slices are collected and a SVM classifier is applied to develop a patient-level diagnosis. We trained and evaluated our method with 80 colitis patients and 80 normal cases using 4 × 4-fold cross validation. For lesion-level colitis detection, with ZF net, the mean of average precisions (mAP) were 48.7% and 50.9% for RCNN and Faster RCNN, respectively. The detection system achieved sensitivities of 51.4% and 54.0% at two false positives per patient for RCNN and Faster RCNN, respectively. With VGG net, Faster RCNN increased the mAP to 56.9% and increased the sensitivity to 58.4% at two false positive per patient. For patient-level colitis diagnosis, with ZF net, the average areas under the ROC curve (AUC) were 0.978 ± 0.009 and 0.984 ± 0.008 for RCNN and Faster RCNN method, respectively. The difference was not statistically significant with P = 0.18. At the optimal operating point, the RCNN method correctly identified 90.4% (72.3/80) of the colitis patients and 94.0% (75.2/80) of normal cases. The sensitivity improved to 91.6% (73.3/80) and the specificity improved to 95.0% (76.0/80) for the Faster RCNN

  17. Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests.

    OpenAIRE

    Broomé, U; Glaumann, H; Hultcrantz, R

    1990-01-01

    Hepatobiliary disorders are well known complications in patients with ulcerative colitis but it is not possible to predict those patients with ulcerative colitis who will eventually develop liver disease. In this study, liver biopsies from 74 patients with ulcerative colitis have been reevaluated. None of the patients showed clinical or biochemical signs of liver disease at the time of biopsy. Thirty seven (50%) had a completely normal liver biopsy. The others showed minimal portal inflammati...

  18. Collagenous colitis as a possible cause of toxic megacolon.

    LENUS (Irish Health Repository)

    Fitzgerald, S C

    2009-03-01

    Collagenous colitis is a microscopic colitis characterized by normal appearing colonic mucosa on endoscopy. It is regarded as a clinically benign disease which rarely results in serious complications. We report a case of toxic megacolon occurring in a patient with collagenous colitis. This is the first reported case of toxic megacolon occurring in this subset of patients.

  19. Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

    2017-01-01

    Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH-insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance......) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation...

  20. Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

    Science.gov (United States)

    Takamura, Takeyuki; Harama, Daisuke; Fukumoto, Suguru; Nakamura, Yuki; Shimokawa, Naomi; Ishimaru, Kayoko; Ikegami, Shuji; Makino, Seiya; Kitamura, Masanori; Nakao, Atsuhito

    2011-01-01

    Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis. PMID:21321579

  1. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-04-01

    Full Text Available 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.

  2. H. pylori attenuates TNBS-induced colitis via increasing mucosal Th2 cells in mice.

    Science.gov (United States)

    Wu, Yi-Zhong; Tan, Gao; Wu, Fang; Zhi, Fa-Chao

    2017-09-26

    There is an epidemiological inverse relationship between Helicobacter pylori ( H. pylori ) infection and Crohn's disease (CD). However, whether H. pylori plays a protective role against CD remains unclear. Since 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is thought to resemble CD, we investigated whether H. pylori can attenuate TNBS-induced colitis in mice. Here we show that H. pylori can attenuate the severity of TNBS-induced colitis. In addition, H. pylori not only down-regulates Th17 and Th1 cytokine expression, but can up-regulate Th2 cytokine expression and increase the Th2:Th17 ratio of CD4 + T in the colonic mucosa of TNBS-induced colitis. Our results indicate that H. pylori attenuates TNBS-induced colitis mainly through increasing Th2 cells in murine colonic mucosa. Our finding offers a novel view on the role of H. pylori in regulating gastrointestinal immunity, and may open a new avenue for development of therapeutic strategies in CD by making use of asymptomatic H. pylori colonization.

  3. Ethnic Distribution of Microscopic Colitis in the United States.

    Science.gov (United States)

    Turner, Kevin; Genta, Robert M; Sonnenberg, Amnon

    2015-11-01

    A large electronic database of histopathology reports was used to study the ethnic distribution of microscopic colitis in the United States. Miraca Life Sciences is a nation-wide pathology laboratory that receives biopsy specimens submitted by 1500 gastroenterologists distributed throughout the United States. In a case-control study, the prevalence of microscopic colitis in 4 ethnic groups (East Asians, Indians, Hispanics, and Jews) was compared with that of all other ethnic groups (composed of American Caucasians and African Americans), serving as reference group. A total of 11,706 patients with microscopic colitis were included in the analysis. In all ethnic groups alike, microscopic colitis was more common in women than men (78% versus 22%, odds ratio = 3.40, 95% confidence interval = 3.26-3.55). In all ethnic groups, the prevalence of microscopic colitis showed a continuous age-dependent rise. Hispanic patients with microscopic colitis were on average younger than the reference group (59.4 ± 16.2 years versus 64.2 ± 13.8 years, P variations of its occurrence among different ethnic groups. Such variations could point at differences in the exposure to environmental risk factors.

  4. How Common-and How Serious- Is Clostridium difficile Colitis After Geriatric Hip Fracture? Findings from the NSQIP Dataset.

    Science.gov (United States)

    Bovonratwet, Patawut; Bohl, Daniel D; Russo, Glenn S; Ondeck, Nathaniel T; Nam, Denis; Della Valle, Craig J; Grauer, Jonathan N

    2018-03-01

    Patients with geriatric hip fractures may be at increased risk for postoperative Clostridium difficile colitis, which can cause severe morbidity and can influence hospital quality metrics. However, to our knowledge, no large database study has calculated the incidence of, factors associated with, and effect of C. difficile colitis on geriatric patients undergoing hip fracture surgery. To use a large national database with in-hospital and postdischarge data (National Surgical Quality Improvement Program [NSQIP®]) to (1) determine the incidence and timing of C. difficile colitis in geriatric patients who underwent surgery for hip fracture, (2) identify preoperative and postoperative factors associated with the development of C. difficile colitis in these patients, and (3) test for an association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality. This is a retrospective study. Patients who were 65 years or older who underwent hip fracture surgery were identified in the 2015 NSQIP database. The primary outcome was a diagnosis of C. difficile colitis during the 30-day postoperative period. Preoperative and procedural factors were tested for association with the development of C. difficile colitis through a backward stepwise multivariate model. Perioperative antibiotic type and duration were not included in the model, as this information was not recorded in the NSQIP. The association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality were tested through multivariate regressions, which adjusted for preoperative and procedural characteristics such as age, comorbidities, and surgical procedure. A total of 6928 patients who were 65 years or older and underwent hip fracture surgery were identified. The incidence of postoperative C. difficile colitis was 1.05% (95% CI, 0.81%-1.29%; 73 of 6928 patients). Of patients who had C. difficile colitis develop, 64% (47 of 73

  5. Acute nonsteroidal anti-inflammatory drug-induced colitis

    Directory of Open Access Journals (Sweden)

    Massimo Tonolini

    2013-01-01

    Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

  6. Emergency colectomy for fulminant Clostridium difficile colitis: Striking the right balance.

    Science.gov (United States)

    Osman, Khalid A; Ahmed, Mohamed H; Hamad, Mahir A; Mathur, Dilip

    2011-10-01

    The number of reported cases of Clostridium difficile (CD) infections has increased markedly worldwide. CD causes a spectrum of clinical syndromes, ranging from mild diarrhea to a very severe illness in the form of pseudomembranous colitis (PMC), toxic megacolon, leading to colonic perforation, peritonitis, and even death. In today's practice, toxic megacolon is more often caused by pseudomembranous colitis than ulcerative colitis. There is urgent need to establish clear guidelines about how and when to refer patients with fulminant CD colitis to surgeons. Furthermore, there is no strict protocol for the timing of surgical intervention. The aim of this review is to review the available evidence about the criteria for referral to surgeons and timing for surgery. Medline search was carried out for articles published on fulminant CD colitis with emergency colectomy from 1966 to 2010. There were no prospective randomized trails. All retrospective cohort and case control studies were included. We excluded case reports, letters, and studies with less than five patients. Our search showed that patients with confirmed or suspected CD who failed to respond to maximum medical therapy and develop three of the following should be referral for surgical assessment: abdominal pain, abdominal distension, localized tenderness, pyrexia >38°C, and tachycardia >100 beats per minute. In addition to the above, if the patient is above 65 years old and develops four of the following, they should be considered for an emergency colectomy: WBC >16 × 10⁹/l, lactate >2.2 mmol/l, albumin cases. In the absence of published prospective multicenter trial, we suggest that our criteria may enhance early diagnosis and consideration of early referral for surgery. Ultimately, this may reduce the significant morbidity and mortality associated with FCDC.

  7. Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis.

    Science.gov (United States)

    Ha, Christina; Kornbluth, Asher

    2014-12-01

    The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

  8. Acute Ischaemic Colitis- A Case Report

    Directory of Open Access Journals (Sweden)

    M Basra

    2012-03-01

    Full Text Available Acute ischaemic colitis (AIC is being increasingly recognised as an uncommon cause of abdominal pain associated with fresh bleeding per rectum. It is paramount to maintain a high index of suspicion and adopt appropriate management strategies to avoid complications and inappropriate interventions. In this paper, we describe a case of AIC and review literature pertinent to the management of this condition. Keywords: Ischaemic colitis, acute abdomen, management.

  9. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    Science.gov (United States)

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  10. Sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Ono, Kazuhiko; Nimura, Satoshi; Nishinakagawa, Takuya; Hideshima, Yuko; Enjyoji, Munechika; Nabeshima, Kazuki; Nakashima, Manabu

    2014-03-01

    Sodium 4-phenylbutyrate (PBA) exhibits anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation. In the present study, the effects of PBA on a mouse model of dextran sulfate sodium (DSS)-induced colitis were investigated. The therapeutic efficacy of PBA (150 mg/kg body weight) in DSS-induced colitis was assessed based on the disease activity index (DAI), colon length, the production of inflammatory cytokines and histopathological examination. The results showed an increase in the median survival time in the PBA-treated group compared with that of the untreated DSS control group. DAI scores were lower in the PBA-treated group than in the DSS control group during the 12 days of the experiment. Additionally, PBA treatment inhibited shortening of the colon and the production of the inflammatory cytokines tumor necrosis factor-α, interleukin-1β and IL-6, which were measured in the colonic lavage fluids. Histopathological examination of the DSS control group showed diffused clusters of chronic inflammatory cells infiltrating the lamina propria, partial exfoliation of the surface epithelium and decreased numbers of mature goblet cells. By contrast, in the PBA-treated group the histopathological findings were the same as those of the normal healthy controls. These results suggest that PBA strongly prevents DSS-induced colitis by suppressing the mechanisms involved in its pathogenesis.

  11. Atypical development of spontaneous social cognition in autism spectrum disorders.

    Science.gov (United States)

    Senju, Atsushi

    2013-02-01

    Individuals with autism spectrum disorders (ASD) have profound impairment in the development of social interaction and communication. However, it is also known that some 'high-functioning' individuals with ASD show apparently typical capacity to process social information in a controlled experimental settings, despite their difficulties in daily life. The current paper overviews the spontaneous social cognition, spontaneous processing of social information in the absence of explicit instruction or task demand, in individuals with ASD. Three areas of the researches, false belief attribution, imitation/mimicry, and eye gaze processing, have been reviewed. The literatures suggest that high-functioning individuals with ASD (a) do not spontaneously attribute false belief to others, even though they can easily do so when explicitly instructed, (b) can imitate others' goal-directed actions under explicit instruction and show spontaneous mimicry of others' actions when they attend to the action, but are less likely to show spontaneous mimicry without the task structure to navigate attention to others' action and (c) can process others' gaze direction and shift attention to others' gaze directions, but fail to spontaneously attend to another person's eyes in social and communicative context, and less likely to be prompted to respond in response to perceived eye contact. These results are consistent with the claim that individuals with ASD do not spontaneously attend to socially relevant information, even though they can easily process the same information when their attention is navigated towards it. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

    Directory of Open Access Journals (Sweden)

    Willis Cynthia R

    2012-10-01

    Full Text Available Abstract Background Interleukin-7 (IL-7 acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis (Hb-induced colitis in immune-sufficient Mdr1a−/− mice and in T- and B-cell-deficient Rag2−/− mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb-infected Mdr1a−/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb-infected Mdr1a−/− mice treated with an anti-IL-7R antibody. In Rag2−/− mice where colitis was triggered by Hb-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development

  13. Observer variability in the histopathologic diagnosis of microscopic colitis and subgroups

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Bjørnbak, Camilla; Warnecke, Mads

    2013-01-01

    The diagnosis of microscopic colitis (MC) is based on histologic findings and includes collagenous colitis (CC) and lymphocytic colitis (LC). Incomplete MC (MCi) denotes patients with chronic diarrhea and a normal endoscopy and morphological changes that do not completely meet the histologic crit...

  14. Vedolizumab as induction and maintenance therapy for ulcerative colitis

    DEFF Research Database (Denmark)

    Feagan, Brian G; Rutgeerts, Paul; Sands, Bruce E

    2013-01-01

    Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.......Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis....

  15. Dextran sulfate sodium-induced colitis in piglets

    DEFF Research Database (Denmark)

    Nielsen, Katrine Dalby; Schramm, Andreas; Purup, Stig

    Inflammatory bowel disease (IBD) results from complex interactions between genetic and environmental factors. Although a genetic contribution has been proven, dietary factors have also shown to play a role in the development of IBD. This study aims to investigate the effect of adding red meatto t...... the diet of piglets in a dextran sodium sulfate (DSS)-induced colitis model....

  16. Value of CT in the diagnosis of pseudomembranous colitis

    International Nuclear Information System (INIS)

    Fishman, E.K.; Merine, D.S.; Kuhlman, J.E.; Jones, B.

    1989-01-01

    With the increasing use of Ct as a primary imaging modality in the patient with abdominal distress, it is not surprising the CT may be the initial study to suggest the diagnosis of pseudomembranous colitis. The authors reviewed the CT scans in 16 patients with proved pseudomembranous colitis. In 12 of these cases, the diagnosis was not considered prior to CT. The CT findings included wall thickening (average, 18 mm), definite ulcerations (11 cases), ascites (two cases), and pseudoperforation (three cases). The pseudoperforation is caused by the trapping of contrast material within the large ulcerated mucosal folds and can simulate contrast extravasation. The various CT appearances of pseudomembranous colitis are addressed, as well as the potential difficulty in distinguishing it from other types of colitis

  17. Diagnostic Yield of Microscopic Colitis in Open Access Endoscopy Center.

    Science.gov (United States)

    Ellingson, Derek; Miick, Ronald; Chang, Faye; Hillard, Robert; Choudhary, Abhishek; Ashraf, Imran; Bechtold, Matthew; Diaz-Arias, Alberto

    2011-08-01

    The diagnostic yield in open access endoscopy has been evaluated which generally support the effectiveness and efficiency of open access endoscopy. With a few exceptions, diagnostic yield studies have not been performed in open access endoscopy for more specific conditions. Therefore, we conducted a study to determine the efficiency of open access endoscopy in the detection of microscopic colitis as compared to traditional referral via a gastroenterologist. A retrospective search of the pathology database at the University of Missouri for specimens from a local open access endoscopy center was conducted via SNOMED code using the terms: "microscopic", "lymphocytic", "collagenous", "spirochetosis", "focal active colitis", "melanosis coli" and "histopathologic" in the diagnosis line for the time period between January 1, 2004 and May 25, 2006. Specimens and colonoscopy reports were reviewed by a single pathologist. Of 266 consecutive patients with chronic diarrhea and normal colonoscopies, the number of patients with microscopic disease are as follows: Lymphocytic colitis (n = 12, 4.5%), collagenous colitis (n = 17, 6.4%), focal active colitis (n = 15, 5.6%), and spirochetosis (n = 2, 0.4%). The diagnostic yield of microscopic colitis in this study of an open access endoscopy center does not differ significantly from that seen in major medical centers. In terms of diagnostic yield, open access endoscopy appears to be as effective in diagnosing microscopic colitis.

  18. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  19. Development of the pediatric daily ulcerative colitis signs and symptoms scale (DUCS): qualitative research findings.

    Science.gov (United States)

    Flood, Emuella; Silberg, Debra G; Romero, Beverly; Beusterien, Kathleen; Erder, M Haim; Cuffari, Carmen

    2017-09-25

    The purpose of this study is to develop patient-reported (PRO) and observer-reported (ObsRO) outcome measures of ulcerative colitis (UC) signs/symptoms in children aged 5-17 with mild/moderate UC. The daily ulcerative colitis signs and symptoms scale (DUCS) was developed in two phases. Phase I involved concept elicitation interviews with patients and healthcare providers, review of website posts and item generation. Phase II involved cognitive debriefing and assessment of usability and feasibility of the eDiaries. Participants were recruited from five US clinical sites, a research recruitment agency, and internet advertising. Thematic and content analysis was performed to identify concepts from Phase I. The Phase II cognitive debriefing interviews were analyzed iteratively to identify problems with clarity and relevance of eDiary content. The US Food and Drug Administration (FDA) also reviewed and provided feedback on the eDiaries. Phase I included 32 participants (22 remission; 10 active disease). Phase II included 38 participants (22 remission; 16 active disease). A core set of seven signs and symptoms emerged that were reported by at least 30% of the patients interviewed: abdominal pain, blood in stool, frequent stools, diarrhea, stool urgency, nighttime stools, and tiredness. Participant input influenced changes such as refinement of item wording, revision of graphics, and selection of response scales. Revisions suggested by FDA included simplifying the response scale and adding questions to capture symptoms during sleeping hours. The findings of instrument development suggest that the DUCS PRO and ObsRO eDiaries are content-valid instruments for capturing the daily signs and symptoms of pediatric patients with mild to moderate UC in a clinical trial setting.

  20. The development of spontaneous gender stereotyping in childhood: relations to stereotype knowledge and stereotype flexibility.

    Science.gov (United States)

    Banse, Rainer; Gawronski, Bertram; Rebetez, Christine; Gutt, Hélène; Morton, J Bruce

    2010-03-01

    The development of spontaneous gender stereotyping in children was investigated using the newly developed Action Interference Paradigm (AIP). This task consists of assigning gender-stereotypical toys as quickly as possible to boys and girls in either a stereotype-congruent or a stereotype-incongruent manner. A pilot study with 38 children (mean age 5.1 years) provided evidence for spontaneous gender stereotyping in the AIP, which was reflected in higher latencies for stereotype-incongruent compared with stereotype-congruent toy assignments. The main study, with 66 children (aged 5, 8 and 11 years), compared the development of spontaneous stereotyping with established measures of stereotype flexibility and stereotype knowledge. Stereotype flexibility showed a strong increase from age 5 to 11. In contrast, stereotype knowledge and spontaneous stereotyping remained stable at high levels. The results provide evidence for a dissociation between stereotype flexibility and spontaneous stereotyping, suggesting that spontaneous stereotyping may be more closely related to stereotype knowledge than to stereotype flexibility.

  1. Amyloid Goiter Secondary to Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Bunyamin Aydin

    2016-01-01

    Full Text Available Diffuse amyloid goiter (AG is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn’s disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

  2. Orally administered sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Ono, Kazuhiko; Nimura, Satoshi; Hideshima, Yuko; Nabeshima, Kazuki; Nakashima, Manabu

    2017-12-01

    Sodium 4-phenylbutyrate (PBA) exerts therapeutic effects in a wide range of pathologies. A previous study by the present authors revealed that intraperitoneal administration of PBA suppresses the onset of dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, the effects of orally administered PBA are investigated, as this route of administration is more clinically relevant. The therapeutic efficacy of PBA (10 mg/12 h) in mice with experimental colitis was assessed based on the disease activity index, production of inflammatory cytokines, colon length and histopathological investigations. The results of the present study demonstrated a significantly higher survival rate in the PBA-treated group compared with the PBA-untreated (DSS control) group (P=0.0156). PBA treatment improved pathological indices of experimental colitis (P<0.05). Furthermore, the oral administration of PBA significantly inhibited the DSS-induced shortening of the colon (P<0.05) and overproduction of interleukin (IL)-1β and IL-6 (both P<0.05) as measured in colonic lavage fluids. A marked attenuation of the DSS-induced overproduction of tumor necrosis factor was also observed. For histopathological analysis, a marked decrease in mature goblet cells and increase in enlarged nuclei of the absorptive cells was observed in colon lesions of DSS control mice as compared with normal untreated mice. However, in the PBA-treated mice, no such lesions were observed and the mucosa resembled that of DSS-untreated mice. The results of the present study, combined with those results of a previous study, suggest that oral and intraperitoneal administration of PBA have similar preventative effects on DSS-induced colitis, achieved by suppressing its pathogenesis.

  3. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

    Directory of Open Access Journals (Sweden)

    Valerie A. Allen

    2016-01-01

    Full Text Available Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI. Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  4. Vedolizumab as a Treatment for Crohn’s Disease and Ulcerative Colitis

    Science.gov (United States)

    Ha, Christina

    2014-01-01

    The management of Crohn’s disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn’s disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn’s disease and ulcerative colitis. PMID:27524947

  5. Clinical Presentation of Ulcerative Colitis in Pakistani Adults.

    Science.gov (United States)

    Qureshi, Mustafa; Abbas, Zaigham

    2015-01-01

    The aim of this study was to determine the clinical presentation and severity of ulcerative colitis (UC) in Pakistani adult patients. An observational study. Data were obtained by reviewing the medical records of patients who visited a gastroenterology clinic between 2008 and 2012. There were 54 patients diagnosed as UC. The male to female ratio was 1:1. Mean age at diagnosis of UC was 38.7 ± 11.8 years (median 36.5, range 18-64). The predominant presenting symptoms were mucus diarrhea in 49 (90.7%), gross blood in stools in 42 (77.8%), abdominal pain or cramps in 40 (74.1%) and weight loss in 15 (27.7%). Left-sided colitis was present in 23 (42.6%), pancolitis in 15 (27.8%), extensive colitis in 11 (20.4%), and proctitis in five (9.2%). The severity of UC as judged by the Mayo scoring system showed that 68.5% were suffering from moderate to severe disease while 31.5% had mild disease. The extra-intestinal manifestation were found only in seven patients; arthritis in five patients and anterior uveitis in two patients. The arthritis was unilateral and the sites were knee joint in three patients and sacroiliac joint in two patients. Ulcerative colitis presents in our adult patients may present at any age with no gender preponderance. The disease severity is moderate to severe in the majority of patients and more than half of them have left-sided colitis or pancolitis at the time of presentation. Extraintestinal manifestations were not common. Qureshi M, Abbas Z. Clinical Presentation of Ulcerative Colitis in Pakistani Adults. Euroasian J Hepato-Gastroenterol 2015;5(2):127-130.

  6. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

  7. Mechanism of diarrhea in microscopic colitis.

    Science.gov (United States)

    Protic, Marijana; Jojic, Njegica; Bojic, Daniela; Milutinovic, Svetlana; Necic, Dusanka; Bojic, Bozidar; Svorcan, Petar; Krstic, Miodrag; Popovic, Obren

    2005-09-21

    To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. Seventy-six patients were included: 51 with microscopic colitis (MC) (40 with lymphocytic colitis (LC); 11 with collagenous colitis (CC)); 7 with MC without diarrhea and 18 as a control group (CG). They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium concentration. Fecal fluid sodium concentration was significantly increased in LC 58.11+/-5.38 mmol/L (Pdiarrhea compared to fecal osmotic gap. Seven (13.3%) patients had osmotic diarrhea. Diarrhea in MC mostly belongs to the secretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased Cl/HCO3 exchange rate and increased chloride secretion are coexistent pathways.

  8. Clinical significance of serum sex hormones protein and lipid determination in patients with ulcerative colitis

    International Nuclear Information System (INIS)

    Song Qingzhang; Zhang Min

    2010-01-01

    Objective: To investigate the relationships between changes of serum sex hormones levels and protein-lipid metabolism in patients with ulcerative colitis. Methods: Serum levels of estradiol (E 2 ) pregnenedione (P), prolactin(PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) (with CLIA), sree testos (T, with RIA) and total-protein (TP), albumin (Alb), globulin (G), albumin/globulinratio (A/G) total-cholesterd (TC), high density lipoprotein cholesterols (LDL-C) (with biochemistry were determined in 72 patients) with ulcerative colitis and 72 controls. Results: The serum levels of T, LH, FSH, TP, Alb, A/G, TC, LDL-C in patients with ulcerative colitis were significantly lower than those in controls (P 2 , PRL in patients with ulcerative colitis were significantly higher than those in controls (P 2 were negatively correlated with TP, A/G and TC (P 2 levels in the female sex (P>0.05) as well as between LH, FSH and T levels in the male sex (P>0.05). Conclusion: The abnormal serum levels of sex hormone might contribute to the development of hypoproteinaemia and lowered lipid levels in patients with ulcerative colitis. Treatment with correction of serum sex hormones levels might be beneficial to the patients. (authors)

  9. Confocal laser endomicroscopy in ulcerative colitis

    DEFF Research Database (Denmark)

    Karstensen, John Gásdal; Săftoiu, Adrian; Brynskov, Jørn

    2016-01-01

    BACKGROUND AND AIMS: Confocal laser endomicroscopy enables real-time in vivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study...... was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. METHODS: Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were...

  10. Severe ischemic colitis following olanzapine use: a Case Report

    Directory of Open Access Journals (Sweden)

    Samuel Raimundo Fernandes

    Full Text Available Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

  11. Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ.

    Science.gov (United States)

    Kong, Rui; Luo, Hui; Wang, Nan; Li, Jingjing; Xu, Shizan; Chen, Kan; Feng, Jiao; Wu, Liwei; Li, Sainan; Liu, Tong; Lu, Xiya; Xia, Yujing; Shi, Yanhong; Zhou, Yingqun; He, Weigang; Dai, Qi; Zheng, Yuejuan; Lu, Jie

    2018-01-01

    Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors- γ (PPAR- γ ), Portulaca regulation of PPAR- γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca . Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF- κ B phosphorylation. Furthermore, Portulaca extract restored PPAR- γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR- γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.

  12. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    DEFF Research Database (Denmark)

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...

  13. Inciting and etiologic agents of colitis.

    Science.gov (United States)

    Silva, J; Fekety, R; Werk, C; Ebright, J; Cudmore, M; Batts, D; Syrjamaki, C; Lukens, J

    1984-01-01

    Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

  14. Delayed recurrence of ulcerative colitis manifested by tracheobronchitis, bronchiolitis, and bronchiolectasis

    Directory of Open Access Journals (Sweden)

    Iclal Ocak MD,

    2017-12-01

    Full Text Available Ulcerative colitis can cause inflammation of small and large airways, characterized by mucosal inflammation, tracheobronchial stenosis, bronchiestasis, and bronchiolitis. We present a case of tracheobronchitis and bronchiolitis associated with ulcerative colitis in a 58-year-old nonsmoking man, 17 years after the total colectomy and complete resolution of intestinal findings. Computed tomography demonstrated wall thickening of trachea and left main stem bronchus, and multiple bronchi around the both hilum with mild to moderate stenosis. Fiberoptic bronchial biopsy showed inflammation of the airways, similar to histologic findings of ulcerative colitis within colon. Keywords: Ulcerative colitis, Trachea, Lung

  15. Onset of ulcerative colitis after thyrotoxicosis: a case report and review of the literature.

    Science.gov (United States)

    Laterza, L; Piscaglia, A C; Lecce, S; Gasbarrini, A; Stefanelli, M L

    2016-01-01

    Ulcerative colitis is a chronic disease that could be triggered by acute stressful events, such as gastrointestinal infections or emotional stress. We reported the case of the onset of an ulcerative colitis after a thyrotoxicosis crisis and reviewed the literature about the relationships between thyroid dysfunctions and ulcerative colitis. A 38-year-old woman was diagnosed with ulcerative colitis after her third thyrotoxicosis crisis, two years after the diagnosis of Graves' disease. In this case, thyrotoxicosis acted as a trigger for ulcerative colitis onset. Hyperthyroidism could be a trigger able to elicit ulcerative colitis in susceptible patients.

  16. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS. Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8, colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.

  17. [Allergic colitis in exclusively breast-fed infants].

    Science.gov (United States)

    Sierra Salinas, C; Blasco Alonso, J; Olivares Sánchez, L; Barco Gálvez, A; del Río Mapelli, L

    2006-02-01

    Eosinophilic colitis is induced by antigens present in cow's milk proteins in formula or human milk. In the last few years, an increasing number of cases have been diagnosed in exclusively breast-fed infants. We performed a retrospective study of 13 infants diagnosed with allergic colitis in our unit between January 1997 and January 2004. All the infants had been exclusively breast-fed. In all patients, initial symptoms were digestive (12 with mucus and bloody stools). Onset of symptoms occurred at 0-3 months in 77 %. Laboratory data of the allergic compound were negative. The main locations were the descending and sigmoid colon (75 %). Biopsy demonstrated acute inflammation, with neutrophil infiltration and an increase in eosinophils. In all patients, initial treatment consisted of exclusion of cow's milk proteins from the mother's diet. Ten of the 13 patients showed no improvement, requiring exclusive administration of protein-free hydrolyzate. In 3 infants, breastfeeding was maintained (breastfeeding without cow's milk proteins plus hydrolyzate). Diagnosis of eosinophilic colitis is based on exclusion of other causes of specific colitis and typical endoscopic and ultrastructural findings. Moreover, a satisfactory response to dietary treatment must be demonstrated. This diagnosis should be considered in breast-fed infants with rectal bleeding without involvement of general health status.

  18. Development of a prognostic model for predicting spontaneous singleton preterm birth.

    Science.gov (United States)

    Schaaf, Jelle M; Ravelli, Anita C J; Mol, Ben Willem J; Abu-Hanna, Ameen

    2012-10-01

    To develop and validate a prognostic model for prediction of spontaneous preterm birth. Prospective cohort study using data of the nationwide perinatal registry in The Netherlands. We studied 1,524,058 singleton pregnancies between 1999 and 2007. We developed a multiple logistic regression model to estimate the risk of spontaneous preterm birth based on maternal and pregnancy characteristics. We used bootstrapping techniques to internally validate our model. Discrimination (AUC), accuracy (Brier score) and calibration (calibration graphs and Hosmer-Lemeshow C-statistic) were used to assess the model's predictive performance. Our primary outcome measure was spontaneous preterm birth at model included 13 variables for predicting preterm birth. The predicted probabilities ranged from 0.01 to 0.71 (IQR 0.02-0.04). The model had an area under the receiver operator characteristic curve (AUC) of 0.63 (95% CI 0.63-0.63), the Brier score was 0.04 (95% CI 0.04-0.04) and the Hosmer Lemeshow C-statistic was significant (pvalues of predicted probability. The positive predictive value was 26% (95% CI 20-33%) for the 0.4 probability cut-off point. The model's discrimination was fair and it had modest calibration. Previous preterm birth, drug abuse and vaginal bleeding in the first half of pregnancy were the most important predictors for spontaneous preterm birth. Although not applicable in clinical practice yet, this model is a next step towards early prediction of spontaneous preterm birth that enables caregivers to start preventive therapy in women at higher risk. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina.

    Science.gov (United States)

    Demas, James A; Payne, Hannah; Cline, Hollis T

    2012-04-01

    Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. Copyright © 2011 Wiley Periodicals, Inc.

  20. Ischemic Colitis in an Endurance Runner

    Directory of Open Access Journals (Sweden)

    Chase Grames

    2012-01-01

    Full Text Available A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options.

  1. Consumption of probiotics increases the effect of regulatory T cells in transfer colitis

    DEFF Research Database (Denmark)

    Petersen, Emil Rathsach; Claesson, Mogens Helweg; Schmidt, Esben Gjerløff Wedebye

    2012-01-01

    BACKGROUND: Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function...... of Tregs in vivo. METHODS: Development of colitis after transfer of CD4+CD25- T cells and protection from colitis by Tregs was studied in immunodeficient SCID mice which were simultaneously tube-fed with L. acidophilus NCFM™ or L. salivarius Ls-33 for 5 weeks. RESULTS: Probiotic-fed SCID mice transplanted...... with low numbers of Tregs in addition to the disease-inducing T cells were completely protected from colitis. This was in contrast to the control group, which showed intermediate levels of inflammation. In addition, feeding with probiotics lowered serum levels of inflammatory cytokines in both colitic mice...

  2. The Role of Enteropathogenic E.coli in the Development and Progression of Chronic Non-Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    L.I. Sydorchuk

    2016-04-01

    Full Text Available Objective. The analysis of the literature has shown that in patients with chronic non-ulcerative colitis, there were isolated E.coli that cause dysentery-like, cholera-like diseases and escherichioses. Thus, the aim of our study was to establish the level of persistence of enteropathogenic Escherichia in the colon of patients with chronic non-ulcerative colitis and their importance in the ecological system «macroorganism — microbiota». Material and methods. During 2000–2015, there has been conducted a bacteriological examination of the colon content in patients with chronic non-ulcerative colitis aged 27–41 years (average age 37.74 ± 3.62 years. The resulting cultures were examined in the indicative agglutination tests with OKA polyvalent serum. Positive cultures were tested with polyvalent serum of narrow spectrum ОКВ, ОКС, ОКD and ОКЕ. Results. In patients, in colon cavity of which E.coli O18ac:K77; O26:K60; O55:K59; O128ab:K67 were detected, the disease occurs by nosology of colienteritis. In those patients, in whom O25:K11; O144:K; O124:K72 serotypes have been identified, disease occurred as bacterial dysentery, and O25:K11 and O128:K67 — in chole­ra-like form. Discussion. In 94.50 % of patients, common E.coli were detected, but in 55 (35.03 % of them enteropathogenic Escherichia persist, in 41 (26.11 % — E.coli Hly+, in 37 (23.57 % — E.coli Lac–, in 18 (11.46 % — enterotoxigenic E.coli, in 14 (8.42 % — enteroinvasive, and in 11 (7.01 % — enterohemorragic Escherichia. Conclusions. It was determined that the main serotypes of opportunistic Escherichia, which colonize and persist in the colon cavity of patients with chronic non-ulcerative colitis, were O114:K90; O25:K11; O124:K72; O128:K67; O18ac:K77, the persistence of which affects clinical manifestation from colitis to dysentery-like or cholera-like disease.

  3. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

    LENUS (Irish Health Repository)

    Duffy, M

    2012-02-03

    PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are

  4. Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis.

    Science.gov (United States)

    Kader, H A; Mascarenhas, M R; Piccoli, D A; Stouffer, N O; Baldassano, R N

    1999-01-01

    The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population. The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test. In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients

  5. The economics of adalimumab for ulcerative colitis.

    Science.gov (United States)

    Xie, Feng

    2015-06-01

    Ulcerative colitis is a chronic inflammatory disease, characterized by diffuse mucosal inflammation in the colon. Adalimumab, as a TNF-α blocker, offers a safe and efficacious treatment option for patients with moderate to severe ulcerative colitis and refractory or intolerant to conventional medications; however, its cost-effectiveness profile has not yet been well established. Future economic evaluations should choose appropriate comparators in the context of target-reimbursement decision making and focus on cost-effectiveness over a long time horizon.

  6. Granisetron ameliorates acetic acid-induced colitis in rats.

    Science.gov (United States)

    Fakhfouri, Gohar; Rahimian, Reza; Daneshmand, Ali; Bahremand, Arash; Rasouli, Mohammad Reza; Dehpour, Ahmad Reza; Mehr, Shahram Ejtemaei; Mousavizadeh, Kazem

    2010-04-01

    Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, of which the definite etiology remains ambiguous. Considering the adverse effects and incomplete efficacy of currently administered drugs, it is indispensable to explore new candidates with more desirable therapeutic profiles. 5-HT( 3) receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. This study aims to investigate granisetron, a 5-HT( 3) receptor antagonist, in acetic acid-induced rat colitis and probable involvement of 5-HT(3) receptors. Colitis was rendered by instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT( 3) receptor agonist, or granisetron + mCPBG was given intraperitoneally. Twenty-four hours following colitis induction, animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6). Granisetron or dexamethasone significantly (p granisetron were reversed by concurrent administration of mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid colitis could be mediated by 5-HT(3) receptors.

  7. Lymphocytic Colitis: Pathologic predictors of response to therapy.

    Science.gov (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

    2018-02-13

    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  8. Processed coffee alleviates DSS-induced colitis in mice

    Directory of Open Access Journals (Sweden)

    Bernd L. Fiebich

    2013-05-01

    Full Text Available ABSTRACTBackground: Coffee is one of the most widely consumed beverages in the world and it has been demonstrated that it has important therapeutic activities not only because of its caffeine content but also owing to the presence of other biologically active small molecules such as chlorogenic acid, trigonelline and cyclopentadiones. However, chlorogenic acid is degraded into catechol, pyrogallol and hydroxyhydroquinone, which are thought to induce irritation of the gastric mucosa. To reduce the content of irritant compounds processing methods have been developed prior to roasting the coffee beans.Objectives: The aim of this study was to study the anti-inflammatory and gastro-protective effects of processed coffee (Idee-Kaffee on in LPS-treated human primary monocytes and in a murine model of colon inflammation (IBD model.Results: In this study we have analyzed the effects on inflammatory events in cultured cells and in mice drinking a commercially available processed coffee. The processed coffee inhibited lipopolysaccharide (LPS-induced proinflammatory cytokines such as interleukin (IL-1, tumor necrosis factor (TNF, IL-6 and IL-8, and other inflammatory mediators such as prostaglandin (PGE2 and 8-isoprostane in cultured human primary monocytes. Oral administration of dissolved processed coffee, i.e., in its usual beverage form, improved greatly the adverse macroscopic and histological features of dextran sodium sulfate (DSS-induced colitis in mice in a dose-dependent manner. Processed coffee not only largely prevented DSS-induced colitis but also dramatically suppressed in vivo NF-B and STAT3 activities through inhibition of IB and STAT3 phosphorylation. Furthermore, this solubleFunctional Foods in Health and Disease 2013; 3(5:133-145coffee bean extract reduced the expression of proinflammatory cytokines TNF, IL-11, and IL-6 and the expression of cyclooxygenase (COX-2 in colonic tissues.Conclusions: This work identified

  9. The delay in the development of experimental colitis from isomaltosyloligosaccharides in rats is dependent on the degree of polymerization.

    Directory of Open Access Journals (Sweden)

    Hitoshi Iwaya

    Full Text Available Isomaltosyloligosaccharides (IMO and dextran (Dex are hardly digestible in the small intestine and thus influence the luminal environment and affect the maintenance of health. There is wide variation in the degree of polymerization (DP in Dex and IMO (short-sized IMO, S-IMO; long-sized IMO, L-IMO, and the physiological influence of these compounds may be dependent on their DP.Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3, L-IMO (DP = 8.4, or Dex (DP = 1230 for two weeks. Dextran sulfate sodium (DSS was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa.Our study provided evidence that the physiological effects of α-glucosaccharides on colitis depend on their DP, linkage type, and digestibility.

  10. Extraintestinal manifestations in Crohn's disease and ulcerative colitis

    DEFF Research Database (Denmark)

    Isene, Rune; Bernklev, Tomm; Høie, Ole

    2015-01-01

    BACKGROUND: In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal......, skin, and liver) manifestations: 20.1% versus 10.4% (p colitis compared to proctitis in UC increased the risk of EIM. CONCLUSION: In a European inception cohort, EIMs in IBD...

  11. Dipeptidyl peptidase expression during experimental colitis in mice

    DEFF Research Database (Denmark)

    Yazbeck, Roger; Sulda, Melanie L; Howarth, Gordon S

    2010-01-01

    We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection.......We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection....

  12. Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy

    OpenAIRE

    Vargas,Thiago Jeunon de Sousa; Fialho,Mônica; Santos,Luiza Tavares dos; Rodrigues,Palmira Assis de Jesus Barreto; Vargas,Ana Luisa Bittencourt Sampaio Jeunon; Sousa,Maria Auxiliadora Jeunon

    2013-01-01

    Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The p...

  13. Cancer in colitis: assessment of the individual risk by clinical and histological criteria.

    Science.gov (United States)

    Lennard-Jones, J E; Morson, B C; Ritchie, J K; Shove, D C; Williams, C B

    1977-12-01

    The cancer risk among 229 patients with extensive ulcerative colitis observed during January 1, 1966 to February 29, 1976 is correlated with the length of history and the histological findings in rectal and colonic biopsies. Five patients are known to have developed carcinoma. No carcinoma was observed in 578 patient years of follow-up within 10 years of onset of the colitis, but the risk in the second decade was approximately 1 in 200 patient years and in the third, 1 in 60 patient years. Severe epithelial dysplasia was rare and found in 32 biopsies from 13 patients. No carcinoma has occurred during the period of follow-up in patients without dysplasia. It has not been possible to follow the development of dysplasia in sequential biopsies. Seven patients with consistent severe dysplasia on biopsy have been treated surgically; carcinoma confined to the bowel wall (Dukes' A) was found in 4. A scheme of management for patients with extensive colitis, including regular rectal and colonic biopsies, is proposed. Our results suggest that such a program will isolate a small group of patients who require surgical treatment for established precancerous change or carcinoma with a high likelihood of cure.

  14. Review of chronic ulcerative colitis cases at King Hussein Medical Centre, Jordan.

    Science.gov (United States)

    Ghazzawi, I; Al-Mrayat, Z

    2007-01-01

    Chronic ulcerative colitis is being encountered with increasing frequency in developing countries. In Amman, Jordan, the records of 372 patients with chronic ulcerative colitis diagnosed between 1994 and 2001 were reviewed. Bloody diarrhoea and crampy abdominal pain were the most common presenting symptoms (84% of patients). The mean age at onset was 31.8 years. In two thirds of patients the diagnosis was made more than 1 year after the onset of symptoms. The pattern of the disease differed from that in industrialized countries in the mild course of the disease, the absence of skin manifestations, and the rarity of colorectal cancer in our patients. The mortality rate was 6%.

  15. The role of aminosalicylates in the treatment of ulcerative colitis

    NARCIS (Netherlands)

    van Assche, Gert; Baert, Filip; de Reuck, Marc; de Vos, Martine; de Wit, Olivier; Hoang, Pierre; Louis, Edouard; Mana, Fazia; Pelckmans, Paul; Rutgeerts, Paul; van Gossum, Andre; D'Haens, Geert

    2002-01-01

    Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two

  16. Clostridium difficile Colitis and Neutropenic Fever Associated with Docetaxel Chemotherapy in a Patient with Advanced Extramammary Paget's Disease.

    Science.gov (United States)

    Nonomura, Yumi; Otsuka, Atsushi; Endo, Yuichiro; Fujisawa, Akihiro; Tanioka, Miki; Kabashima, Kenji; Miyachi, Yoshiki

    2012-05-01

    Extramammary Paget's disease is a rare cutaneous malignant neoplasm. Previous studies indicated the efficacy of docetaxel in advanced cases. The common side effects of docetaxel are usually tolerable and seldom life-threatening. We experienced a case of severe pseudomembranous colitis and neutropenic fever that developed just after the first cycle of docetaxel chemotherapy. To the best of our knowledge, there are few reports of pseudomembranous colitis associated with docetaxel administration for skin cancers. The patient showed complete resolution of her symptoms within 2 weeks with an oral metronidazole therapy. During the second and third cycles, the patient received docetaxel safely with lower doses. The present case indicated that pseudomembranous colitis should be included in the differential diagnosis when assessing patients who develop severe diarrhea during systemic chemotherapy with docetaxel.

  17. Spontaneous splenic rupture and Anisakis appendicitis presenting as abdominal pain: a case report

    Directory of Open Access Journals (Sweden)

    Valle Joaquín

    2012-04-01

    Full Text Available Abstract Introduction Anisakidosis, human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis simplex. Acquired by the consumption of raw or undercooked marine fish or squid, anisakidosis occurs where such dietary customs are practiced, including Japan, the coastal regions of Europe and the United States. Rupture of the spleen is a relatively common complication of trauma and many systemic disorders affecting the reticuloendothelial system, including infections and neoplasias. A rare subtype of rupture occurring spontaneously and arising from a normal spleen has been recognized as a distinct clinicopathologic entity. Herein we discuss the case of a woman who presented to our institution with appendicitis secondary to Anisakis and spontaneous spleen rupture. Case presentation We report the case of a 53-year-old Caucasian woman who presented with hemorrhagic shock and abdominal pain and was subsequently found to have spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. She underwent open surgical resection of the splenic rupture and the appendicitis without any significant postoperative complications. Histopathologic examination revealed appendicitis secondary to Anisakis simplex and splenic rupture of undetermined etiology. Conclusions To the best of our knowledge, this report is the first of a woman with the diagnosis of spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. Digestive anisakiasis may present as an acute abdomen. Emergency physicians should know and consider this diagnosis in patients with ileitis or colitis, especially if an antecedent of raw or undercooked fish ingestion is present. Spontaneous rupture of the spleen is an extremely rare event. Increased awareness of this condition will enhance early diagnosis and effective treatment. Further research is required to identify the possible risk factors associated with spontaneous rupture of the spleen.

  18. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

    Science.gov (United States)

    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

  19. Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

    Science.gov (United States)

    Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

    2017-04-01

    Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

  20. Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models

    Directory of Open Access Journals (Sweden)

    Helieh S Oz

    2013-06-01

    Full Text Available Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD. IBD patients commonly use complementary and alternative medications of which the safety, efficacy and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG and sulfasalazine have similar anti-inflammatory properties. Methods: BALB/c mice received Dextran sodium sulfate (DSS to induce colitis (ulcerative colitis model. Exposure of IL-10 deficient mice (BALB/c-background to normal microbiota provoked enterocolitis (mimics Crohn’s disease. Animals were treated with agents incorporated into daily diets. Control animals received sham treatment. Results: DSS-treated animals developed severe bloody diarrhea and colitis (score 0-4, 3.2+0.27. IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine with no major side effects, and further developed less severe colitis/enterocolitis. GrTP, EGCG and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs DSS p<0.05; EGCG, sulfasalazine vs DSS p<0.01. The inflammatory markers TNFα (3-fold, IL-6 (14-fold and serum amyloid A (40-fold increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (2-fold. EGCG additionally reduced leptin levels (p<0.01 while GrTP and sulfasalazine had no effect on leptin levels (p<0.05. Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored

  1. Ulcerative colitis: criteria and methods of prognosis of exacerbation

    Directory of Open Access Journals (Sweden)

    Kashkina E.l.

    2014-09-01

    Full Text Available Objective: research is devoted to the development of criteria and methods for prognosis of the next recurrence of exacerbation of ulcerative colitis (UC after the patient discharged from hospital. Material and Methods: During a period of a year 38 patients with UC were supervised. The criteria used in the prognosis of recurrence included results of the evaluation of quality of life (SF-36 questionnaire, the analysis of the autonomic nervous system (coefficient Hildebrant and Kerdo index and the level of stressful load procedure Holmes-Rage. Results. It has been established that the risk factors for recurrence include low quality of life on the scale of RP, SF and MH SF-36, the coefficient Hildebrant >5.6 units, Kerdo index 314 points. Conclusion: The obtained data have been processed by multivariate mathematical statistics and the obtained analytical expression allows to prognose the time of recurrence of ulcerative colitis.

  2. Stoma-Closure-Induced Fulminant Pseudomembranous Colitis Recovered by Adjunctive Intracolic Vancomycin with Postural Change

    Directory of Open Access Journals (Sweden)

    Yozo Suzuki

    2010-05-01

    Full Text Available A 67-year-old man with a history of low anterior resection and diverting loop transverse colostomy for rectal carcinoma developed fulminant pseudomembranous colitis after stoma closure. Oral administration of vancomycin at 0.5 g every 6 h and colonoscopy with intracolic vancomycin administration was unsuccessful, but continuation of intracolic vancomycin with postural change resulted in dramatic recovery. Postural change may extend the efficacy of intracolic vancomycin, and intracolic vancomycin should be considered as an option between conventional therapy and surgical intervention for pseudomembranous colitis.

  3. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  4. Developments in the treatment of moderate to severe ulcerative colitis: focus on adalimumab

    Directory of Open Access Journals (Sweden)

    Freeman HJ

    2013-11-01

    Full Text Available Hugh J FreemanDepartment of Medicine (Gastroenterology, University of British Columbia, Vancouver, BC, Canada Abstract: In selected patients with moderate to severe active ulcerative colitis who have failed to respond or are poorly responsive to standard pharmacologic forms of treatment with corticosteroids and immunosuppressive agents, therapy with a biological agent may be considered. While infliximab is an established tumor necrosis factor blocker and has a longer history of clinical use, adalimumab is an alternative in the same class and may be employed as an initial biological agent, if indicated for treatment of the disease. Adalimumab may have special appeal to stable users able to self-inject in a home setting rather than a centralized infusion center. Short-term adverse effects have been limited, but long-term adverse events can be serious and remain less well defined. Recently, another agent, subcutaneous golimumab, has also been reported to induce and maintain clinical response and remission in clinical trials, but a large experience has not been accumulated to date in clinical practice. In the future, other biological agents with novel and distinct mechanisms of therapeutic action may become available. Keywords: ulcerative colitis, anti-tumor necrosis factor inhibitors, biological therapy, infliximab, adalimumab

  5. Macrophage expression in acute radiation colitis in rats

    International Nuclear Information System (INIS)

    Tadami, Tokuma; Shichijo, Kazuko; Matsuu, Mutsumi; Niino, Daisuke; Nakayama, Toshiyuki; Nakashima, Masahiro; Sekine, Ichiro

    2003-01-01

    Although radiation therapy is important in the treatment of tumors in pelvic and abdominal region, it may cause radiation injury as a side effect. But there is no effective way of preventing or curing the damages. The mechanism of acute radiation colitis has not been elucidated yet. Our previous reports have revealed that X-ray irradiation induce apoptosis of epithelial stem cells in colon. Then a hypothesis of the radiation colitis can be put forward, DNA damage by irradiation, apoptosis of mucosal epithelial stem cells and degeneration of epithelial gland structure, macrophages phagocyte the debris, being activated and secreting various inflammatory cytokines, infiltration of inflammatory cells. Several recent reports show that macrophages may play an important role in the process of inflammatory bowel diseases such ulcerative colitis or Crohn's disease. We studied radiation colitis using rat animal models. Male Wister rats were irradiated by a single fraction dose of 22.5 Gy X-ray at laparotomy, shielding except for an approximately 2.5 cm length of rectum. Histological changes and macrophage accumulation in the rectum mucosa were evaluated by immunohistochemistry and western blot method with the specimens which were taken on the 1, 2, 3, 4, 5, 6, 7, 10, and 14th day after irradiation. Severe macrophage accumulation in the lamina propria of the rectum was observed on the 5th day. At the same time, severe destruction of mucosal structure and inflammatory cells infiltration were also observed. Based on the potent pro-inflammatory cytokine producing effects of macrophage in rat and the increased expression in inflammatory bowel disease patients, speculate that intervention in the macrophage-cytokine network could form a future target for the treatment of acute radiation colitis. (author)

  6. Glycyrrhetic Acid Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Vivo

    Directory of Open Access Journals (Sweden)

    Yong-Deok Jeon

    2016-04-01

    Full Text Available Glycyrrhizae Radix (GR is a Korean traditional herb medicine that is widely used in clinical health care. Glycyrrhetic acid (GA is an aglycone saponin extracted from GR that has anti-inflammatory, anti-cancer, and anti-viral effects. However, the anti-inflammatory effects of GA in colitis have not been reported. This study investigated the role of GA on ulcerative colitis in a dextran sulfate sodium (DSS-induced mouse colitis model. DSS-treated mice displayed weight loss and shortened colon length compared with control mice. Mice administered GA showed less weight loss and longer colon length than the DSS-treated group. Interleukin (IL-6, IL-1β, and tumor necrosis factor-alpha were decreased by GA treatment. GA treatment also reduced DSS-induced microscopic damage to colon tissue. GA regulates the phosphorylation of transcription factors including nuclear factor-kappa B (NF-κB and IκB alpha, and regulates the expression of cycloxygenase-2 and prostaglandin E2. GA thus showed beneficial effects in a mouse model of colitis, implicating GA might be a useful herb-derived medicine in the treatment of ulcerative colitis.

  7. A case of acute ischemic colitis after endovascular abdominal aortic aneurysm repair

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    Grigorios Voulalas

    2016-01-01

    Full Text Available Colonic ischemia is a recognized complication of either open or endovascular abdominal aortic aneurysm repair. The clinical difficulty in establishing the diagnosis, the severity of this complication and the patient's poor physiological status may lead to a fatal outcome. We presented a case of ischemic colitis in a patient with patent hypogastric arteries that occurred after an endovascular abdominal aortic aneurysm repair as well as a review of the available literature. The patient's preoperative, intraoperative and postoperative data were recorded. A thorough search through the Google data and Medline to review similar cases or any analyses that referred to ischemic colitis after endovascular abdominal aneurysm repair was conducted. A 76-year-old male was admitted to our department for an elective endovascular repair of an 8 cm in diameter abdominal aortic aneurysm. A Zenith bifurcation graft was implanted. The whole procedure was uneventful and the final angiogram showed an accurate deployment of the endograft without endoleaks and patency of both hypogastric arteries. During the 1st postoperative day, the patient developed symptoms of acute abdomen in combination with metabolic acidosis and oliguria. He underwent an exploratory laparotomy, which revealed necrosis of the sigmoid. A Hartmann's procedure was performed; the patient was transferred to the intensive care unit where he deceased after 24 h. Postoperative ischemic colitis has been described after open abdominal aneurysm repair. The description of this complication has been reported since the early phase of endovascular abdominal aneurysm repair development with a current incidence of 1.5%–3.0%. Possible mechanisms that may contribute to ischemic colitis in spite of the presence of patent hypogastric arteries include atheroembolization, shock, vasopressive drugs and inferior mesenteric artery occlusion.

  8. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

    Science.gov (United States)

    Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

    2016-05-27

    Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Successful treatment of ulcerative colitis complicated by Sweet's syndrome by corticosteroid therapy and leukocytapheresis.

    Science.gov (United States)

    Terai, Tomohiro; Sugimoto, Mitsushige; Osawa, Satoshi; Sugimoto, Ken; Furuta, Takahisa; Kanaoka, Shigeru; Ikuma, Mutsuhiro

    2011-06-01

    Ulcerative colitis is occasionally complicated by dermatological disorders presenting as extra-intestinal manifestations, including erythema nodosum and pyoderma gangrenosum. Sweet's syndrome is considered to be a rare cutaneous disease in patients with ulcerative colitis. To date, only 17 cases of Sweet's syndrome complicating ulcerative colitis have been reported in the English literature. Here, we report a case of a 41-year-old male who had been suffering from ulcerative colitis for 20 years. He was admitted to hospital with hematochezia, diarrhea and fever, and painful erythematous nodules on the face and arms. Histological examination of skin biopsies showed inflammatory cell infiltration composed mainly of neutrophils without evidence of necrotizing vasculitis, and the condition was diagnosed as Sweet's syndrome. The patient was treated with prednisolone and leukocytapheresis and the erythematous nodules on the skin, as well as the abdominal symptoms and endoscopic findings of ulcerative colitis, immediately improved. In this paper we report on this case and review the literature concerning ulcerative colitis and Sweet's syndrome.

  10. Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats

    DEFF Research Database (Denmark)

    Di Marco, Roberto; Mangano, Katia; Quattrocchi, Cinzia

    2003-01-01

    Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves....... These entailed a significant reduction in body weight loss, smaller increase in colon weights, milder macroscopic damage, and lower histological scores. In addition, when sacrificed at the end of the study, fusidin-treated rats had significantly lower blood levels of tumor necrosis factor alpha and interferon......-gamma compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD....

  11. Reactive arthritis induced by recurrent Clostridium difficile colitis

    Directory of Open Access Journals (Sweden)

    Allison Marr

    2012-01-01

    Full Text Available Clostridium difficile colitis is a common infection that can be difficult to resolve and may result in recurrent infections. Reactive arthritis is a rare presentation of this disease and its treatment is not well differentiated in the literature. We describe a case of reactive arthritis occurring in a patient with a history of recurrent Clostridium difficile colitis while currently receiving a taper of oral vancomycin. His arthritis symptoms resolved with corticosteroids and continued treatment with anticlostridial antibiotics.

  12. Clostridium difficile Colitis and Neutropenic Fever Associated with Docetaxel Chemotherapy in a Patient with Advanced Extramammary Paget’s Disease

    Directory of Open Access Journals (Sweden)

    Yumi Nonomura

    2012-08-01

    Full Text Available Extramammary Paget's disease is a rare cutaneous malignant neoplasm. Previous studies indicated the efficacy of docetaxel in advanced cases. The common side effects of docetaxel are usually tolerable and seldom life-threatening. We experienced a case of severe pseudomembranous colitis and neutropenic fever that developed just after the first cycle of docetaxel chemotherapy. To the best of our knowledge, there are few reports of pseudomembranous colitis associated with docetaxel administration for skin cancers. The patient showed complete resolution of her symptoms within 2 weeks with an oral metronidazole therapy. During the second and third cycles, the patient received docetaxel safely with lower doses. The present case indicated that pseudomembranous colitis should be included in the differential diagnosis when assessing patients who develop severe diarrhea during systemic chemotherapy with docetaxel.

  13. Ischemic colitis masquerading as colonic tumor, Case report with review of literature

    Institute of Scientific and Technical Information of China (English)

    Parakkal Deepak; Radha Devi

    2011-01-01

    Ischemic colitis can mimic a carcinoma on computed tomographic (CT) imaging or endoscopic examination. A coexisting colonic carcinoma or another potentially obstructing lesion has also been described in 20% of the cases of ischemic colitis. CT scan can differentiate it from colon cancer in 75% of cases. However, colonoscopy is the preferred method for diagnosing ischemic colitis as it allows for direct visualization with tissue sampling. Varied presentations of ischemic colitis have been described as an ulcerated or submucosal mass or as a narrowed segment of colon with ulcerated mucosa on colonoscopy. Awareness and early recognition of such varied presentations of a common condition is necessary to differentiate from a colonic carcinoma, and to avoid unnecessary surgery and related complications.

  14. Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Ruuska, Tarja; Küster, Peter; Grahnquist, Lena

    2016-01-01

    AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric...... ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint...... mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option...

  15. MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

    Directory of Open Access Journals (Sweden)

    Yonghua Bao

    Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

  16. Spontaneous movements of preterm infants is associated with outcome of gross motor development.

    Science.gov (United States)

    Miyagishima, Saori; Asaka, Tadayoshi; Kamatsuka, Kaori; Kozuka, Naoki; Kobayashi, Masaki; Igarashi, Lisa; Hori, Tsukasa; Tsutsumi, Hiroyuki

    2018-04-30

    We conducted a longitudinal cohort study to analyze the relationship between outcome of gross motor development in preterm infants and factors that might affect their development. Preterm infants with a birth weight of antigravity limbs movements by 3D motion capture system at 3 months corrected age. Gross motor developmental outcomes at 6 and 12 months corrected age were evaluated using the Alberta Infant Motor Scale (AIMS). Statistical analysis was carried out by canonical correlation analysis. Eighteen preterm infants were included. In the 6 months corrected age analysis, spontaneous movement had a major effect on Prone and Sitting at 6 months corrected age of AIMS. In the 12 months corrected age analysis, spontaneous movement had a major effect on Sitting and Standing at 12 months corrected age of AIMS. In preterm infants, better antigravity spontaneous movements at 3 months corrected age were significantly correlated with better gross motor development at 6 or 12 months corrected age. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Dietary n-3 PUFA May Attenuate Experimental Colitis

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    Cloé Charpentier

    2018-01-01

    Full Text Available Background. Inflammatory bowel diseases (IBD occurred in genetically predisposed people exposed to environmental triggers. Diet has long been suspected to contribute to the development of IBD. Supplementation with n-3 polyunsaturated fatty acids (PUFA protects against intestinal inflammation in rodent models while clinical trials showed no benefits. We hypothesized that intervention timing is crucial and dietary fatty acid pattern may influence intestinal environment to modify inflammation genesis. The aim of this study was to evaluate the dietary effect of PUFA composition on intestinal inflammation. Methods. Animals received diet varying in their PUFA composition for four weeks before TNBS-induced colitis. Colon inflammatory markers and gut barrier function parameters were assessed. Inflammatory pathway PCR arrays were determined. Results. n-3 diet significantly decreased colon iNOS, COX-2 expression, IL-6 production, and LTB4 production but tended to decrease colon TNFα production (P=0.0617 compared to control diet. Tight junction protein (claudin-1, occludin expressions and MUC2 and TFF3 mRNA levels were not different among groups. n-9 diet also decreased colon IL-6 production (P<0.05. Conclusions. Dietary n-3 PUFA influence colitis development by attenuating inflammatory markers. Further research is required to better define dietary advice with a scientific rationale.

  18. Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis.

    Science.gov (United States)

    Takebayashi, Koichi; Koboziev, Iurii; Ostanin, Dmitry V; Gray, Laura; Karlsson, Fridrik; Robinson-Jackson, Sherry A; Kosloski-Davidson, Melissa; Dooley, Angela Burrows; Zhang, Songlin; Grisham, Matthew B

    2011-01-01

    It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice. Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinβ-deficient (LTβ(-/-) ) mice with RAG(-/-) animals to generate LTβ(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis. We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTβ(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTβ(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTβ(-/-) x RAG(-/-) mice or their littermate controls (LTβ(+/+) x RAG

  19. Colitis ulcerosa idiopática

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    Manuel Sánchez Herrera

    1944-07-01

    IV El prof. Manson-Bahr ratifica plenamente el concepto de los autores de que el enfermo Fideligno Suárez murió de una Colitis Ulcerosa Idiopática con claros signos de neumonía lobar posiblemente neumocóccica.

  20. Appendiceal-sigmoid fistula presenting in a man with ulcerative colitis: a case report

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    Minutolo Vincenzo

    2010-07-01

    Full Text Available Abstract Introduction Ulcerative colitis is a chronic disease characterized by diffuse mucosal inflammation limited to the colon. It mostly affects young adults, yet a large number of middle-aged and older patients with ulcerative colitis have also been reported. Case presentation A 58-year-old Caucasian man presented to our hospital in August 2006 with continuous and diffuse abdominal pain, meteorism, fever and bloody diarrhea. He had a two-year history of ulcerative colitis. Our patient was treated with intravenous medical therapy. As his condition worsened, he underwent surgery. An explorative laparotomy revealed that the entire colon was distended and pus was found around an appendiceal-sigmoid fistula. Conclusions Therapy for ulcerative colitis is a rapidly evolving field, with many new biological agents under investigation that are likely to change therapeutic strategies radically in the next decade. Indications for surgery are intractability (49%, stricture, dysplasia, toxic colitis, hemorrhage and perforation. To the best of our knowledge, this is the first case of an appendiceal-sigmoid fistula in a patient affected by ulcerative colitis reported in the literature. Fistulae between the appendix and the sigmoid tract are rarely reported in cases of diverticular disease and appendicitis.

  1. Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

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    June-Chul Lee

    Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

  2. Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy.

    Science.gov (United States)

    Vargas, Thiago Jeunon de Sousa; Fialho, Mônica; Santos, Luiza Tavares dos; Rodrigues, Palmira Assis de Jesus Barreto; Vargas, Ana Luisa Bittencourt Sampaio Jeunon; Sousa, Maria Auxiliadora Jeunon

    2013-01-01

    Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.

  3. Initial experience with golimumab in clinical practice for ulcerative colitis

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    Luisa Castro-Laria

    Full Text Available Background: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis. Purpose: To research the effectiveness and safety of golimumab in patients with ulcerative colitis in clinical practice. Methods: Retrospective study of the effectiveness and safety of golimumab in patients with ulcerative colitis. All patients received golimumab 200 mg subcutaneously at week 0, and golimumab 100 mg subcutaneously at week 2. After the induction treatment, each patient received 50 mg sc. every 4 weeks in patients with body weight less than 80 kg, and 100 mg every 4 weeks in patients with body weight greater than or equal to 80 kg. Results: Study of a group of 23 ulcerative colitis patients, 7 of whom were naive to any anti-TNF therapy, and 16 patients who had previously been treated with an anti-TNF agent other than golimumab (non-naive patients. The average treatment time with golimumab was 14.3 weeks. Globally, withdrawal of corticosteroids was observed in 74% of cases. Clinical response was observed in 85.5% of patients who had not received biological treatment previously, and in patients who had previously received biological treatment the response rate was 75%. Conclusions: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients. It is also a safe therapy, given that there were no adverse effects in the patients studied.

  4. Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice.

    Science.gov (United States)

    Jauch, Dominik; Martin, Maria; Schiechl, Gabriela; Kesselring, Rebecca; Schlitt, Hans Jürgen; Geissler, Edward K; Fichtner-Feigl, Stefan

    2011-12-01

    Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Chronic colitis was induced in IL-21(-/-) and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and therefore limited tumour growth. These results indicate that IL-21

  5. Pas de Deux: Active Ulcerative Colitis in an HIV-Positive Patient

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    David C Pearson

    1996-01-01

    Full Text Available A 40-year-old male who was found to be human immunodeficiency virus-positive when he presented with bloody diarrhea in 1986 is described. Clinical, laboratory, endoscopic and histological findings were all compatible with ulcerative colitis, and stool cultures were repeatedly negative for pathogens. Colitis was initially mild and controlled with intermittent oral aminosalicylic acid products. Since 1993 he has had more significant symptoms requiring prednisone up to 40 mg/day. Repeat colonoscopy disclosed pancolitis and biopsies did not show evidence of cytomegalovirus infection. He has not had an acquired immune deficiency syndrome-defining illness. CD4 cells fell below normal as his colitis worsened. This case raises questions about immune regulation in ulcerative colitis because the patient has active disease in addition to a reduced number of T helper cells. It also presents a difficult management problem because the patient has a limited life expectancy and is reluctant to accept colectomy, and further immunosuppressive therapy may be dangerous.

  6. The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in rats.

    Science.gov (United States)

    Genc, Zeynep; Yarat, Aysen; Tunali-Akbay, Tugba; Sener, Goksel; Cetinel, Sule; Pisiriciler, Rabia; Caliskan-Ak, Esin; Altıntas, Ayhan; Demirci, Betul

    2011-12-01

    This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.

  7. Adoptive transfer of immune enhancement of experimental ulcerative colitis.

    OpenAIRE

    Onderdonk, A B; Steeves, R M; Cisneros, R L; Bronson, R T

    1984-01-01

    Previous experiments with the carrageenan model for ulcerative colitis have shown that the inflammatory response in guinea pigs can be enhanced by immunization with and subsequent feeding of Bacteroides vulgatus to experimental animals. The present studies showed that only certain strains of B. vulgatus are capable of provoking immune enhancement of ulcerative colitis. Animals were fed carrageenan and various strains of viable B. vulgatus after immunization with a strain of B. vulgatus isolat...

  8. Management of pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Turner, Dan; Levine, Arie; Escher, Johanna C

    2012-01-01

    Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR...

  9. The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

    Science.gov (United States)

    Cardoso, Ana; Gil Castro, Antonio; Martins, Ana Catarina; Carriche, Guilhermina M.; Murigneux, Valentine; Castro, Isabel; Cumano, Ana; Vieira, Paulo; Saraiva, Margarida

    2018-01-01

    Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. PMID:29545807

  10. Is microscopic colitis a missed diagnosis in diarrhea-predominant Irritable Bowel Syndrome?

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    Hamid Tavakoli

    2008-08-01

    Full Text Available

    • BACKGROUND: There are controversies about the importance of biopsies of normal colon mucosa in the investigation of patients with diarrhea predominant irritable bowel syndrome (IBS. On the other hand, microscopic colitis may bemissed based on normal colonoscopy and laboratory examination in this group of patients
    • METHODS: The study took place in Alzahra and Noor hospitals and Poursina Hakim Research Institute, from 2002 to 2004. Eligible patients were those suffering from diarrhea for at least 4 weeks. A total of 138 patients were included in the study after meeting Rome criteria (II with normal CBC, ESR, stool examination and no endoscopic abnormality.
    • RESULTS: The histologic findings in 138 patients with diarrhea predominant IBS with mean age of 34.7 years (female 55.1% and male 44.9% were as follows: 10 patients (7.2% had collagenous colitis and 3 patients (2.2% were compatible with lymphocytic colitis. No significant diagnostic histologic findings were seen in the rest of patients. Collagenouscolitis was detected in 13% of right colon biopsies and in 10% of sigmoid and transverse colon biopsies. Nocturnal diarrhea was found in 30% of collagenous colitis patients.
    • CONCLUSIONS: Total colonoscopy and multiple biopsies in diarrhea predominant IBS patients are necessary for earlydiagnosis of microscopic colitis.
    • KEY WORDS: Irritable bowel syndrome, microscopic colitis, colonoscopy, biopsy, diarrhea.

  11. The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

    Science.gov (United States)

    Cipriani, Sabrina; Mencarelli, Andrea; Chini, Maria Giovanna; Distrutti, Eleonora; Renga, Barbara; Bifulco, Giuseppe; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

    2011-01-01

    Background GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods Colitis was induced in wild type and GP-BAR1−/− mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results GP-BAR1−/− mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. PMID:22046243

  12. The bile acid receptor GPBAR-1 (TGR5 modulates integrity of intestinal barrier and immune response to experimental colitis.

    Directory of Open Access Journals (Sweden)

    Sabrina Cipriani

    Full Text Available BACKGROUND: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. AIMS: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. METHODS: Colitis was induced in wild type and GP-BAR1(-/- mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. RESULTS: GP-BAR1(-/- mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. CONCLUSIONS: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand.

  13. BODY COMPOSITION IN PATIENTS WITH CROHN’S DISEASE AND ULCERATIVE COLITIS

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    Ivi Ribeiro BACK

    2017-03-01

    Full Text Available ABSTRACT BACKGROUND The nutritional status of individuals with inflammatory bowel diseases is directly related to the severity of the disease and is associated with poor prognosis and the deterioration of immune competence. OBJECTIVE To assess the nutritional status and the body composition of outpatients with inflammatory bowel diseases. METHODS A cross-sectional study was conducted with clinical and nutritional assessment of patients with Crohn’s disease and ulcerative colitis. Patients were classified according to the clinical activity through Crohn’s Disease Activity Index and Mayo Score. Nutritional assessment consisted of anthropometric measurements of current weight, height, mid-arm circumference, triceps skinfold thickness and thickness of adductor policis muscle, with subsequent calculation of BMI, arm muscle circumference and the mid-arm muscle area (MAMA. The phase angle (PhA and lean and fat mass were obtained with the use of electrical bioimpedance. Descriptive statistics, chi-square test or Fisher exact test, ANOVA and t-test. RESULTS We evaluated 141 patients of which 54 (38.29% had Crohn’s disease and 87 (61.70% ulcerative colitis. The mean age was 43.98 (±15.68 years in Crohn’s disease and 44.28 (±16.29 years for ulcerative colitis. Most of the patients were in clinical remission of the disease (Crohn’s disease: 88.89%; ulcerative colitis: 87.36%. Regarding the nutritional classification using BMI, it was found that 48.15% of Crohn’s disease patients were eutrophic and 40.74% were overweight or obese; among patients with ulcerative colitis, 52.87% were classified as overweight or obese. When considering the triceps skinfold, it was observed in both groups a high percentage of overweight and obesity (Crohn’s disease: 75.93%; ulcerative colitis: 72.42%. Crohn’s disease patients showed the most affected nutritional status according to the nutritional variables when compared to patients with ulcerative colitis (BMI

  14. Tetraspanin CD9 Limits Mucosal Healing in Experimental Colitis

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    María Laura Saiz

    2017-12-01

    Full Text Available Tetraspanins are a family of proteins with four transmembrane domains that associate between themselves and cluster with other partner proteins, conforming a distinct class of membrane domains, the tetraspanin-enriched microdomains (TEMs. These TEMs constitute macromolecular signaling platforms that regulate key processes in several cellular settings controlling signaling thresholds and avidity of receptors. In this study, we investigated the role of CD9, a tetraspanin that regulates major biological processes such as cell migration and immunological responses, in two mouse models of colitis that have been used to study the pathogenesis of inflammatory bowel disease (IBD. Previous in vitro studies revealed an important role in the interaction of leukocytes with inflamed endothelium, but in vivo evidence of the involvement of CD9 in inflammatory diseases is scarce. Here, we studied the role of CD9 in the pathogenesis of colitis in vivo. Colitis was induced by administration of dextran sodium sulfate (DSS, a chemical colitogen that causes epithelial disruption and intestinal inflammation. CD9−/− mice showed less severe colitis than wild-type counterparts upon exposure to DSS (2% solution and enhanced survival in response to a lethal DSS dose (4%. Decreased neutrophil and macrophage cell infiltration was observed in colonic tissue from CD9−/− animals, in accordance with their lower serum levels of TNF-α, IL-6, and other proinflammatory cytokines in the colon. The specific role of CD9 in IBD was further dissected by transfer of CD4+ CD45RBhi naive T cells into the Rag1−/− mouse colitis model. However, no significant differences were observed in these settings between both groups, ruling out a role for CD9 in IBD in the lymphoid compartment. Experiments with bone marrow chimeras revealed that CD9 in the non-hematopoietic compartment is involved in colon injury and limits the proliferation of epithelial cells. Our data indicate that CD9

  15. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis.

    Science.gov (United States)

    Sandborn, William J; Targan, Stephan R; Byers, Vera S; Rutty, Dean A; Mu, Hua; Zhang, Xun; Tang, Tom

    2013-01-01

    Andrographis paniculata has in vitro inhibitory activity against TNF-α, IL-1β and NF-κB. A pilot study of A. paniculata extract (HMPL-004) suggested similar efficacy to mesalamine for ulcerative colitis. A randomized, double-blind, placebo-controlled trial evaluated the efficacy of A. paniculata extract (HMPL-004) in 224 adults with mild-to-moderate ulcerative colitis. Patients were randomized to A. paniculata extract (HMPL-004) 1,200 mg or 1,800 mg daily or placebo for 8 weeks. In total, 45 and 60% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical response at week 8, compared with 40% of those who received placebo (P=0.5924 for 1,200 mg vs. placebo and P=0.0183 for 1,800 mg vs. placebo). In all, 34 and 38% of patients receiving A. paniculata 1,200 mg and 1,800 mg daily, respectively, were in clinical remission at week 8, compared with 25% of those who received placebo (P=0.2582 for 1,200 mg vs. placebo and P=0.1011 for 1,800 mg vs. placebo). Adverse events developed in 60 and 53% of patients in the A. paniculata 1,200 mg and 1,800 mg daily groups, respectively, and 60% in the placebo group. Patients with mildly to moderately active ulcerative colitis treated with A. paniculata extract (HMPL-004) at a dose of 1,800 mg daily were more likely to achieve clinical response than those receiving placebo.

  16. In vivo assessment of 111In labelled lymphocyte gut homing in a TNBS colitis mouse model determined by dedicated animal pinhole SPECT

    International Nuclear Information System (INIS)

    Bennink, R.J.; Bruin, C.M. de; Montfrans, C. van; Jonge, W.J. de; Deventer, S.J. van; Velde, A.A. te

    2002-01-01

    Aims: The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD. Materials and Methods: TNBS sensitised and non-sensitised murine total splenocytes, isolated from donor TNBS colitis or placebo treated BALB/c mice, were labelled in vitro with 111 In-oxine and injected intravenously into recipient BALB/c mice with TNBS-induced colitis or healthy BALB/c mice instilled with saline. Biodistribution and specific radioactive uptake, representing transferred cells, was determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labelled cells. Moreover, the severity of inflammation in recipient mice was determined by histological scoring. Results: Lymphocyte migration to the inflamed colon of recipient mice increased in time and was maximal at 48h after administration of the 111 In-oxine labelled donor splenocytes. The highest specific radioactive uptake ratio in the colon after 48h was observed in recipient mice with TNBS colitis that received TNBS sensitised lymphocytes (saline vs. TNBS colitis resp. 0.22 ± 0.035 and 0.51 ± 0.033 mean ± SEM p<0.01). Histological scoring confirmed colitis in the TNBS colitis recipient groups and excluded colitis in the saline instilled recipient groups. TNBS colitis recipient mice that received sensitised lymphocytes had a more severe colitis upon histological evaluation as compared with TNBS colitis recipient mice receiving non-sensitised cells (mean histological

  17. Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

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    Lifu Wang

    2017-09-01

    Full Text Available Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes would be useful for treating inflammatory bowel disease (IBD. Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS in drinking water (5.0%, wt/vol. Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD.

  18. The application of molecular topology for ulcerative colitis drug discovery.

    Science.gov (United States)

    Bellera, Carolina L; Di Ianni, Mauricio E; Talevi, Alan

    2018-01-01

    Although the therapeutic arsenal against ulcerative colitis has greatly expanded (including the revolutionary advent of biologics), there remain patients who are refractory to current medications while the safety of the available therapeutics could also be improved. Molecular topology provides a theoretic framework for the discovery of new therapeutic agents in a very efficient manner, and its applications in the field of ulcerative colitis have slowly begun to flourish. Areas covered: After discussing the basics of molecular topology, the authors review QSAR models focusing on validated targets for the treatment of ulcerative colitis, entirely or partially based on topological descriptors. Expert opinion: The application of molecular topology to ulcerative colitis drug discovery is still very limited, and many of the existing reports seem to be strictly theoretic, with no experimental validation or practical applications. Interestingly, mechanism-independent models based on phenotypic responses have recently been reported. Such models are in agreement with the recent interest raised by network pharmacology as a potential solution for complex disorders. These and other similar studies applying molecular topology suggest that some therapeutic categories may present a 'topological pattern' that goes beyond a specific mechanism of action.

  19. Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients with ulcerative colitis: the old and new evidence.

    Science.gov (United States)

    Diculescu, Mircea; Ciocîrlan, Mihai; Ciocîrlan, Mirela; Piţigoi, Dan; Becheanu, Gabriel; Croitoru, Adina; Spanache, Sandu

    2003-12-01

    The purpose of the study was to assess whether folic acid supplementation and long term therapy with sulfasalazine can reduce the risk of colorectal cancer (CRC) development in longstanding extensive ulcerative colitis. A meta-analysis was performed including the last 10 years published and Medline indexed studies on this subject. 3 studies have been included concerning the protective effect of folate supplementation in development of CRC. The association of these two factors is significant (effect size r =0.124, p = 0.025). The fail-safe number of studies with an opposite result should be 4 to revert the significance. 4 studies regarding sulfasalazine's protective effect in longstanding extensive ulcerative colitis have also been evaluated. A similar significance has been obtained, r = 0.148, p = 0.0007 and a fail-safe number of studies equal to 7. The homogeneity of these studies is validated by standard tests. Both sulfasalazine therapy and folate supplementation have a protective effect in colorectal cancer development in a population of patients with longstanding ulcerative colitis. Randomized controlled trials are needed to explore these hypotheses.

  20. Vanillin improves and prevents trinitrobenzene sulfonic acid-induced colitis in mice.

    Science.gov (United States)

    Wu, Shih-Lu; Chen, Jaw-Chyun; Li, Chia-Cheng; Lo, Hsin-Yi; Ho, Tin-Yun; Hsiang, Chien-Yun

    2009-08-01

    Inflammatory bowel disease (IBD) is chronic inflammatory and relapsing disease of the gut. It has been known that activation of nuclear factor-kappaB (NF-kappaB) and production of proinflammatory cytokines play important roles in the pathogenesis of IBD. In this study, the effect of vanillin (4-hydroxy-3-methoxybenzaldehyde), a potent nuclear factor-kappaB (NF-kappaB) inhibitor, was evaluated in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of vanillin improved macroscopic and histological features of TNBS-induced colitis in a dose-dependent manner. Vanillin not only prevented TNBS-induced colitis but also ameliorated the established colitis. By in vivo NF-kappaB bioluminescence imaging, electrophoretic mobility shift assay, and Western blot, we found that vanillin suppressed in vivo NF-kappaB activities through the inhibition of p65 translocation, inhibitor of nuclear factor-kappaB(IkappaB)-alpha phosphorylation, and IkappaB kinase activation. Furthermore, vanillin reduced the expressions of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, interferon-gamma, and tumor necrosis factor-alpha] and stimulated the expression of anti-inflammatory cytokine (IL-4) in colonic tissues. In conclusion, this work identified vanillin as an anti-inflammatory compound with the capacity to prevent and ameliorate TNBS-induced colitis. Due to its safety, vanillin could be a potent candidate for the treatment of IBD.

  1. Leopard Skin-Like Colonic Mucosa: A Novel Endoscopic Finding of Chronic Granulomatous Disease-Associated Colitis.

    Science.gov (United States)

    Obayashi, Naho; Arai, Katsuhiro; Nakano, Natsuko; Mizukami, Tomoyuki; Kawai, Toshinao; Yamamoto, Shojiro; Shimizu, Hirotaka; Nunoi, Hiroyuki; Shimizu, Toshiaki; Tang, Julian; Onodera, Masafumi

    2016-01-01

    Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes are unable to eradicate pathogens because of a deficit of nicotinamide adenine dinucleotide phosphate oxidase. Among CGD patients, ∼ 30% to 50% develop severe gastrointestinal tract symptoms. Although characteristic histologic findings of CGD-associated colitis have been reported, information on endoscopic features remained vague. A total of 8 male patients with CGD (ages 2-23 years) from 2 Japanese institutions underwent colonoscopy for the evaluation of their fever, diarrhea, bloody stool, and abdominal pain. The endoscopic and histologic findings were retrospectively reviewed. The endoscopic findings of CGD-associated colitis appeared varied. Notably, brownish dots over a yellowish edematous mucosa were observed in 3 of the 8 patients. Prominent pigment-laden macrophages were noted histologically on the mucosa. Although nonspecific endoscopic findings of CGD-associated colitis have been reported before, our observation of brownish dots spread across a yellowish edematous mucosa, termed "leopard sign," could be a unique feature of this condition.

  2. Membranous nephropathy associated with familial chronic ulcerative colitis in a 12-year-old girl.

    Science.gov (United States)

    Ridder, Regina M; Kreth, Hans W; Kiss, Eva; Gröne, Hermann J; Gordjani, Nader

    2005-09-01

    Glomerulonephritis is a rare complication in patients with inflammatory bowel disease. We report a case of membranous nephropathy (MN) in a 12.6-year-old girl with chronic ulcerative colitis. The girl was referred to the hospital with bloody diarrhea and arthralgia. Routine urinalysis showed 1 g/m(2) protein excretion in 24 h. Serum ANCA titers were positive. The diagnoses were confirmed by coloscopy and kidney biopsy. The patient's mother had also suffered from ulcerative colitis in adolescence. Proteinuria normalized under treatment with prednisone (60 mg/m(2)/day) and azathioprine, which was initiated to treat the colitis. Chronic ulcerative colitis can be associated with glomerulonephritis.

  3. THE CLINICAL SPECTRUM OF AMOEBIC COLITIS*

    African Journals Online (AJOL)

    1971-02-27

    Feb 27, 1971 ... The clinical presentation of acute amoebic colitis and its ... Case 1. A 35-year-old Coloured male presented to the. Medical Outpatient Department with a 2-week ..... necessitate emergency colectomy. ... tion and peritonitis.

  4. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

    Science.gov (United States)

    Griseri, Thibault; Arnold, Isabelle C.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S.; Crocker, Paul R.; Powrie, Fiona

    2015-01-01

    Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

  5. Clostridium difficile Colitis and Neutropenic Fever Associated with Docetaxel Chemotherapy in a Patient with Advanced Extramammary Paget’s Disease

    OpenAIRE

    Nonomura, Yumi; Otsuka, Atsushi; Endo, Yuichiro; Fujisawa, Akihiro; Tanioka, Miki; Kabashima, Kenji; Miyachi, Yoshiki

    2012-01-01

    Extramammary Paget's disease is a rare cutaneous malignant neoplasm. Previous studies indicated the efficacy of docetaxel in advanced cases. The common side effects of docetaxel are usually tolerable and seldom life-threatening. We experienced a case of severe pseudomembranous colitis and neutropenic fever that developed just after the first cycle of docetaxel chemotherapy. To the best of our knowledge, there are few reports of pseudomembranous colitis associated with docetaxel administration...

  6. Perforation in a patient with stercoral colitis and diverticulosis: who did it?

    Directory of Open Access Journals (Sweden)

    Vijaya R. Bhatt

    2014-02-01

    Full Text Available Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis has not been discussed. We, therefore, report this case of stercoral perforation in a patient with diverticulosis and include a discussion of the epidemiology, clinical presentation, and a review of helpful diagnostic clues for a rapid differentiation to allow for accurate diagnosis and treatment.

  7. Apple polyphenols extract (APE) improves colon damage in a rat model of colitis.

    Science.gov (United States)

    D'Argenio, Giuseppe; Mazzone, Giovanna; Tuccillo, Concetta; Ribecco, Maria T; Graziani, Giulia; Gravina, Antonietta G; Caserta, Sergio; Guido, Stefano; Fogliano, Vincenzo; Caporaso, Nicola; Romano, Marco

    2012-07-01

    Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (pApple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase. The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Synchronous cytomegalovirus infection in a newly diagnosed ulcerative colitis patient

    Directory of Open Access Journals (Sweden)

    Jin Yu Chieng

    2017-12-01

    Full Text Available A 61-year-old Punjabi female patient presented with six months history of mild abdominal discomfort with bloody diarrhea. She did not have underlying chronic medical illness; she neither took steroid nor immunosuppressant. She was found anemic, thrombocytosis, and elevated C-reactive protein. Colonoscopy showed moderate left sided colitis, with histopathology evidence of ulcerative colitis (UC with cytomegalovirus (CMV infection. Her serum anti-CMV IgM antibody was detected. She was treated with intravenous ganciclovir, together with 5-ASA and tapering dose of steroid. Anemia was corrected. Subsequent clinic reviews and follow up endoscopies showed dramatically improvement. CMV colitis should be considered for the patients presenting with moderate to severe UC. Early prescription of antiviral would be beneficial in the treatment of flare of UC.

  9. Induction of colitis in young rats by dextran sulfate sodium.

    Science.gov (United States)

    Vicario, María; Crespí, Mar; Franch, Angels; Amat, Concepció; Pelegrí, Carme; Moretó, Miquel

    2005-01-01

    Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

  10. Diverticular Disease-associated Colitis: What Do We Know? A Review of Literature.

    Science.gov (United States)

    Haddad, Fady G; El Bitar, Sandy; Al Moussawi, Hassan; Chang, Qing; Deeb, Liliane

    2018-02-24

    Diverticular disease (DD) is a leading cause of hospitalizations in developed countries affecting 30-50% of individuals older than 60 years. Identified as a distinct entity since 1980, diverticular disease-associated colitis (DAC) describes the occurrence of mucosal inflammation in a colon segment affected with DD with relative sparing of the rectum and proximal colon. Its prevalence is suggested around 1.3-3.8%. Pathogenesis is multifactorial with multiple reports noting clinicopathological overlap between DAC and inflammatory bowel disease (IBD) especially in patients with granulomatous colitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of IBD. Recurrence rates and long-term outcomes of DAC are not well defined and could range from a benign course to an overt IBD. More studies are needed in order to further characterize this entity.

  11. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

    2013-01-01

    Ulcerative colitis (UC) is a colonic inflammatory condition with a substantial impact on the quality of life of affected persons. The disease carries a cumulative risk of need of colectomy of 20-30% and an estimated cumulative risk of colorectal cancer of 18% after 30 years of disease duration. W...

  12. Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

    Science.gov (United States)

    Al-Awadi, F M; Srikumar, T S; Anim, J T; Khan, I

    2001-05-01

    Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

  13. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

    Science.gov (United States)

    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  14. The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Ana Cardoso

    2018-03-01

    Full Text Available Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10, described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.

  15. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

    Science.gov (United States)

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-10-31

    Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  16. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    Directory of Open Access Journals (Sweden)

    Ando Tomoaki

    2005-10-01

    Full Text Available Abstract Genetic deficiency in the expression of interleukin-10 (IL-10 is associated with the onset and progression of experimental inflammatory bowel disease (IBD. The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10, an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate, a common model of colitis. Adenoviral IL-10 (Ad-IL10 transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS, Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10 gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  17. Automated image analysis in the study of collagenous colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Kristensson, Martin; Engel, Ulla

    2016-01-01

    PURPOSE: The aim of this study was to develop an automated image analysis software to measure the thickness of the subepithelial collagenous band in colon biopsies with collagenous colitis (CC) and incomplete CC (CCi). The software measures the thickness of the collagenous band on microscopic...... slides stained with Van Gieson (VG). PATIENTS AND METHODS: A training set consisting of ten biopsies diagnosed as CC, CCi, and normal colon mucosa was used to develop the automated image analysis (VG app) to match the assessment by a pathologist. The study set consisted of biopsies from 75 patients...

  18. Data on IL-10R neutralization-induced chronic colitis in Lipocalin 2 deficient mice on BALB/c background

    Directory of Open Access Journals (Sweden)

    Vishal Singh

    2017-04-01

    Full Text Available The data herein is related to the research article entitled “Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis” (Singh et al., 2016 [1] where we have demonstrated that C57BL/6 Lipocalin 2 deficient mice (Lcn2KO developed chronic colitis upon anti-interleukin-10 receptor (αIL-10R monoclonal antibody administration. In the present article, we evaluated the susceptibility of BALB/c Lcn2KO mice and their WT littermates to the αIL-10R neutralization-induced chronic colitis. Our data showed that αIL-10R mAb-treated BALB/c Lcn2KO mice exhibited severe chronic colitis (i.e., splenomegaly, colomegaly, colonic pathology, and incidence of rectal prolapse when compared to WT mice.

  19. Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies.

    Science.gov (United States)

    Lakatos, Peter-Laszlo; Lakatos, Laszlo

    2008-07-07

    The risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

  20. Tratamientos más utilizados en la colitis ulcerativa

    OpenAIRE

    Daisy Carbajal-Quintana

    2015-01-01

    Teniendo en cuenta la importancia de la colitis ulcerativa, el objetivo de esta revisión consiste en la aproximación al manejo de enfermedad haciendo énfasis en los tratamientos. La colitis ulcerativa (CU) es una enfermedad inflamatoria crónica caracterizada por la inflamación de la mucosa del colon y el recto. Es una enfermedad multifactorial, con una interacción compleja de factores genéticos y ambientales. Los síntomas más frecuentes son diarrea, dolor abdominal y...

  1. Therapeutic action of ghrelin in a mouse model of colitis.

    Science.gov (United States)

    Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

    2006-05-01

    Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

  2. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Kirchgessner Annette

    2011-08-01

    Full Text Available Abstract Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

  3. Prebiotics and synbiotics in ulcerative colitis.

    Science.gov (United States)

    Laurell, Axel; Sjöberg, Klas

    2017-04-01

    Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with unclear pathogenesis. A dysbiotic intestinal microbiota is regarded as a key component in the disease process and there has been significant interest in developing new treatments which target the microbiota. To give an overview of the studies to date investigating prebiotics and synbiotics for the treatment of UC. A literature search of PubMed and related search engines was carried out using the terms "ulcerative colitis" in combination with "prebiotic", "synbiotic" or "dietary fibre". In total 17 studies on humans examining the effect of prebiotics in UC were found. Five major groups could be distinguished. Fructo-oligosaccharides were tried in six studies (mean 35 patients included, range 9-121). One study found a clinical response while two demonstrated indirect evidence of an effect. Germinated barley foodstuff was used in 8 studies (mean 38 patients, range 10-63). One study found an endoscopic response, while four noted a clinical response and two some indirect effects. Galacto-oligosaccharides, lactulose and resveratrol were used in one study each (mean 48 patients, range 41-52). One study found an endoscopic response and one a clinical response. There is yet inadequate evidence - especially in humans - to support any particular prebiotic in the clinical management of UC. However, due to the bulk of evidence supporting the effect of the microbiota on colonic inflammation, there is enough potential to justify further high-quality clinical trials investigating this subject.

  4. Tenosynovitis of the ankles as onset of sarcoidosis in a patient with ulcerative colitis

    OpenAIRE

    F. Cozzi; M. Podswiadek; A. Furlan; S. Todesco

    2011-01-01

    Arthritis and tenosynovitis are frequently reported as complications of inflammatory bowel diseases. About 10% of patients with ulcerative colitis presents articular inflammation, usually in the phases of activity of intestinal disease. Tenosynovitis is also a frequent complication of ulcerative colitis. We describe here a case of tenosynovitis of both ankles occurring in a patient affected by ulcerative colitis not in active phase. Chest X-ray and TC showed hilar lymphonode enlargement and t...

  5. Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

    International Nuclear Information System (INIS)

    Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

    2008-01-01

    Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

  6. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Peris Mumbi Munyaka

    Full Text Available Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

  7. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

    Science.gov (United States)

    Munyaka, Peris Mumbi; Eissa, N; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

    2015-01-01

    Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

  8. Development of gut inflammation in mice colonized with mucosa-associated bacteria from patients with ulcerative colitis

    Czech Academy of Sciences Publication Activity Database

    Du, Z.; Hudcovic, T.; Mrázek, J.; Kozáková, H.; Šrůtková, D.; Schwarzer, M.; Tlaskalová-Hogenová, H.; Kostovčík, M.; Kverka, Miloslav

    2015-01-01

    Roč. 7, dec 21 (2015), s. 32 ISSN 1757-4749 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP303/12/0535 Institutional support: RVO:68378041 Keywords : dysbiosis * microbiota * germ-free mice * ulcerative colitis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.816, year: 2015

  9. Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

    OpenAIRE

    Souza, Patrícia Reis de; Sales-Campos, Helioswilton; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda; Alves, Vanessa Beatriz Freitas; Chica, Javier Emílio Lazo; Nomizo, Auro; Cardoso, Cristina Ribeiro de Barros

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score...

  10. Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

    DEFF Research Database (Denmark)

    Gad, Monika; Kristensen, Nanna N; Kury, Evelyn

    2004-01-01

    -injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells offered no protection against...

  11. IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding

    2015-01-01

    of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 -/- mice, dextran sodium sulfate (DSS) model) and UC.METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells...

  12. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  13. Update on the surgical management of ulcerative colitis and ulcerative proctitis: current controversies and problems.

    Science.gov (United States)

    Sagar, P M; Pemberton, J H

    1995-01-01

    : The surgical management of ulcerative colitis has been revolutionized in recent years by the development of the ileal pouch-anal procedure. Although it is now the operation of choice for most patients, there remain several controversies. A variety of designs of ileal pouch are available each with advantages and disadvantages. The technique used to anastomose the pouch to the anal canal is also open to debate with some surgeons favoring distal mucosectomy with eradication of all disease and others choosing to perform a stapled anastomosis to achieve better functional results. The main concern for gastroenterologists, however, is the risk of development of pouchitis. The etiology, diagnosis, and treatment of this condition will also be discussed in this review as well as the more classical options for the surgical treatment of ulcerative colitis.

  14. Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice

    DEFF Research Database (Denmark)

    Kjellev, Stine; Thim, Lars; Pyke, Charles

    2007-01-01

    the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma......-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3...... was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal...

  15. Safety and efficacy of Profermin(R) to induce remission in ulcerative colitis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Israelsen, Hans; von Ryberg, Bjørn

    2012-01-01

    AIM: To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC). METHODS: The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treated ope...

  16. [Changes of expression of miR-155 in colitis-associated colonic carcinogenesis].

    Science.gov (United States)

    Li, Weiwei; Han, Wenxiao; Zhao, Xinhua; Wang, Hongying

    2014-04-01

    To investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis. Colitis-associated colon cancer was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice of three different stages during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment and a DSS only group representing chronic inflammation without cancer were set up as well. Colon tissue was collected and expression of miR-155 in the colon tissues was measured by real-time fluorescent quantitative PCR. TargetScan and PicTar were used to predict potential target genes of miR-155, which were then preliminarily screened with our gene expression microarray database of AOM-DSS mouse model. Regular PCR was used to confirm the changes of the expression of these potential target genes in AOM-DSS mouse model. Colitis-associated colon cancer was effectively induced by azoxymethane and dextran sulfate sodium in C57BL/6 mice. Histological examination revealed that the evolution process was sequentially from normal, mild dysplasia, moderate dysplasia, and severe dysplasia to adenocarcinoma in the AOM-DSS mouse model. The level of miR-155 was gradually elevated with the formation of colitis-associated colon cancer. There was no significant difference between the levels of miR-155 expression in the DSS group (0.005 6 ± 0.003 7) and control group (0.012 0 ± 0.005 1) (P > 0.05), but the level of miR-155 in the AD3 group (0.054 4 ± 0.027 0) was significantly higher than that of the DSS group (0.005 6 ± 0.003 7)(P Bcorl1, Cacna1c, Rspo2 and Foxo3 were potential target genes of miR-155 in the AOM-DSS mouse model. Changes of Kcna1 and Cacna1c in the AOM-DSS mouse model were validated to be consistent with the changes obtained with the gene expression microarray. The up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the

  17. Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus.

    Science.gov (United States)

    Shi, Yulin; Ikrar, Taruna; Olivas, Nicholas D; Xu, Xiangmin

    2014-06-15

    Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  18. Paradoxical Impact of Ileal Pouch-Anal Anastomosis on Male and Female Fertility in Patients With Ulcerative Colitis.

    Science.gov (United States)

    Pachler, Frederik R; Brandsborg, Søren B; Laurberg, Søren

    2017-06-01

    Birth rates in males with ulcerative colitis and ileal pouch-anal anastomosis have not been studied. This study aimed to estimate birth rates in males and females with ulcerative colitis and study the impact of ileal pouch-anal anastomosis. This was a retrospective registry-based cohort study that was performed over a 30-year period. Records for parenting a child from the same period were cross-linked with patient records, and birth rates were calculated using 15 through 49 years as age limits. All data were prospectively registered. All patients with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis between 1980 and 2010 were identified in Danish national databases. The primary outcomes measured were birth rates in females and males with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis. We included 27,379 patients with ulcerative colitis (12,812 males and 14,567 females); 1544 had ileal pouch-anal anastomosis (792 males and 752 females). Patients with ulcerative colitis have slightly reduced birth rates (males at 40.8 children/1000 years, background population 43.2, females at 46.2 children/1000 years, background population 49.1). After ileal pouch-anal anastomosis, males had increased birth rates at 47.8 children/1000 years in comparison with males with ulcerative colitis without ileal pouch-anal anastomosis (40.5 children/1000 years), whereas females had reduced birth rates at 27.6 children/1000 years in comparison with females with ulcerative colitis without ileal pouch-anal anastomosis (46.8 children/1000 years). Only birth rates were investigated and not fecundability. Furthermore, there is a question about misattributed paternity, but this has previously been shown to be less than 5%. Ulcerative colitis per se has little impact on birth rates in both sexes, but ileal pouch-anal anastomosis surgery leads to a reduction in birth rates in females and an increase in birth rates in males. This has clinical

  19. Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

    2012-01-01

    We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activatio...

  20. Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

    2012-01-01

    We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activation...

  1. Genome-wide expression profiling during protection from colitis by regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Olsen, Jørgen; Gad, Monika

    2008-01-01

    BACKGROUND: In the adoptive transfer model of colitis it has been shown that regulatory T cells (Treg) can hinder disease development and cure already existing mild colitis. The mechanisms underlying this regulatory effect of CD4(+)CD25(+) Tregs are not well understood. METHODS: To identify......Chip Mouse Genome 430 2.0 Array), which enabled an analysis of a complete set of RNA transcript levels in each sample. Array results were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Data were analyzed using combined projections to latent structures and functional...... annotation analysis. The colitic samples were clearly distinguishable from samples from normal mice by a vast number of inflammation- and growth factor-related transcripts. In contrast, the Treg-protected animals could not be distinguished from either the normal BALB/c mice or the normal SCID mice. mRNA...

  2. Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3+ regulatory T cells

    International Nuclear Information System (INIS)

    Mitsui, Toshihito; Sashinami, Hiroshi; Sato, Fuyuki; Kijima, Hiroshi; Ishiguro, Yoh; Fukuda, Shinsaku; Yoshihara, Shuichi; Hakamada, Ken-Ichi; Nakane, Akio

    2010-01-01

    Research highlights: → Salmon proteoglycan suppresses IL-10 -/- cell transfer-induced colitis progression. → Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. → Salmon proteoglycan enhances Foxp3 expression. -- Abstract: Proteoglycans (PGs) are complex glycohydrates which are widely distributed in extracellular matrix (ECM). PGs are involved in the construction of ECM, cell proliferation and differentiation. ECM components are involved in transduction of proinflammatory responses, but it is still unknown whether PGs are involved in inflammatory response. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis-induced in severe combined immunodeficiency mice by cell transfer from interleukin-10 (IL-10) -/- mice. IL-10 -/- cell-transferred mice showed weight loss, colon shortening and histological appearance of mild colitis. Daily oral administration of PG attenuated the clinical progression of colitis in a dose-dependent manner. Colitis-induced mice showed the elevated expression of IFN-γ, IL-12, TNF-α, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor γt (RORγt) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4 + CD25 + regulatory T cells in LPMCs was enhanced by PG administration. These findings suggested that salmon PG attenuated the progression of colitis due to suppression of inflammatory response by enhancement of regulatory T cell induction.

  3. The Rhizome Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates Mesalazine-Resistant Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Su-Min Lim

    2016-01-01

    Full Text Available We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS- induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC. Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg and DWac (15 mg/kg additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine.

  4. Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

    Science.gov (United States)

    Brown, Kirsty; Rajendiran, Ethendhar; Estaki, Mehrbod; Dai, Chuanbin; Yip, Ashley; Gibson, Deanna L.

    2013-01-01

    Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses

  5. Protein Arginine Methyltransferase 5 Inhibition Upregulates Foxp3+ Regulatory T Cells Frequency and Function during the Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Yingxia Zheng

    2017-05-01

    Full Text Available Ulcerative colitis (UC pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3+ regulatory T cells (Tregs plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms. In this study, we found that protein arginine N-methyltransferase inhibitor 1 (AMI-1 treatments increased Tregs frequency, function, and reduced colitis incidence. Adoptive transfer of AMI-1-treated Tregs could reduce the colitis incidence. Colitis was associated with increased local PRMT5 expression, which was inhibited by AMI-1 treatment. Additionally, PRMT5 knockdown T cells produced a better response to TGFβ and promoted Tregs differentiation through decreased DNA methyltransferase 1 (DNMT1 expression. PRMT5 also enhanced H3K27me3 and DNMT1 binding to Foxp3 promoter, which restricted Tregs differentiation. Furthermore, PRMT5 knockdown led to decreased Foxp3 promoter methylation during Tregs induction. PRMT5 expression had a negative relationship with Tregs in UC patients, knockdown of PRMT5 expression increased Tregs frequency and decreased TNFα, IL-6, and IL-13 levels. Our study outlines a novel regulation of PRMT5 on Tregs development and function. Strategies to decrease PRMT5 expression might have therapeutic potential to control UC.

  6. The Demographic and Clinical Characteristics of Ulcerative Colitis in a Northeast Brazilian Population

    Directory of Open Access Journals (Sweden)

    Bruno César da Silva

    2015-01-01

    Full Text Available Introduction. The purpose of this study was to describe the clinical and demographic characteristics of UC in Bahia, a Brazilian state, and to identify the variables associated with extensive colitis, steroid therapy, immunosuppression, and colectomy. Methods. In this cross-sectional study UC patients were interviewed, and additional information was collected from the medical records. Descriptive statistics and multivariate Poisson regression analysis were used. Results. This study included 267 individuals, the mean age of whom was 39.4 years at diagnosis. There was a predominance of females and left-side colitis. Extensive colitis was positively associated with male gender, diarrhea, weight loss, and a younger age at diagnosis. In contrast, active smoking and a family history of IBD were negatively associated with extensive colitis. Positive associations were observed between steroid therapy and diarrhea, weight loss, urban patients, extraintestinal manifestations (EIMs, and hospitalization. Younger age and weight loss at diagnosis, a family history of IBD, extensive colitis, EIMs, hospitalization, and steroid therapy were all positively associated with immunosuppression. In contrast, Caucasian individuals, smokers, patients with rectal bleeding, and rural patients areas were all observed to have a decreased likelihood of immunosuppression. Conclusions. Our results corroborate the association between higher prevalence of extensive colitis and younger age at diagnosis. An association between steroid therapy and clinical presentation at diagnosis was observed. The observation that white individuals and rural patients use less immunosuppressive drugs highlights the need to study the influence of environmental and genetic factors on the behavior of UC in this population.

  7. Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin.

    OpenAIRE

    Moayyedi, P; O'Mahony, S; Jackson, P; Lynch, D A; Dixon, M F; Axon, A T

    1997-01-01

    There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous...

  8. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  9. European Crohn's and Colitis Organisation Topical Review on Environmental Factors in IBD

    DEFF Research Database (Denmark)

    Maaser, Christian; Langholz, Ebbe; Gordon, Hannah

    2017-01-01

    This ECCO Topical Review of the European Crohn's and Colitis Organisation [ECCO] focuses on the role of environmental factors with respect to the development of inflammatory bowel disease [IBD] as well as their influence on the course of established IBD. The objective was to reach expert consensus...... to provide evidence-based guidance for clinical practice....

  10. Disseminated refractory pyoderma gangraenosum during an ulcerative colitis flare. Treatment with infliximab.

    Science.gov (United States)

    Zampeli, Vasiliki A; Lippert, Undine; Nikolakis, Georgios; Makrantonaki, Evgenia; Tzellos, Thrasivoulos G; Krause, Ulf; Zouboulis, Christos C

    2015-09-30

    Pyoderma gangraenosum is an immune-mediated, inflammatory, neutrophilic dermatosis of unknown etiology, which represents one of the extraintestinal manifestations of inflammatory bowel disease. It is a rare disease that occurs in less than 1% of patients with inflammatory bowel disease and with the same ratio in patients with Crohn's disease and ulcerative colitis. A 36-year-old woman was diagnosed with ulcerative colitis 6 years before admission to our dermatology department with an acute disseminated pyoderma gangraenosum with mucosal involvement, during a flare of ulcerative colitis. Disease progression was interrupted by intravenous administration of the tumor necrosis factor-α inhibitor infliximab at 5 mg/kg at weeks 0, 2, and 6 (1st cycle) and every 8 weeks thereafter. Improvement of intestinal, skin and oral manifestations was evident already after the 1st cycle of treatment and has been maintained since (at least 16 months). This case report is one of very few on disseminated pyoderma gangraenosum with oral involvement complicating ulcerative colitis, where infliximab was shown to have a rapid efficacy on skin, mucosal and bowel symptoms.

  11. Hypokalemia-associated catastrophic rhabdomyolysis in ulcerative colitis

    International Nuclear Information System (INIS)

    Tzvetanov, G.

    2009-01-01

    A case of catastrophic hypokalemia-associated rhabdomyolysis in patient with ulcerative colitis (UC) is reported. A 60-year-old man presented with an exacerbation of UC and hypokalemia due to long-term diarrhea. While in the hospital, rhabdomyolysis developed in association with worsening hypokalemia. The hypokalemia was refractory to treatment and progressive course. Patient developed painful cramps of the masticatory and facial musculature associated with a moderated weakness in distal muscle groups. The weakness extended to intercostals and diaphragm muscles and led to respiratory deficiency. Serum concentration of creatine kinase was highly increased. Patient died from advancing and insurmountable cardiovascular deficiency. The causative role of hypokalemia for muscle involvement and rhabdomyolysis in patients with inflammatory bowel diseases was discussed. (author)

  12. Development of a quality instrument for assessing the spontaneous reports of ADR/ADE using Delphi method in China.

    Science.gov (United States)

    Chen, Lixun; Jiang, Ling; Shen, Aizong; Wei, Wei

    2016-09-01

    The frequently low quality of submitted spontaneous reports is of an increasing concern; to our knowledge, no validated instrument exists for assessing case reports' quality comprehensively enough. This work was conducted to develop such a quality instrument for assessing the spontaneous reports of adverse drug reaction (ADR)/adverse drug event (ADE) in China. Initial evaluation indicators were generated using systematic and literature data analysis. Final indicators and their weights were identified using Delphi method. The final quality instrument was developed by adopting the synthetic scoring method. A consensus was reached after four rounds of Delphi survey. The developed quality instrument consisted of 6 first-rank indicators, 18 second-rank indicators, and 115 third-rank indicators, and each rank indicator has been weighted. It evaluates the quality of spontaneous reports of ADR/ADE comprehensively and quantitatively on six parameters: authenticity, duplication, regulatory, completeness, vigilance level, and reporting time frame. The developed instrument was tested with good reliability and validity, which can be used to comprehensively and quantitatively assess the submitted spontaneous reports of ADR/ADE in China.

  13. Efficacy of Adalimumab as a long term maintenance therapy in ulcerative colitis.

    LENUS (Irish Health Repository)

    McDermott, Edel

    2013-03-01

    Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF-alpha. There are limited data with regard to its efficacy in ulcerative colitis. We report experience of adalimumab in ulcerative colitis in a single centre with a focus on the ability of this agent to maintain response and avoid colectomy in the medium to long-term.

  14. Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis.

    Science.gov (United States)

    Stavely, Rhian; Robinson, Ainsley M; Miller, Sarah; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

    2015-12-30

    The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation. MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10(6) cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry. Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro. This study is the first

  15. Ischemic colitis or melanosis coli: a case report

    Directory of Open Access Journals (Sweden)

    Nadeem Mohammed

    2007-09-01

    Full Text Available Abstract Background Melanosis Coli is described as black or brown discolouration of the mucosa of the colon. Its a benign condition, which arises from anthraquinone laxative abuse and has no symptoms of its own. The main importance of diagnosing Melanosis Coli correctly lies in the fact that if its extensive, there may be difficulty in differentiating it from ischemic colitis. Case presentation We present a case of extensive Melanosis Coli involving the whole of large bowel that appeared gangrenous. A sub total colectomy was performed on presumed diagnosis of ischemic bowel. Conclusion This report reminds the clinicians that extensive Melanosis Coli may mimic ischemic colitis and thus must be considered as a differential diagnosis.

  16. Ischemic colitis after mesotherapy combined with anti-obesity medications.

    Science.gov (United States)

    Kim, Jong Bin; Moon, Won; Park, Seun Ja; Park, Moo In; Kim, Kyu-Jong; Lee, Jae Nam; Kang, Seong Joo; Jang, Lee La; Chang, Hee Kyung

    2010-03-28

    Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors.

  17. Clinical evaluation of {sup 99m}Tc-HMPAO labeled leukocyte imaging in ulcerative colitis

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Yasuhiro; Aburano, Tamio; Takashio, Tetsuya; Shuke, Noriyuki; Ayabe, Tokiyoshi; Nomura, Masashi; Kohgo, Yutaka; Ishikawa, Yukio; Satoh, Junichi [Asahikawa Medical Coll., Hokkaido (Japan)

    1996-07-01

    Inflammatory imaging using {sup 99m}Tc-HMPAO-labeled mixed leukocytes was assessed for use in treating 11 cases diagnosed as ulcerative colitis: 10 cases with total colitis and 1 with left-sided colitis. They consisted of 8 patients with relapse-remitting type and 3 with chronic continuous type. Radionuclide abdominal images were obtained at 1 hr, 4 hr and 24 hr after intravenous injection of 200 MBq prepared {sup 99m}Tc leukocytes. Obvious colonic activity noted at 4 hr served as the basis for positive comparative criterion in the present study. The diagnostic efficacy of radionuclide imaging was compared with endoscopic findings (based on Matts` classification) and the clinical manifestations as reference. The sensitivity and specificity of this imaging were 83.3% and 85.7%, respectively, these values being consistent with endoscopic findings and clinical manifestations at sites of disease activity. All of positive images changed to negative after treatment by leukocyte apheresis or glucocorticoid. Based on these results, {sup 99m}Tc leukocyte imaging can be used to accurately evaluate severity and treatment response in ulcerative colitis. Leukocytes may be closely related to the pathogenesis of ulcerative colitis. (author)

  18. Altered Cyclosporine Absorption in a Patient with Ulcerative Colitis, Sclerosing Cholangitis and Pancreatic Insufficiency

    Directory of Open Access Journals (Sweden)

    Mark G Swain

    1991-01-01

    Full Text Available Pancreatic insufficiency leading to altered cyclosporine absorption is reported in a 37-year-old man with ulcerative colitis and sclerosing cholangitis. Asymptomatic chronic pancreatitis occurs frequently in patients with ulcerative colitis, and even more commonly when there is coexistent sclerosing cholangitis. However, pancreatic insufficiency has been documented in only one patient previously with ulcerative colitis and sclerosing cholangitis. Pancreatic function testing can help to identify the complex etiology of malabsorption in these patients and is recommended in patients when liver transplantation is contemplated, as pancreatic insufficiency may alter the absorption of cyclosporine.

  19. Navy and black bean supplementation attenuates colitis-associated inflammation and colonic epithelial damage.

    Science.gov (United States)

    Monk, Jennifer M; Wu, Wenqing; Hutchinson, Amber L; Pauls, Peter; Robinson, Lindsay E; Power, Krista A

    2018-02-27

    The enriched levels of nondigestible fermentable carbohydrates and phenolic compounds found in common beans can exert immunomodulatory effects within the colon that improve gut health and mitigate the severity of colitis-associated inflammatory pathology. Prior to acute colitis onset, C57Bl/6 mice were prefed isocaloric 20% cooked navy bean (NB) or black bean (BB) diets for 3 weeks and switched to control basal diet (BD) 24 h prior to colitis induction via 5-day exposure to dextran sodium sulfate (2% w/v in drinking water)+3 days of fresh water. The severity of the acute colitis phenotype was attenuated by bean prefeeding, evidenced by reduced colon tissue inflammatory transcription factor activation (NFκB, STAT3) and inflammatory mediator levels in the colon (IL-1β, IL-6, IL-18 and MCP-1) and serum (TNFα, IL-6, IL-1β, MCP-1) versus BD (P≤.05). Additionally, biomarkers of enhanced wound repair responses were increased by bean prefeeding including colon tissue protein levels of IL-22, IL-27 and activated (i.e., GTP-bound) Cdc42 and Rac1 versus BD (P≤.05). mRNA expressions of genes involved in normal colonic epithelial function and the promotion of epithelial barrier integrity, defense and/or restitution and wound closure including MUC1, RELMβ, IgA and REG3γ were all increased in NB and BB prefed mice versus BD (P≤.05). Collectively, bean supplementation prior to colitis induction (i.e., mimicking disease relapse) primes the colonic microenvironment to attenuate the severity of the colitis inflammatory phenotype and maintain aspects of epithelial barrier function. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease.

    Science.gov (United States)

    Chetty, R; Hafezi, S; Montgomery, E

    2009-05-01

    Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens. The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia. ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis. ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.

  1. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    Science.gov (United States)

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

  2. Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-gamma Activity

    DEFF Research Database (Denmark)

    Pedersen, G.; Brynskov, Jørn

    2010-01-01

    OBJECTIVES: Impaired epithelial expression of peroxisome proliferator-activated receptor-gamma (PPAR gamma) has been described in animal colitis models and briefly in patients with ulcerative colitis, but the functional significance in humans is not well defined. We examined PPAR gamma expression...

  3. Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

    OpenAIRE

    Gibson, P; Rosella, O; Nov, R; Young, G

    1995-01-01

    The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 h...

  4. The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

    Science.gov (United States)

    Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

    2017-05-01

    To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

  5. [A case of collagenous colitis with watery diarrhea due to lansoprazole use in an elderly woman].

    Science.gov (United States)

    Ota, Hidetaka; Honda, Masayuki; Yamaguchi, Yasuhiro; Akishita, Masahiro; Ouchi, Yasuyoshi

    2012-01-01

    We report a case of a 75-year-old woman with urgent watery diarrhea, occurring 5 to 8 times per day, which began after starting lansoprazole (30 mg/day) for erosive gastritis. Her chronic watery diarrhea persisted for over 2 years with mild weight loss. Colonoscopy was performed and biopsies showed collagenous colitis in her transverse colon. We therefore replaced lansoprazole with famotidine (20 mg/day). Within 3 days after the discontinuation of lansoprazole, her watery diarrhea resolved and she recovered, and reported normal feces. Increasing age and female gender are major risk factors for collagenous colitis. The differential diagnosis of collagenous colitis should include: 1) an appropriate clinical history, excluding other etiologies, 2) normal or near-normal endoscopic and/or radiographic findings, and 3) colonoscopic biopsy histopathologic findings consistent with collagenous colitis. The histopathologic findings of colonoscopic biopsy are important for diagnosis. However, because of the colonoscopic burden in elderly patients, we first recommend the discontinuation of medications suspected to cause collagenous colitis.

  6. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334 ameliorates murine colitis

    Directory of Open Access Journals (Sweden)

    Gupta R

    2014-01-01

    Full Text Available Ram Gupta,1 Anita R Chaudhary,2 Binita N Shah,1 Avinash V Jadhav,3 Shitalkumar P Zambad,1 Ramesh Chandra Gupta,4 Shailesh Deshpande,4 Vijay Chauthaiwale,4 Chaitanya Dutt4 1Department of Pharmacology, 2Cellular and Molecular Biology, 3Preclinical Safety Evaluation, 4Discovery, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gandhinagar, Gujarat, India Background and aim: Mucosal healing in inflammatory bowel disease (IBD can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods: The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results: TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion: Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor

  7. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  8. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-12-07

    To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

  9. Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review.

    Science.gov (United States)

    Kawalec, Paweł

    2016-04-01

    Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem.

  10. Review article: colitis-associated cancer -- time for new strategies.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    Colorectal cancer (CRC) remains a feared and potentially life-threatening complication of both ulcerative colitis and Crohn\\'s colitis. Currently, the main preventive strategy is a secondary one, i.e. surveillance colonoscopy usually after 8 years of disease duration, when the risk for neoplasia begins to increase. Despite its widespread acceptance, dysplasia and cancer surveillance is unproven in terms of reducing mortality or morbidity and there is a remarkable lack of uniformity in the manner in which it is practised. In this review article, the pitfalls of dysplasia surveillance are summarized and the need for novel chemopreventive and perhaps pharmabiotic approaches for prevention are highlighted.

  11. Non-IBD colitides: clinically useful histopathological clues Colitis no relacionadas con la enfermedad inflamatoria intestinal: claves histopatológicas de utilidad clínica

    Directory of Open Access Journals (Sweden)

    Vincenzo Villanacci

    2011-07-01

    Full Text Available Apart from inflammatory bowel diseases (IBD, there are several other form of colitis that may resemble macroscopically IBD, entering the differential diagnosis. These forms are represented by infectious colitis, ischemic colitis, pseudomembranous colitis, colitis related to diverticular disease, colitis related to mucosal prolapse, drug colitis, allergic colitis, and microscopic colitis. However, to distinguish between these forms is not always easy, and it frequently requires a strict interrelationship between the pathologist and the gastroenterologist. Here we discuss the more frequent forms of non- inflammatory bowel diseases colitides, trying to give useful hints for helping the clinician to better understand the extent to which the pathologist is called to give a definitive response in the differential diagnosis of these entities.

  12. Interstitial Lung Disease in a 70-Year-Old Man with Ulcerative Colitis.

    Science.gov (United States)

    Collins, Hampton W; Frye, Jeanetta W

    2018-01-01

    Interstitial lung disease is a rare but increasingly recognized extraintestinal manifestation of inflammatory bowel disease that can have devastating consequences if left untreated. We report a case of ulcerative colitis-associated interstitial lung disease presenting with acute hypoxic respiratory failure during an ulcerative colitis flare. Gastroenterologists and pulmonologists should be aware of the numerous bronchopulmonary signs and symptoms that can suggest systemic illness in inflammatory bowel disease.

  13. Hydrogen peroxide scavenger, catalase, alleviates ion transport dysfunction in murine colitis.

    Science.gov (United States)

    Barrett, Kim E; McCole, Declan F

    2016-11-01

    Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhoea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H 2 O 2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H 2 O 2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H 2 O. Mice were administered either pegylated catalase or saline at day -1, 0 and +1 of DSS treatment. Ion transport responses to the Ca 2+ -dependent agonist, carbachol (CCh), or the cAMP-dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS-induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS-induced reduction in baseline ion transport as well as colonic I sc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na + -K + -2Cl - cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhoea. © 2016 John Wiley & Sons Australia, Ltd.

  14. A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii.

    Science.gov (United States)

    Garrido-Mesa, José; Algieri, Francesca; Rodriguez-Nogales, Alba; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Zarzuelo, Antonio; Ocete, Maria Angeles; Garrido-Mesa, Natividad; Galvez, Julio

    2015-07-01

    Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses. Copyright © 2015 Elsevier Ltd. All

  15. Dasatinib-Induced T-Cell-Mediated Colitis: A Case Report and Review of the Literature.

    Science.gov (United States)

    Shanshal, Mohamed; Shakespeare, Andrew; Thirumala, Seshadri; Fenton, Boyd; Quick, Donald P

    2016-01-01

    Dasatinib is a potent inhibitor of the altered tyrosine kinase activity in disease states associated with BCR/ABL1. This agent has been shown to exhibit broad off-target kinase inhibition and immunomodulating properties. These effects may be responsible for dasatinib's unique side effects including a distinctive form of hemorrhagic colitis. We report a case of hemorrhagic colitis associated with dasatinib use in a patient with chronic myelogenous leukemia. Colon biopsies at the time of symptomatic colitis confirmed CD3+CD8+ T cell infiltration. The process rapidly resolved following drug discontinuation, but relapsed when rechallenged with a reduced dose of dasatinib. Colitis did not recur when the patient was treated with an alternative agent. A literature review of prior cases involving dasatinib-induced T-cell mediated colitis provides insight into commonalities that may facilitate the recognition and management of this entity. Most incidences occurred after a 3-month drug exposure and may be accompanied by large granular lymphocytes. The process uniformly resolves within a few days following drug discontinuation and will generally recur in a shorter period of time if the drug is reintroduced. Most patients will require an alternative agent, although select patients could be continued on dasatinib if other options are limited. © 2016 S. Karger AG, Basel.

  16. Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

    Directory of Open Access Journals (Sweden)

    Eva Pastille

    2017-09-01

    Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

  17. Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.

    Science.gov (United States)

    Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E

    2014-05-01

    Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

  18. Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3{sup +} regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Mitsui, Toshihito [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Sashinami, Hiroshi [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan); Sato, Fuyuki; Kijima, Hiroshi [Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Ishiguro, Yoh; Fukuda, Shinsaku [Department of Digestive Internal Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Yoshihara, Shuichi [Department of Glycomedicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Hakamada, Ken-Ichi [Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562 (Japan); Nakane, Akio, E-mail: a27k03n0@cc.hirosaki-u.ac.jp [Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562 (Japan)

    2010-11-12

    Research highlights: {yields} Salmon proteoglycan suppresses IL-10{sup -/-} cell transfer-induced colitis progression. {yields} Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. {yields} Salmon proteoglycan enhances Foxp3 expression. -- Abstract: Proteoglycans (PGs) are complex glycohydrates which are widely distributed in extracellular matrix (ECM). PGs are involved in the construction of ECM, cell proliferation and differentiation. ECM components are involved in transduction of proinflammatory responses, but it is still unknown whether PGs are involved in inflammatory response. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis-induced in severe combined immunodeficiency mice by cell transfer from interleukin-10 (IL-10){sup -/-} mice. IL-10{sup -/-} cell-transferred mice showed weight loss, colon shortening and histological appearance of mild colitis. Daily oral administration of PG attenuated the clinical progression of colitis in a dose-dependent manner. Colitis-induced mice showed the elevated expression of IFN-{gamma}, IL-12, TNF-{alpha}, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor {gamma}t (ROR{gamma}t) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4{sup +}CD25{sup +} regulatory T cells in LPMCs was enhanced by PG administration. These findings suggested that salmon PG attenuated the progression of colitis due to suppression of inflammatory response by enhancement of regulatory T cell induction.

  19. Ischemic colitis in five points: an update 2013.

    Science.gov (United States)

    Rania, Hefaiedh; Mériam, Sabbah; Rym, Ennaifer; Hyafa, Romdhane; Amine, Attaoui; Najet, Bel Hadj; Lassad, Gharbi; Mohamed, Taher Khalfallah

    2014-05-01

    Ischemic colitis is the most common form of intestinal ischemia. The presence of diarrhea and mild lower gastrointestinal bleeding should guide the diagnosis. Although many laboratory tests and radiographic images may suggest the diagnosis, colonic endoscopic with histological analysis of biopsies is the gold standard for identification of colonic ischemia. aim : The aim of this study was to resume in 5 points: the epidemiology, the clinical features, the diagnostic approach and the management of ischemic colitis in five points. methods: Review of literature. results: Incidence of ischemic colitis was between 3 and 10%. The clinical presentation is predominated by the non gangrenous form associating abdominal pain, tenderness, diarrhea and lower gastrointestinal bleeding. The most frequent causes are represented by systemic hypoperfusion. Laboratory tests can orientate the diagnosis but are unspecific. Radiographic images based on computed tomography or more recently magnetic resonance imaging may suggest the diagnosis, but the confirmation will be given by endoscopic visualization of colonic mucosa with histological analysis of biopsies. Conservative treatment is the most often sufficient to improve colonic lesions. Surgical treatment is reserved for perforations and strictures. The incidence of colonic ischemia is difficult to ascertain. The diagnosis is usually made by medical history, examination, and endoscopy which have become the diagnostic procedure of choice. A high index of suspicion and prompt management are essential for optimum outcomes in patients with colonic ischemia.

  20. Methotrexate in the treatment of peripheral arthritis in ulcerative colitis

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    R. Scarpa

    2011-06-01

    Full Text Available Objective: To evaluate efficacy of methotrexate treatment in peripheral arthritis of ulcerative colitis. Methods: We studied 18 patients (10/8 M/F; mean age: 38.90 yrs; range: 21-65 yrs, with peripheral arthritis (14 with polyarticular, 4 with oligoarticular subset associate ulcerative colitis. Methotrexate 20 mg/week was administered in our patients, who were already receiving mesalazina for inflammatory bowel disease. At baseline, after 3 (T1, 6 (T2 and 12 months (T3 serological parameters (ESR and CRP, functional status (HAQ and disease activity (VAS, GH, Ritchie articular index were evaluated. Results: During the therapy a significant improvement was observed in disease activity, functional status and serological parameters since T1. ESR and CRP did not change at T2 and T3. Instead VAS, GH, Ritchie articular index and HAQ had a significant and gradual improvement from T1 to T3. Conclusion: Methotrexate treatment was efficacious in the treatment of peripheral arthritis associate ulcerative colitis. This drug induced improvement in disease activity, functional status and serological parameters after 3 months of therapy.

  1. Selenoprotein P in colitis-associated carcinoma

    Science.gov (United States)

    Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

    2016-01-01

    ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

  2. Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

    Science.gov (United States)

    Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

    2015-05-27

    Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

  3. Pulmonary thromboembolism in a patient with active ulcerative colitis and lung abscess secondary to pulmonary infarction.

    Science.gov (United States)

    Asker, Selvi; Gunbatar, Hulya; Ekin, Selami; Sertogullarindan, Bunyamin; Sunnetcioglu, Aysel

    2014-12-01

    Crohn's disease and ulcerative colitis are inflammatory bowel diseases and they primarily involve intestines. Herein we report the case of a young man who, during a clinical recurrence of ulcerative colitis, presented with symptoms suggestive of a lung abscess. When the patient was re-evaluated because of unexplained shortness of breath, an area of infarction was detected that had led to the development of cavitation secondary to submassive embolism and foci of infection contained within. The patient was managed with subcutaneous heparin and he was asymptomatic during 2 months of follow-up. He completed six months of anti-coagulation therapy and any recurrence was not detected during 3 months of post-treatment follow-up.

  4. Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis.

    Directory of Open Access Journals (Sweden)

    Nicolette W Duijvis

    Full Text Available MicroRNAs (miRNAs are epigenetically involved in regulating gene expression. They may be of importance in the pathogenesis of inflammatory bowel disease (IBD. The aim of this study was to determine the role of miRNAs by their specific blocking in the CD4+CB45RBhi T-cell transfer model of chronic experimental colitis.Colitis caused by transfer of WT CD4+CD45RBhi T cells in severe combined immunodeficiency (SCID mice shares many features with human IBD. Colonic miRNA expression levels were measured at three time points in colitic mice, where a time-dependent upregulation of multiple miRNAs was seen. To inhibit these miRNAs, specific locked-nucleic-acid-modified (LNA oligonucleotides were administered in further experiments at the moment the mice demonstrated the first signs of colitis. As controls, PBS and a scrambled sequence of anti-miRNA were used. Genome-wide expression analyses were also performed in order to detect candidate target genes of miR-142-5p, of which inhibition resulted in most effective amelioration of colitis.Anti-miR-142-5p reduced colitis and related wasting disease when administered in the T-cell transfer model, reflected in reduced weight loss and a lower disease activity index (DAI. In further validation experiments we also observed a higher survival rate and less colonic histological inflammation in the antagomir-treated mice. Moreover, by genome-wide expression analyses, we found downstream activation of the anti-inflammatory IL10RA pathway, including three genes also found in the top-20 candidate target genes of miR-142-5p.In conclusion, CD4+CD45RBhi-transfer colitis induces miR-142-5p. Blocking miR-142-5p reduced colitis and prevented wasting disease, possibly by activation of the IL10RA pathway.

  5. Tracheitis – A Rare Extra-Intestinal Manifestation of Ulcerative Colitis in Children

    OpenAIRE

    Nunes, Isabel Serra; Abreu, Marlene; Corujeira, Susana; Oliveira, Juliana; Tavares, Marta; Rocha, Cristina; Lopes, Joanne; Carneiro, Fátima; Dias, Jorge Amil; Trindade, Eunice

    2016-01-01

    Introduction: Inflammatory bowel disease may cause both intestinal and extraintestinal manifestations. Respiratory symptoms in ulcerative colitis are rare and tracheal involvement is exceedingly rare in children. Case 1: Sixteen year-old female with a 4-week-complaint of abdominal pain, bloody diarrhea, fever and cough. The investigation was consistent with the diagnosis of concomitant ulcerative colitis/coinfection to Escherichia coli. On day 4 respiratory signs persisted so azithromycin ...

  6. Pseudomembranous colitis within radiotherapy field following concurrent chemoradiation therapy: a case report

    Directory of Open Access Journals (Sweden)

    Shen BJ

    2013-01-01

    Full Text Available Bing-Jie Shen,1 Shih-Chiang Lin,2 Pei-Wei Shueng,1,3 Yueh-Hung Chou,4 Li-Ming Tseng,5 Chen-Hsi Hsieh1,6,71Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan; 2Division of Oncology and Hematology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 3Department of Radiation Oncology, National Defense Medical Center, Taipei, Taiwan; 4Department of Anatomical Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan; 5Division of Colorectal Surgery, Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, TaiwanAbstract: Development of nonantibiotic-associated pseudomembranous colitis has been reported in patients receiving chemotherapy. Herein, we report a case of a 70-year-old man with diabetes mellitus and hypertension who received concurrent chemoradiation therapy after surgery for stage III pT3N1M0 rectal cancer. After completion of the therapy, the patient presented with a 2-week history of intermittent watery diarrhea (seven to nine times per day. However, the patient was afebrile and laboratory examination revealed no evidence of leukocytosis. Computed tomography disclosed inflammation of the sigmoid colon, infiltrative changes around the anastomotic site, and edematous changes straddling the serosal surface. Colonoscopic examination revealed multiple whitish patches within the radiation field, a finding suggestive of pseudomembranous colitis. No concomitant antibiotics were used during the period of concurrent chemoradiation therapy. Empirical oral metronidazole (500 mg every 8 hours was administrated for 2 weeks. At the end of this treatment, stool culture was negative for Clostridium difficile. Physicians should be aware of the potential for the development of

  7. Efficacy of Bifidobacterium breve NCC2950 against DSS-induced colitis is dependent on bacterial preparation and timing of administration.

    Science.gov (United States)

    Hayes, C L; Natividad, J M M; Jury, J; Martin, R; Langella, P; Verdu, E F

    2014-03-01

    Probiotics have been proposed as a therapy for inflammatory bowel disease, but variations in strains, formulations, and protocols used in clinical trials have hindered the creation of guidelines for their use. Thus, preclinical insight into the mechanisms of specific probiotic strains and mode of administration would be useful to guide future clinical trial design. In this study, live, heat inactivated (HI), and spent culture medium preparations of the probiotic Bifidobacterium breve NCC2950 were administered to specific pathogen free C57BL/6 mice before or during colitis, as well as before colitis reactivation. Five days of 3.5% dextran sulphate sodium in drinking water was used to induce colitis. Pretreatment with live B. breve reduced disease severity, myeloperoxidase activity, microscopic damage, cytokine production, interleukin (IL)-12/IL-10 ratio, and lymphocyte infiltration in the colon. B. breve did not attenuate on-going colitis. After acute colitis, disease symptoms were normalised sooner with live and HI B. breve treatment; however, reactivation of colitis was not prevented. These findings indicate that the efficacy of a probiotic to modulate intestinal inflammation is dependent on the formulation as well as state of inflammation when administered. Overall, live B. breve was most efficacious in preventing acute colitis. Live and HI B. breve also promoted recovery from diarrhoea and colon bleeding after a bout of acute colitis.

  8. Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ

    OpenAIRE

    Kong, Rui; Luo, Hui; Wang, Nan; Li, Jingjing; Xu, Shizan; Chen, Kan; Feng, Jiao; Wu, Liwei; Li, Sainan; Liu, Tong; Lu, Xiya; Xia, Yujing; Shi, Yanhong; Zhou, Yingqun; He, Weigang

    2018-01-01

    Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors-γ (PPAR-γ), Portulaca regulation of PPAR-γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and fou...

  9. Golimumab for the treatment of ulcerative colitis

    NARCIS (Netherlands)

    Löwenberg, Mark; de Boer, Nanne K. H.; Hoentjen, Frank

    2014-01-01

    The introduction of therapeutic antibodies against tumor necrosis factor (TNF) had a major impact on the treatment of ulcerative colitis (UC). Infliximab and adalimumab are powerful agents that are used for remission induction and maintenance therapy in UC and have an acceptable safety profile.

  10. Surgery for Crohn's Disease and Ulcerative Colitis

    Science.gov (United States)

    ... life improves because the pain, inflammation, and other symptoms of ulcerative colitis are gone. Prior to surgery, patients should speak ... loop of intestine or organ (bladder, vagina, or skin). Because they ... be necessary if its symptoms do not respond to medications. In some cases, ...

  11. Neutrophilic dermatoses in a patient with collagenous colitis

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    Didac Barco

    2010-01-01

    Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

  12. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    International Nuclear Information System (INIS)

    Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

    2009-01-01

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  13. Interleukin 1α-Deficient Mice Have an Altered Gut Microbiota Leading to Protection from Dextran Sodium Sulfate-Induced Colitis.

    Science.gov (United States)

    Nunberg, Moran; Werbner, Nir; Neuman, Hadar; Bersudsky, Marina; Braiman, Alex; Ben-Shoshan, Moshe; Ben Izhak, Meirav; Louzoun, Yoram; Apte, Ron N; Voronov, Elena; Koren, Omry

    2018-01-01

    Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1

  14. Tenosynovitis of the ankles as onset of sarcoidosis in a patient with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    F. Cozzi

    2011-09-01

    Full Text Available Arthritis and tenosynovitis are frequently reported as complications of inflammatory bowel diseases. About 10% of patients with ulcerative colitis presents articular inflammation, usually in the phases of activity of intestinal disease. Tenosynovitis is also a frequent complication of ulcerative colitis. We describe here a case of tenosynovitis of both ankles occurring in a patient affected by ulcerative colitis not in active phase. Chest X-ray and TC showed hilar lymphonode enlargement and transbronchial biopsy confirmed the diagnosis of sarcoidosis. In this disease tenosynovitis is very rare, unlike arthritis that is rather common. In conclusion we observed a case of ankle bilateral tenosynovitis as onset manifestation of sarcoidosis.

  15. Lycopene, Lutein and Zeaxanthin May Reduce Faecal Blood, Mucus and Pus but not Abdominal Pain in Individuals with Ulcerative Colitis.

    Science.gov (United States)

    Głąbska, Dominika; Guzek, Dominika; Zakrzewska, Paulina; Włodarek, Dariusz; Lech, Gustaw

    2016-09-30

    The main symptom of ulcerative colitis is diarrhoea, which is often accompanied by painful tenesmus and faecal blood and mucus. It sometimes co-occurs with abdominal pain, fever, feeling of fatigue, loss of appetite and weight loss. Some dietary factors have been indicated as important in the treatment of ulcerative colitis. The aim of the study was to analyse the association between retinoid intake (total vitamin A, retinol, β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) and ulcerative colitis symptoms (abdominal pain, faecal blood, faecal mucus, faecal pus) in individuals with ulcerative colitis in remission. Assessment of diet was based on self-reported data from each patient's dietary records taken over a period of three typical, random days (2 weekdays and 1 day of the weekend). A total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. One in every four individuals with ulcerative colitis in remission was characterised as having inadequate vitamin A intake. Higher lycopene, lutein and zeaxanthin intakes in individuals with ulcerative colitis in remission were associated with lower faecal blood, mucus and pus but not with lower incidence of abdominal pain. Higher carotene intake in individuals with ulcerative colitis in remission may contribute to higher incidence of faecal mucus. Optimising intake of specific retinoids may enhance disease control in individuals with ulcerative colitis. Prospective studies, including patient reported and objective outcomes, are required to confirm this.

  16. Golimumab for moderate to severe ulcerative colitis

    NARCIS (Netherlands)

    Strik, Anne S.; Berends, Sophie E.; Mathôt, Ron A.; D'Haens, Geert R.; Löwenberg, Mark

    2017-01-01

    Golimumab (GLM) is a subcutaneously administered human anti-tumor necrosis factor (TNF) agent that has been approved by the regulatory authorities for the treatment of moderate to severe ulcerative colitis (UC) in 2013. Areas covered: Maintained clinical remission rates up to 50% have been shown in

  17. Spontaneous Intracranial Hypotension without Orthostatic Headache

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    Tülay Kansu

    2009-03-01

    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  18. Pouchitis-Associated Iritis (Uveitis Following Total Proctocolectomy and Ileal Pouch-to-Anal Anastomosis in Ulcerative Colitis

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    Hugh James Freeman

    2001-01-01

    Full Text Available A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis. Although no ophthalmological manifestations were present before the staged surgical procedures, iritis developed after appearance of the pouchitis. Both conditions subsequently resolved with oral corticosteroids and metronidazole.

  19. Activation of NF-κB: bridging the gap between inflammation and cancer in colitis-mediated colon carcinogenesis.

    Science.gov (United States)

    Setia, Shruti; Nehru, Bimla; Sanyal, Sankar Nath

    2014-02-01

    Several studies have shown the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis, but how these drugs act in case of inflammation-augmented tumorigenesis is still not clear. The present study therefore designs an animal model of colitis-associated colon cancer where 3% Dextran sufate sodium (DSS) is used to develop ulcerative colitis and DMH treatment leads to colon carcinogenesis as early as in six weeks. Clinical symptoms for ulcerative colitis were studied using Disease Activity Index (DAI) while myeloperoxidase assay marked the neutrophil infiltration in DSS and DMH treated groups. The present results indicated the upregulation of the activity of inflammatory marker enzyme, cyclooxygenase-2 (cox-2) and pro-inflammatory cytokines such as TNF-α, IL-1β, IL-4 and IFN-γ with the treatment of DSS as well as DMH. The presence of cytokines in the inflammatory milieu might lead to the transformation of cytoplasmic inactive NF-κB (Nuclear Factor κB) to its active nuclear form, thereby leading to tumorigenesis. The administration of celecoxib along with DSS and DMH, revealed its chemopreventive efficacy in colitis as well as colon cancer. The effect of different doses of DMH on mouse colon was also investigated to obtain a minimum dose of DMH which can induce visible lesions in mice colons at a high incidence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

    Science.gov (United States)

    Zheng, Bin; van Bergenhenegouwen, Jeroen; Overbeek, Saskia; van de Kant, Hendrik J G; Garssen, Johan; Folkerts, Gert; Vos, Paul; Morgan, Mary E; Kraneveld, Aletta D

    2014-01-01

    While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus) and Bifidobacterium breve (B. breve) on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC), and in vivo, using murine dextran sodium sulfate (DSS) colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th) 17 and regulatory T cell (Treg) subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  1. Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

    Directory of Open Access Journals (Sweden)

    Bin Zheng

    Full Text Available While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus and Bifidobacterium breve (B. breve on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC, and in vivo, using murine dextran sodium sulfate (DSS colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th 17 and regulatory T cell (Treg subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.

  2. Imaging of intestinal lymphocyte homing by means of pinhole SPECT in a TNBS colitis mouse model

    International Nuclear Information System (INIS)

    Bennink, Roelof J.; Montfrans, Catherine van; Jonge, Wouter J. de; Bruin, Kora de; Deventer, Sander J. van; Velde, Anje A. te

    2004-01-01

    Background and aims: The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD. Methods: TNBS sensitized and non-sensitized murine total splenocytes were labeled in vitro with 111 In-oxine and injected into either control or TNBS colitis BALB/c mice. Biodistribution and specific radioactive uptake, representing transferred cells, were determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labeled cells. In addition, the severity of inflammation was. Results: Migration of 111 In labeled splenocytes to the colon increased in time and was maximal at 48h after administration. The highest specific radioactive uptake ratio in the colon after 48h was observed in mice with TNBS colitis that received TNBS sensitized lymphocytes. Histological scoring confirmed the presence of colitis in the TNBS treated groups. Conclusion: Homing of TNBS-sensitized lymphocytes can be assessed in vivo by means of dedicated animal pinhole SPECT. Generally, this technique enables serial measurement of specific cell trafficking with potential of in vivo evaluation of novel anti-inflammatory strategies in inflammatory bowel disease

  3. Analysis and Modeling of the Galvanic Skin Response Spontaneous Component in the context of Intelligent Biofeedback Systems Development

    Science.gov (United States)

    Unakafov, A.

    2009-01-01

    The paper presents an approach to galvanic skin response (GSR) spontaneous component analysis and modeling. In the study a classification of biofeedback training methods is given, importance of intelligent methods development is shown. The INTENS method, which is perspective for intellectualization, is presented. An important problem of biofeedback training method intellectualization - estimation of the GSR spontaneous component - is solved in the main part of the work. Its main characteristics are described; results of GSR spontaneous component modeling are shown. Results of small research of an optimum material for GSR probes are presented.

  4. [Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

    Science.gov (United States)

    Biros, E; Staffa, R

    2011-12-01

    Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the

  5. COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

    Directory of Open Access Journals (Sweden)

    José Wander BREGANÓ

    2014-09-01

    Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

  6. Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis

    Directory of Open Access Journals (Sweden)

    van Bodegraven Adriaan A

    2011-05-01

    Full Text Available Abstract Background Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG and azathioprine (AZA in a murine model of IBD. Methods We induced acute or chronic colitis in BALB/c mice by one or four cycles of 3% dextran sulphate sodium (DSS, respectively. Mice were treated by daily gavages of various dosages of 6-tioguanine, azathioprine, or by phosphate buffered saline (PBS starting the first day of DSS or after two cycles of DSS, respectively. We monitored the efficacy and toxicity by measuring the weight change and serum alanine aminotransferase (ALT activity and by disease severity and histology, at the end of the experiment. Moreover, we measured cytokine production after colon fragment cultivation by enzyme-linked immunoabsorbent assay and numbers of apoptotic cells in the spleen by flow cytometry. Results 6-TG is effective in the treatment of acute DSS-induced colitis in a dose-dependent manner and 40 μg of 6-TG is significantly more effective in the treatment of acute colitis than both AZA and PBS. This effect is accompanied by decrease of IL-6 and IFN-γ production in colon. We did not observe histological abnormalities in liver samples from control (PBS or 6-TG treated mice. However, liver samples from most mice treated with AZA showed mild, yet distinct signs of hepatotoxicity. In chronic colitis, all thiopurine derivatives improved colitis, 20 μg of 6-TG per dose was superior. High doses of 6-TG led to significant weight loss at the end of the therapy, but none of the thiopurine derivatives increased levels of serum ALT. Both thiopurine derivatives reduced the proportion of apoptotic T helper cells, but a high production of both IL-6 and TGF-β was observed only in colon of AZA-treated mice. Conclusions Use of 6-TG in the treatment

  7. Epstein-Barr-virus-associeret lymfom hos en patient med colitis ulcerosa i behandling med azathioprin

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Kiszka-Kanowitz, Marianne; Albrectsen, Jens Mørch

    2008-01-01

    A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV-associat......A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV......-associated large B-cell lymphoma was confirmed, he died from multiple organ failure. AZA and 6-mercaptopurine are associated with the development of EBV-positive lymphomas in organ-transplanted patients. This type of lymphoma is a rare complication in inflammatory bowel disease....

  8. [Aseptic cutaneous breast abscesses associated with ulcerative colitis].

    Science.gov (United States)

    Sallé de Chou, C; Ortonne, N; Hivelin, M; Wolkenstein, P; Chosidow, O; Valeyrie-Allanore, L

    2016-02-01

    Inflammatory bowel diseases are associated with a broad range of cutaneous lesions. Herein we report the first case of aseptic skin abscesses associated with ulcerative colitis. Since March 2008, a 40-year-old woman presented with bilateral mammary abscesses, relapsing despite repeated antibiotic treatment. She was followed for ulcerative colitis diagnosed in 2011 by means of a rectal biopsy. Despite four surgical procedures, there was no improvement in her mammary abscesses and bilateral mastectomy was then proposed because of the persistent symptoms. Her general state of health remained stable. Clinically, there were bilateral inflammatory nodes with fistulae and pus. These lesions were extremely painful. Mild inflammatory syndrome was noted, but the immunological tests revealed nothing of note. Bacteriological, parasitological and mycological tests on biopsy specimens were negative. Histological examination of a surgical biopsy revealed lymphoplasmacytic infiltration of the dermis and subcutis with altered polymorphonuclear cells and epithelioid granuloma. The CT-scan showed no other remote lesions. The final diagnosis was cutaneous aseptic abscess syndrome associated with ulcerative colitis. Colchicine 1mg/day was initiated and resulted in regression of the skin lesions, with complete remission at one year of follow-up. Aseptic abscess syndrome must be considered in the event of recurrent aseptic cutaneous abscesses which may be associated with inflammatory bowel disease. Surgery should be avoided and treatment should be based on suitable drug therapy. Copyright © 2016. Published by Elsevier Masson SAS.

  9. Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis Infliximab induce respuesta clínica, endoscópica e histológica en la colitis ulcerosa refractaria

    Directory of Open Access Journals (Sweden)

    F. Bermejo

    2004-02-01

    Full Text Available Background: infliximab is a monoclonal antiTNF-α antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. Aim: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. Patients and methods: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein, endoscopic, and histological changes were also assessed. Results: mean age of patients was 45.8 ± 17 years (range 23-77; 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99% both from a clinical (p = 0.01 and biochemical (p Introducción: infliximab, un anticuerpo monoclonal quimérico antiTNF-α ha demostrado su eficacia en pacientes con enfermedad de Crohn. Sin embargo, son escasos los datos sobre su efectividad en el tratamiento de la colitis ulcerosa. Objetivo: describir la experiencia conjunta de 3 hospitales españoles en el uso de infliximab en enfermos con CU activa resistente a otros tratamientos. Pacientes y métodos: se presentan 7 casos de colitis ulcerosa (6 con enfermedad crónicamente activa a pesar de tratamiento con inmunosupresor y 1 con colitis aguda grave refractaria a esteroides tratados con infliximab a dosis de 5 mg/kg de peso. Se evaluó la respuesta clínica mediante un Índice de Actividad Clínica trascurridas 2, 4 y 8 semanas de la infusión inicial. Así mismo, se estudiaron los cambios analíticos (velocidad de sedimentación y proteína C reactiva, endoscópicos e histol

  10. The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.

    Science.gov (United States)

    Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y

    2014-09-01

    Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

  11. Lycopene, Lutein and Zeaxanthin May Reduce Faecal Blood, Mucus and Pus but not Abdominal Pain in Individuals with Ulcerative Colitis

    Science.gov (United States)

    Głąbska, Dominika; Guzek, Dominika; Zakrzewska, Paulina; Włodarek, Dariusz; Lech, Gustaw

    2016-01-01

    Background: The main symptom of ulcerative colitis is diarrhoea, which is often accompanied by painful tenesmus and faecal blood and mucus. It sometimes co-occurs with abdominal pain, fever, feeling of fatigue, loss of appetite and weight loss. Some dietary factors have been indicated as important in the treatment of ulcerative colitis. The aim of the study was to analyse the association between retinoid intake (total vitamin A, retinol, β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) and ulcerative colitis symptoms (abdominal pain, faecal blood, faecal mucus, faecal pus) in individuals with ulcerative colitis in remission. Methods: Assessment of diet was based on self-reported data from each patient’s dietary records taken over a period of three typical, random days (2 weekdays and 1 day of the weekend). Results: A total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. One in every four individuals with ulcerative colitis in remission was characterised as having inadequate vitamin A intake. Higher lycopene, lutein and zeaxanthin intakes in individuals with ulcerative colitis in remission were associated with lower faecal blood, mucus and pus but not with lower incidence of abdominal pain. Higher carotene intake in individuals with ulcerative colitis in remission may contribute to higher incidence of faecal mucus. Conclusions: Optimising intake of specific retinoids may enhance disease control in individuals with ulcerative colitis. Prospective studies, including patient reported and objective outcomes, are required to confirm this. PMID:27706028

  12. Protective Effect of Daikenchuto on Dextran Sulfate Sodium-Induced Colitis in Mice

    OpenAIRE

    Matsunaga, Takaharu; Hashimoto, Shinichi; Yamamoto, Naoki; Kawasato, Ryo; Shirasawa, Tomohiro; Goto, Atsushi; Fujisawa, Koichi; Takami, Taro; Okamoto, Takeshi; Nishikawa, Jun; Sakaida, Isao

    2017-01-01

    Aim. To investigate the effect of daikenchuto (TJ-100; DKT) for ulcerative colitis (UC) model mouse and assess its anti-inflammatory mechanisms. Methods. We evaluated the effects of DKT on dextran sulfate sodium- (DSS-) induced experimental colitis. First, we assessed the short-term effects of DKT using two groups: 5% DSS group and 5% DSS with DKT group. Colon length; histological scores; and interleukin- (IL-) 10, IL-1?, and tumor necrosis factor-? mRNA expression profiles were analyzed usin...

  13. Biomarkers and Microscopic Colitis: An Unmet Need in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Laura Francesca Pisani

    2017-05-01

    Full Text Available One of the most common causes of chronic diarrhea is ascribed to microscopic colitis (MC. MC is classified in subtypes: collagenous colitis (CC and lymphocytic colitis (LC. Patients with MC report watery, non-bloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient’s health-related quality of life. A greater awareness, and concomitantly an increasing number of diagnoses over the last years, has demonstrated that the incidence and prevalence of MC are on the rise. To date, colonoscopy with histological analysis on multiple biopsies collected along the colon represents the unique accepted procedure used to assess the diagnosis of active MC and to evaluate the response to medical therapy. Therefore, the emerging need for less-invasive procedures that are also rapid, convenient, standardized, and reproducible, has encouraged scientists to turn their attention to the identification of inflammatory markers and other molecules in blood or feces and within the colonic tissue that can confirm a MC diagnosis. This review gives an update on the biomarkers that are potentially available for the identification of inflammatory activity, related to CC and LC.

  14. The Hydrogen Peroxide Scavenger, Catalase, Alleviates Ion Transport Dysfunction in Murine Colitis

    Science.gov (United States)

    Barrett, Kim E.; McCole, Declan F.

    2016-01-01

    Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H2O2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H2O2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H2O. Mice were administered either pegylated-catalase or saline at day −1, 0 and +1 of DSS treatment. Ion transport responses to the Ca2+-dependent agonist, carbachol (CCh), or the cAMP-dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS-induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS-induced reduction in baseline ion transport as well as colonic Isc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na+-K+-2Cl− cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhea. PMID:27543846

  15. Microscopic colitis - a missed diagnosis in diarrhea-predominant irritable bowel syndrome.

    Science.gov (United States)

    Stoicescu, Adriana; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Cristian; Diculescu, Mircea

    2012-01-01

    Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper

  16. Chemical colitis due to peracetic acid: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Angelo Zullo

    2011-01-01

    Full Text Available Reprocessing of both endoscopic instruments and reusable disposals is mandatory to prevent infection transmission. However, toxic colitis due to endoscope contamination by different disinfectants following an imperfect washing has been reported. We present a case of peracetic acid-induced colitis and reviewed the literature. Overall, five cases of peracetic acid toxic colitis have been reported. All cases presented with "snow white sign" immediately appearing during endoscopy, two patients complaint of mild abdominal pain (one of whom had also fever and rectal bleeding, whilst the others remained totally asymptomatic. Only one patient received a 1-week metronidazole treatment. No immediate complications were observed, and no sequels occurred at clinical-endoscopic follow-up. The identified cause of disinfectant contamination was a defective either manual or automated rinsing of the colonoscope following the reprocessing procedure.

  17. Positive correlation between disease activity index and matrix metalloproteinases activity in a rat model of colitis.

    Science.gov (United States)

    Oliveira, Luiz Gustavo de; Cunha, André Luiz da; Duarte, Amaury Caiafa; Castañon, Maria Christina Marques Nogueira; Chebli, Júlio Maria Fonseca; Aguiar, Jair Adriano Kopke de

    2014-01-01

    Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (Pcorrelation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

  18. Microarray Assisted Gene Discovery in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    Inflammatory Bowel disease (IBD) is a condition characterised by chronic recidivous inflammation of the bowel and intestine. IBD includes chron´s disease (CD) and ulcerative colitis (UC). The combined prevalence of CD and UC are app. 1 in 500 in the general Caucasian population. In 25% of the cas...

  19. TNF-a-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo

    2012-01-01

    was investigated in colonic biopsies of ulcerative colitis (UC) patients and in dextran sodium sulfate (DSS)-induced colitis. CDX2 protein expression was investigated by immunoblotting and immunohistochemical procedures. CDX2 and MEP1A regulation was examined in TNF-a-treated Caco-2 cells by reverse transcription...

  20. Development and Improvement of Simple Colonic Mucosal Ulcer during Treatment of Severe Ulcerative Colitis with Tacrolimus

    Directory of Open Access Journals (Sweden)

    Ayumi Ito

    2017-03-01

    Full Text Available Diarrhea, melena, and lower abdominal pain developed in a male in his 20s and colonoscopy showed pancolitis-type severe ulcerative colitis (UC. Treatment was initiated with 4,000 mg of 5-aminosalicylic acid and 60 mg/day of prednisolone, but the symptoms and inflammatory reaction worsened with prednisolone dose reduction. Tacrolimus was added to the treatment, which subsequently induced remission. Serial colonoscopies during the treatment showed improvement in ulcer and mucosal edema throughout the entire large intestine, but a new solitary round ulcer appeared at the end of the ileum. Since no signs of Behçet’s disease were noted, it was considered as a simple ulcer, a complication of UC. Tacrolimus treatment was continued based on continued improvement in clinical features and colonic mucosa, excluding the end of the ileum. Colonoscopy at 6 months after initiation of tacrolimus showed healing of the large intestinal mucosa, although mild congestion was still noted. The solitary round ulcer at the end of the ileum improved to a small erosion. We report the improvement of a simple ulcer that developed during tacrolimus treatment.

  1. Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis.

    Science.gov (United States)

    Yao, Junlin; Xie, Jiansheng; Xie, Binbin; Li, Yiran; Jiang, Liming; Sui, Xinbing; Zhou, Xiaoyun; Pan, Hongming; Han, Weidong

    2016-09-01

    Chronic inflammation in the intestine is a strong risk factor for colitis-associated colorectal cancer (CAC). Hydroxychloroquine (HCQ) is widely used as an anti-inflammatory drug in the treatment of immune-mediated inflammatory disorders and various tumors. However, little is known regarding the effects of HCQ on colitis-associated tumorigenesis. In this study, mice treated with HCQ showed a significant reduction in early-stage colitis following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration, as well as a remarkable inhibition of colonic tumorigenesis and tumor growth at late stages of CAC. Mechanistically, the therapeutic effects of HCQ were attributed to inhibition of inflammatory responses and production of mutagenic reactive oxygen species (ROS) in immune cells and subsequent promotion of apoptosis and cell cycle arrest in tumor cells. Furthermore, we found that HCQ inhibited the production of inflammatory cytokines and ROS in response to toll-like receptor 4 (TLR4) activation in macrophages. Our data presented herein may help guide the clinical use of HCQ as a prevention and treatment strategy for CAC. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome

    Science.gov (United States)

    Ruiz, Pedro A; Morón, Belen; Becker, Helen M; Lang, Silvia; Atrott, Kirstin; Spalinger, Marianne R; Scharl, Michael; Wojtal, Kacper A; Fischbeck-Terhalle, Anne; Frey-Wagner, Isabelle; Hausmann, Martin; Kraemer, Thomas; Rogler, Gerhard

    2017-01-01

    Objective Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO2) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Design Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO2 nanoparticles. The proinflammatory effects of TiO2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Results Oral administration of TiO2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO2-administered mice. In vitro, TiO2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. Conclusion These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2 nanoparticles. PMID:26848183

  3. Effect of live Salmonella Ty21a in Dextran Sulfate Sodium-induced Colitis

    Directory of Open Access Journals (Sweden)

    Gunnar Nysœter

    2007-01-01

    Full Text Available Background Intestinal microbiota seems to play an essential role in the development of inflammatory bowel diseases (IBD. We hypothesised that an oral vaccine based on live Salmonella typhi would be well tolerated and could even attenuate dextran sulfate sodium (DSS induced colitis in rats, an animal model of IBD. Methods Nine male Wistar rats was used for an initial tolerance study, in which we used 3 dose-levels of Salmonella Ty21a, 0.5 × 10 9 , 1 × 10 9 , and 2 × 10 9 CFU, each dose being tested in 3 rats. Four treatment groups consisting of 8 male Wistar rats per group: 1 control group given standard food and water, 2 control group given four daily administrations of Salmonella Ty21a 1 × 10 9 CFU, 3 water with 5% DSS the last 7 days, 4 four daily administrations of Salmonella Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with the drinking water from day 15 to 22. The animals were sacrificed and colonic tissue removed for analysis 22 days after gavage of the first vaccine dose. Results The animals in the tolerance study got no signs of disease. In the treatment study, all animals receiving DSS had histologic indications of colitis, particularly in the distal part of the colon. Administration of Salmonella Ty21a had no significant effect on crypt and inflammation scores (p > 0.05. Conclusion Gastric administration of live vaccine strain Salmonella Ty21a was well tolerated, but did not provide any significant protection against development of DSS induced colitis in rats.

  4. Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome.

    Science.gov (United States)

    Ruiz, Pedro A; Morón, Belen; Becker, Helen M; Lang, Silvia; Atrott, Kirstin; Spalinger, Marianne R; Scharl, Michael; Wojtal, Kacper A; Fischbeck-Terhalle, Anne; Frey-Wagner, Isabelle; Hausmann, Martin; Kraemer, Thomas; Rogler, Gerhard

    2017-07-01

    Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO 2 ) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO 2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO 2 nanoparticles. The proinflammatory effects of TiO 2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO 2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Oral administration of TiO 2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO 2 -administered mice. In vitro, TiO 2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO 2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO 2 nanoparticles. 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/.

  5. Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Masashi Ohno

    Full Text Available Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin on experimental colitis in mice.BALB/c mice were fed with 3% dextran sulfate sodium (DSS in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR.Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa.Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

  6. Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

    Science.gov (United States)

    da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

    2017-06-01

    The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Using spontaneous commentary of nursing home residents to develop resident-centered measurement tools: A case study.

    Science.gov (United States)

    Bangerter, Lauren R; Abbott, Katherine; Heid, Allison; Eshraghi, Karen; Van Haitsma, Kimberly

    Nursing home (NH) residents routinely complete surveys that assess their health, well-being, preferences, and care needs. Such surveys reveal important information, however, are largely based on the concerns of providers as opposed to the concerns of residents. Thus, researchers must enhance efforts to ensure that these surveys are guided by the priorities, needs, and concerns of residents. We present a case study to demonstrate how spontaneous commentary of NH residents holds particular efficacy for ensuring that measurement tools are guided by the needs, concerns, and priorities of residents. Spontaneous comments from NH residents (N = 370) collected as part of a study developing the Preferences for Everyday Living Inventory for NH residents (PELI-NH) were used to refine the PELI-NH across key phases of measurement development. This work demonstrates how the spontaneous commentary of NH residents may contribute to the refinement of NH measurement tools, and allow researchers to base these tools on the needs and priorities of NH residents. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

    Science.gov (United States)

    Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

    2017-11-01

    Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Ischemic Colitis after Weight-Loss Medication

    Directory of Open Access Journals (Sweden)

    Dan Comay

    2003-01-01

    Full Text Available BACKGROUND: Previous weight-loss medications have received cautious support due to their association with pulmonary hypertension and valvular heart disease. However, newer drugs are increasingly being recommended as potentially safer and more efficacious. We report a case of ischemic colitis possibly linked to the use of a weight-loss drug, and review the literature to highlight an important latent consequence of these medications.

  10. Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis

    Directory of Open Access Journals (Sweden)

    J. D. van Bergeijk

    1998-01-01

    Full Text Available From several in vitro and in vivo studies involvement of som atostatin (SMS in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 μg daily or octreotide (3 μg daily subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin1 β (IL-1 β, IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

  11. The prevalence of inflammatory bowel diseases, microscopic colitis, and colorectal cancer in patients with irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Magdy El-Salhy

    2011-07-01

    Full Text Available The diagnosis of irritable bowel syndrome (IBS is symptom-based and experts have developed diagnostic criteria for IBS. Distinguishing inflammatory bowel diseases (IBD from IBS, especially with mild disease activity, can be difficult. Another concern is microscopic colitis (MC. MC and IBS have similar symptoms and a normal endoscopic appearance. Our study investigated the prevalence of patients with IBD, MC, and colorectal cancer among 968 patients that fulfill the Rome III criteria for IBS. Among these patients, four were found with IBD (0.4% and seven with MC (0.7%. Among the IBD patients, three suffered from Crohn’s disease, affecting the terminal ileum, and one with ulcerative rectosigmoiditis. Of the seven patients with MC, two had collagenous colitis and five had lymphocytic colitis. Two IBS diarrhea-predominant patients had adenocarcin­oma in the sigmoid colon. These patients were a female aged 58 years and a male aged 56 years. We concluded from our study and earl­ier studies that symptom-based diagnosis of IBS may lead to missing a number of other gastrointestinal disorders that require quite different management than that for IBS.

  12. Sulphomucin expression in ileal pouches: emerging differences between ulcerative colitis and familial adenomatous polyposis pouches.

    LENUS (Irish Health Repository)

    Bambury, Niamh

    2012-02-03

    PURPOSE: We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. METHODS: Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. RESULTS: High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 +\\/- 0.5 vs. 0.556 +\\/- 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. CONCLUSIONS: Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation.

  13. Pulmonary Function in Ulcerative Colitis

    OpenAIRE

    A.H. Faghihi-Kashani; A. Kabir; S.A. Javad-Moosavi

    2008-01-01

    Background:Pulmonary involvement in ulcerative colitis (UC) is thought to be rare. There is not a definite document about the question that "Is the lung a target organ in inflammatory bowel disease?"The aim of the present study is to compare lung function between cases with UC and healthy controls. This study will also be of interest about searching the outbreak of pulmonary function abnormalities in a sample of Iranian patients with UC and factors associated with severity of UC. Me...

  14. Crohn's Disease and Ulcerative Colitis: A Guide for Parents

    Science.gov (United States)

    ... can control the chronic inflammation that is a hallmark of IBD. This will help achieve long-term ... by scar tissue perforation of the intestines colorectal cancer or risk of it In ulcerative colitis, the ...

  15. Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.

    Science.gov (United States)

    Zhou, Zijuan; Wang, Liang; Feng, Panpan; Yin, Lianhong; Wang, Chen; Zhi, Shengxu; Dong, Jianyi; Wang, Jingyu; Lin, Yuan; Chen, Dapeng; Xiong, Yongjian; Peng, Jinyong

    2017-01-01

    Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and western blotting. The effect of PFB on colitis was evaluated by examining the inflammatory response and intestinal epithelial barrier function. Our results showed that both TNFR1 and TNFR2 expression were significantly increased in a colitis model, and the increase was significantly reversed by PFB. Colitis symptoms, including infiltration of inflammatory cells, cytokine profiles, epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were significantly ameliorated by PFB. Compared with fruit bromelain and stem bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that exhibited on TNFR1. These results indicate that PFB showed a stronger selective inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit bromelain increases its selectivity on TNFR2 inhibition. High expression of epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB-induced TNFR inhibition ameliorated colitis symptoms. These results supply novel insights into potential IBD treatment by PFB.

  16. Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

    Science.gov (United States)

    Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

    2016-01-01

    Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

  17. The Development of Spontaneous Gender Stereotyping in Childhood: Relations to Stereotype Knowledge and Stereotype Flexibility

    Science.gov (United States)

    Banse, Rainer; Gawronski, Bertram; Rebetez, Christine; Gutt, Helene; Morton, J. Bruce

    2010-01-01

    The development of spontaneous gender stereotyping in children was investigated using the newly developed Action Interference Paradigm (AIP). This task consists of assigning gender-stereotypical toys as quickly as possible to boys and girls in either a stereotype-congruent or a stereotype-incongruent manner. A pilot study with 38 children (mean…

  18. Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

    Directory of Open Access Journals (Sweden)

    Piyush eJain

    2015-07-01

    Full Text Available Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS and repeated water avoidance stress (WAS on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC evoked aversive behavior (freezing, reduction of locomotion and exploration in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain.

  19. Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.).

    Science.gov (United States)

    Abd Alla, Mohamed D; Wolf, Roman; White, Gary L; Kosanke, Stanley D; Cary, David; Verweij, Jaco J; Zhang, Mie-Jie; Ravdin, Jonathan I

    2012-04-26

    To determine the efficacy of a Gal-lectin based intranasal synthetic peptide vaccine, we developed a new experimental primate model of Entamoeba histolytica intestinal infection. Release of xenic E. histolytica trophozoites (5×10(6)) into the small bowel of baboons (Papio sp.) resulted in a rapid intestinal anti-amebic antibody response and a brief infection; however, release of trophozoites directly into the cecum (5 baboons) elicited a sustained E. histolytica infection, as determined by quantitative fecal PCR, and an ulcerative, inflammatory colitis observed on colonoscopy and histopathology. In three controlled experiments, baboons received four immunizations at seven day intervals of 1600 μg of the vaccine/nostril, with Cholera toxin, 20 μg/nostril as adjuvant; vaccinated (n=6) and control baboons (n=6) baboons were then challenged via colonoscopy with xenic trophozoites (5×10(6)). During 90 days of follow up, 250 of 415 (60.24%) fecal samples in control baboons had a (+) PCR for E. histolytica, compared to only 36 of 423 (8.51%) samples from vaccinated baboons (P<0.001). All 6 vaccinated baboons were free of infection by the 51st day after challenge, 5 of 6 controls positive had (+) fecal PCRs for up to 126 days post-challenge (P=0.019). Inflammatory colitis developed in 4 of 6 control baboons post-challenge, with invasive E. histolytica trophozoites present in 2 of the 4 on histopathology. There was no evidence of inflammatory colitis or parasite invasion in any of the vaccinated baboons; there was a strong inverse correlation between positive ELISA OD value indicating the presence of intestinal anti-peptide IgA antibodies and baboons having a positive fecal PCR CT value, P<0.001. In conclusion, we developed a novel primate model of E. histolytica intestinal infection and demonstrated that a Gal-lectin-based intranasal synthetic peptide vaccine was highly efficacious in preventing experimental E. histolytica infection and colitis in baboons. Copyright

  20. Ulcerative Colitis in Colonic Interposition for Esophageal Atresia

    OpenAIRE

    Arshad, Hafiz Muhammad Sharjeel; Tetangco, Eula; Elkhatib, Imad

    2016-01-01

    A 38-year-old male with a history of colonic interposition for esophageal atresia as an infant presented with dysphagia and abdominal pain. On the basis of endoscopy findings, pathology, and response to therapy, he was found to have ulcerative colitis of the colonic conduit.

  1. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  2. The Potential Role of a Self-Management Intervention for Ulcerative Colitis: A Brief Report From the Ulcerative Colitis Hypnotherapy Trial

    Science.gov (United States)

    Keefer, Laurie; Kiebles, Jennifer L.; Kwiatek, Monika A.; Palsson, Olafur; Taft, Tiffany H.; Martinovich, Zoran; Barrett, Terrence A.

    2013-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory illnesses marked by unpredictable disease flares, which occur spontaneously and/or in response to external triggers, especially personal health behaviors. Behavioral triggers of flare may be responsive to disease self-management programs. We report on interim findings of a randomized controlled trial of gut-directed hypnotherapy (HYP, n = 19) versus active attention control (CON, n = 17) for quiescent ulcerative colitis (UC). To date, 43 participants have enrolled; after 5 discontinuations (1 in HYP) and 2 exclusions due to excessive missing data, 36 were included in this preliminary analysis. Aim 1 was to determine the feasibility and acceptability of HYP in UC. This was achieved, demonstrated by a reasonable recruitment rate at our outpatient tertiary care clinic (20%), high retention rate (88% total), and our representative IBD sample, which is reflected by an equal distribution of gender, an age range between 21 and 69, recruitment of ethnic minorities (~20%), and disease duration ranging from 1.5 to 35 years. Aim 2 was to estimate effect sizes on key clinical outcomes for use in future trials. Effect sizes (group × time at 20 weeks) were small to medium for IBD self-efficacy (.34), Inflammatory Bowel Disease Questionnaire (IBDQ) total score (.41), IBDQ bowel (.50), and systemic health (.48). Between-group effects were observed for the IBDQ bowel health subscale (HYP > CON; p = .05) at 20 weeks and the Short Form 12 Health Survey Version 2 (SF-12v2) physical component (HYP > CON; p < .05) at posttreatment and 20 weeks. This study supports future clinical trials testing gut-directed HYP as a relapse prevention tool for IBD. PMID:21362636

  3. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  4. 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

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    Li-Na Zhao

    Full Text Available BACKGROUND: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. METHODS: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI. Publication bias and heterogeneity were assessed. RESULTS: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84. Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. CONCLUSION: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

  5. Perspectives of IBD China: Is Crohn's and Colitis Foundation Model a Solution to Health Care Issues for the Country?

    Science.gov (United States)

    Chen, Yan

    2018-04-21

    The success of the Crohn's and Colitis Foundation of America (CCFA), now Crohn's and Colitis Foundation (CCF) has established a role model for developing countries with an increasing incidence of inflammatory bowel disease (IBD), including China. While there are shared etiopathogenetic pathways and clinical features in IBD between Eastern and Western countries, patients with IBD as well as health care professionals in China are facing distinctive challenges, including the fragmented and inconsistent health insurance, social support system, and three-tiered health care service. Financial burden remains to be a tremendous obstacle to the management of IBD. In addition, poor rapport between patients and clinicians, and the lack of properly trained IBD specialists makes a noticeable gap in the management of IBD between China and Western countries. The China Crohn's &Colitis Foundation (CCCF), closely following the successful model of CCF, was established under the same doctrine, and served as a non-profit, volunteer-driven organization dedicated to improving quality of life of patients in by IBD through education and training.

  6. Consenso mexicano para el diagnóstico y tratamiento de la colitis ulcerosa crónica idiopática

    Directory of Open Access Journals (Sweden)

    J.K. Yamamoto-Furusho

    2018-04-01

    Full Text Available Resumen: Estas guías constituyen una actualización de las guías publicadas en 2007. Desde ese año, los conocimientos acerca de la fisiopatología, así como las opciones terapéuticas, han evolucionado rápidamente, con la aprobación de nuevos agentes, la aparición de nuevos blancos terapéuticos y nuevas estrategias para mejorar los abordajes disponibles previamente.El objetivo de este consenso es promover una actualización y perspectiva mexicana sobre la epidemiología, el diagnóstico así como el tratamiento médico y quirúrgico de la colitis ulcerosa crónica idiopática.Los enunciados fueron finalmente votados y se realizaron las modificaciones finales en la junta de consenso. La evaluación de la evidencia por la clasificación GRADE se realizó al momento del consenso. Abstract: The guidelines presented herein are an updated version of the recommendations published in 2007. Since then, there has been a rapid advance in the knowledge about the pathophysiology of ulcerative colitis and its therapeutic options. New drugs have been approved, novel targeted therapies have emerged, and new strategies have been developed to improve the previously available approaches to the disease.The aim of the present consensus is to promote the current knowledge of and Mexican perspective on the epidemiology, diagnosis, and medical and surgical treatment of chronic idiopathic ulcerative colitis.The final vote on the statements and their ultimate modifications were carried out at the consensus working group meeting. Evidence was evaluated through the GRADE classification. Palabras clave: Colitis ulcerosa crónica idiopática, Diagnóstico, Tratamiento, Epidemiología, Colectomía, Pouchitis, Keywords: Ulcerative colitis, Diagnosis, Treatment, Epidemiology, Colectomy, Pouchitis

  7. Stability of Reference Genes for Messenger RNA Quantification by Real-Time PCR in Mouse Dextran Sodium Sulfate Experimental Colitis.

    Directory of Open Access Journals (Sweden)

    Nour Eissa

    Full Text Available Many animal models have been developed to characterize the complexity of colonic inflammation. In dextran sodium sulfate (DSS experimental colitis in mice the choice of reference genes is critical for accurate quantification of target genes using quantitative real time PCR (RT-qPCR. No studies have addressed the performance of reference genes in mice DSS-experimental colitis. This study aimed to determine the stability of reference genes expression (RGE in DSS-experimental murine colitis.Colitis was induced in male C57BL/6 mice using DSS5% for 5 days, control group received water. RNA was extracted from inflamed and non-inflamed colon. Using RT-qPCR, comparative analysis of 13 RGE was performed according to predefined criteria and relative colonic TNF-α and IL-1β gene expression was determined by calculating the difference in the threshold cycle.Colitis significantly altered the stability of mucosal RGE. Commonly used glyceraldehyde-3-phosphate dehydrogenase (Gapdh, β-actin (Actb, or β2-microglobulin (β2m showed the highest variability within the inflamed and control groups. Conversely, TATA-box-binding protein (Tbp and eukaryotic translation elongation factor 2 (Eef2 were not affected by inflammation and were the most stable genes. Normalization of colonic TNF-α and IL-1β mRNA levels was dependent on the reference gene used. Depending on the genes used to normalize the data, statistical significance varied from significant when TBP / Eef2 were used to non-significant when Gapdh, Actb or β2m were used.This study highlights the appropriate choice of RGE to ensure adequate normalization of RT-qPCR data when using this model. Suboptimal RGE may explain controversial results from published studies. We recommend using Tbp and Eef2 instead of Gapdh, Actb or β2m as reference genes.

  8. Successful Use of Adalimumab for Treating Pyoderma Gangrenosum with Ulcerative Colitis under Corticosteroid-tapering Conditions.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Nagai, Kenta; Hayashi, Ryohei; Chayama, Kazuaki

    2015-01-01

    A 52-year-old woman with ulcerative colitis was admitted to our hospital for an ulcerative colitis flare-up under salazosulfapyridine therapy. The symptoms improved with high-dose corticosteroids. After prednisolone was tapered to 10 mg, the frequency of diarrhea increased. The diarrhea was accompanied by joint pain and a skin ulcer with abscess formation, which was diagnosed to be pyoderma gangrenosum. The patient was started on adalimumab. A positive response to the adalimumab therapy was observed after 2 weeks, during which time the ulcerative skin lesion healed completely, however, colonic mucosal healing was achieved at 2 months. Therefore, adalimumab appears to be an effective therapeutic option for patients with ulcerative colitis-associated pyoderma gangrenosum.

  9. Clostridium difficile Infection Worsens the Prognosis of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    María E Negrón

    2014-01-01

    Full Text Available BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients.

  10. Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice.

    Science.gov (United States)

    Colombo, Bárbara B; Fattori, Victor; Guazelli, Carla F S; Zaninelli, Tiago H; Carvalho, Thacyana T; Ferraz, Camila R; Bussmann, Allan J C; Ruiz-Miyazawa, Kenji W; Baracat, Marcela M; Casagrande, Rúbia; Verri, Waldiceu A

    2018-04-10

    The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

  11. A case of obstructive colitis caused by rectal stenosis and adhesion due to irradiation

    International Nuclear Information System (INIS)

    Tochika, Naoshige; Sugimoto, Takeki; Takano, Atsushi; Kobayashi, Michiya; Matsuura, Kimio; Araki, Keijiro

    2000-01-01

    We report a case of obstructive colitis associated with rectal stenosis and adhesion due to irradiation. A 68-year-old woman who had been suffering from constipation after an episode of irradiation for cervical cancer of the uterus two years previously was admitted to our hospital complaining of the lower abdominal pain. After two days, an operation was performed under a diagnosis or panperitonitis. Stenosis and adhesion of the rectum and necrosis at the oral side of the adhesion was recognized. Histologically, necrosis of the rectum from mucosa to serosa was recognized, and no neoplastic change was seen at the stenotic portion. The most common cause of local stenosis of the colon leading to obstructive colitis is colon cancer. Obstructive colitis caused by a benign stenosis as reported here is rare. (author)

  12. A case of obstructive colitis caused by rectal stenosis and adhesion due to irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tochika, Naoshige; Sugimoto, Takeki; Takano, Atsushi; Kobayashi, Michiya; Matsuura, Kimio; Araki, Keijiro [Kochi Medical School, Nankoku (Japan)

    2000-03-01

    We report a case of obstructive colitis associated with rectal stenosis and adhesion due to irradiation. A 68-year-old woman who had been suffering from constipation after an episode of irradiation for cervical cancer of the uterus two years previously was admitted to our hospital complaining of the lower abdominal pain. After two days, an operation was performed under a diagnosis or panperitonitis. Stenosis and adhesion of the rectum and necrosis at the oral side of the adhesion was recognized. Histologically, necrosis of the rectum from mucosa to serosa was recognized, and no neoplastic change was seen at the stenotic portion. The most common cause of local stenosis of the colon leading to obstructive colitis is colon cancer. Obstructive colitis caused by a benign stenosis as reported here is rare. (author)

  13. Early manifestation of Yersinia colitis demonstrated by the double-contrast barium enema

    Energy Technology Data Exchange (ETDEWEB)

    Aspestrand, F.

    1986-11-01

    A 19-year old female with a bloody, diarrheal illness of acute onset where Crohn's disease primarly was suspected is presented. The double-contrast barium enema revealed multiple, diffusely scattered aphthous erosions of the colonic mucosa: the rectum was scarcely affected. Biopsies taken by endoscopy demonstrated nonspecific inflammatory changes of the mucous membrane. However, routinely taken stool cultures revealed an infectious colitis due to Yersinia enterocolitica. Our case demonstrates the necessity to consider Yersinia enterocolitis in the radiographic differential diagnosis when the diagnosis of Crohn's disease or ulcerative colitis seems obvious.

  14. Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis.

    Science.gov (United States)

    Lagishetty, Venu; Misharin, Alexander V; Liu, Nancy Q; Lisse, Thomas S; Chun, Rene F; Ouyang, Yi; McLachlan, Sandra M; Adams, John S; Hewison, Martin

    2010-06-01

    Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

  15. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  16. Chemokines involved in protection from colitis by CD4+CD25+ regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Brudzewsky, Dan; Gad, Monika

    2006-01-01

    /chemokine receptor-specific gene expression profiling system of 67 genes, the authors have determined the expression profile of chemokine and chemokine receptor genes in the rectum of colitic mice and in mice that have been protected fromcolitis by CD4CD25 regulatory T cells. In mice protected from colitis......, the authors found down regulation of the mRNA expression of the inflammatory chemokine receptors CCR1 and CXCR3 and their ligands CXCL9, CXCL10, CCL5, and CCL7. Also the transcripts for CCR9, CCL25, CCL17, and CXCL1 are found down regulated in protected compared with colitic animals. In addition, the authors......' results suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of controlling colitis because transcripts for this chemokine were expressed to a higher level in protected animals. The chemokine pathways identified in the present study may be of importance for the development of new...

  17. MTG16 contributes to colonic epithelial integrity in experimental colitis

    Science.gov (United States)

    Williams, Christopher S; Bradley, Amber M; Chaturvedi, Rupesh; Singh, Kshipra; Piazuelo, Maria B; Chen, Xi; McDonough, Elizabeth M; Schwartz, David A; Brown, Caroline T; Allaman, Margaret M; Coburn, Lori A; Horst, Sara N; Beaulieu, Dawn B; Choksi, Yash A; Washington, Mary Kay; Williams, Amanda D; Fisher, Melissa A; Zinkel, Sandra S; Peek, Richard M; Wilson, Keith T; Hiebert, Scott W

    2013-01-01

    Objective The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8−/− and Mtgr1−/− mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. Methods Baseline and stress induced colonic phenotypes were examined in Mtg16−/− mice. To unmask phenotypes, we treated Mtg16−/− mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. Results Mtg16−/− mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16−/− mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1+, F4/80+, CD11c+ and MHCII+; CD11c+) and Th1 adaptive (CD4) immune cells in Mtg16−/− colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16−/− colons. Compared with wild-type mice, Mtg16−/− mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wildtype marrow into Mtg16−/− recipients did not rescue the Mtg16−/− injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16−/− mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16−/− mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. Conclusions These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury. PMID:22833394

  18. miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops.

    Science.gov (United States)

    Wang, T; Xu, X; Xu, Q; Ren, J; Shen, S; Fan, C; Hou, Y

    2017-06-08

    Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3). miR-19a inhibition can also alleviate CAC in vivo. Moreover, the regulatory effects of miR-19a on TNFAIP3 and NF-κB signaling were confirmed using tumor samples from patients with colon cancer. These new findings demonstrate that miR-19a has a direct role in upregulating NF-κB signaling and that miR-19a has roles in inflammation and CAC.

  19. Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

    Science.gov (United States)

    Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

    2016-11-01

    This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Microscopic Colitis – A Missed Diagnosis in Diarrhea-Predominant Irritable Bowel Syndrome

    Science.gov (United States)

    STOICESCU, Adriana; BECHEANU, Gabriel; DUMBRAVA, Mona; GHEORGHE, Cristian; DICULESCU, Mircea

    2012-01-01

    ABSTRACT Background: Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. Aim: To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Material and methods: Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. Results: From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. Conclusions: All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost

  1. Developing spontaneity and well-being in women victims of domestic violence

    Directory of Open Access Journals (Sweden)

    Ines Testoni

    2015-01-01

    Full Text Available In this paper we present the results of the last stage of the research project Empower Daphne that involved the participation of six countries belonging to the EU in two phases: I validation of the theoretical model on which basis rests the construct of well-being and spontaneity; II analysis of Morenian psychodrama intervention efficacy. 407 university students were part of the non-clinical sample in the first phase and 136 women victims of domestic violence made up the clinical sample for the second phase. During the six month the women took part in psychodramatic sessions, together with individual interviews. At the beginning and the end of the six month, a questionnaire was administered consisting of a well-being and a spontaneity scales. In the article we present the results that compare well-being and spontaneity between clinical and non-clinical samples, and between the clinical cut-off scores highlighted in the literature and the scores of clinical sample. The findings demonstrate interesting differences between two sample: observed lower levels of spontaneity and well-being in women victims of domestic violence, both before and after the psychodramatic intervention.

  2. A Case of Pyoderma Gangrenosum with Ulcerative Colitis Treated with Mesalazine

    OpenAIRE

    Lee, Jae In; Park, Hyun Jeong; Lee, Jun Young; Cho, Baik Kee

    2010-01-01

    Pyoderma gangrenosum (PG) manifests as recurrent deep ulceration of the skin and PG is associated with a variety of disorders. Approximately 30% of the cases of PG develop in patients with inflammatory bowel disease. A 34-year-old woman presented with a one-week history of recurrent ulcers on the right cheek and back. She was diagnosed with ulcerative colitis (UC) 4 years previously and with PG 1 year previously. The clinical course of the skin lesions followed the status of her UC. The patie...

  3. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

    Directory of Open Access Journals (Sweden)

    Snezana Levic

    Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

  4. Cytotoxic reactivity of gut lamina propria CD4+ alpha beta T cells in SCID mice with colitis

    DEFF Research Database (Denmark)

    Bonhagen, K; Thoma, S; Bland, P

    1996-01-01

    Polyclonal, mucosa-seeking memory/effector CD4+ T cells containing a large fraction of blasts activated in situ accumulate in the gut lamina propria of severe-combined immunodeficient (SCID) mice developing colitis after CD4+ T cell transplantation. CD4+ T cells isolated from different repopulated...

  5. MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer.

    Science.gov (United States)

    Ma, Ning; Liu, Qilin; Hou, Lin; Wang, Yalin; Liu, Ziling

    2017-06-01

    Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation. Importantly, this MDSC accumulation was controlled by GM-CSF. MDSC number decreased significantly in GM-CSF-deficient mice suffering from CAC induction, and transfusion of MDSCs from wild-type CAC-bearing mice into GM-CSF-deficient counterparts led to recurrence of CAC. Furthermore, the supernatants of CAC lesions or GM-CSF alone was sufficient to differentiate hematopoietic precursors into MDSCs. Addition of neutralizing anti-GM-CSF antibody impaired the MDSC-differentiating effects of the supernatants of CAC lesions. Overall, these findings shed new insights into the mechanisms of GM-CSF underlying CAC development, by inducing/recruiting CAC-promoting MDSCs. Blocking GM-CSF activity or MDSC function may represent new therapeutic strategies for CAC in clinic.

  6. Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

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    Alexandra Wagnerova

    2017-01-01

    Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

  7. Medical Management of Ulcerative Colitis with a Specific Focus on 5-Aminosalicylates

    Directory of Open Access Journals (Sweden)

    Hugh James Freeman

    2012-01-01

    Full Text Available Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA, an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA—containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

  8. Medical management of ulcerative colitis with a specific focus on 5-aminosalicylates.

    Science.gov (United States)

    Freeman, Hugh James

    2012-01-01

    Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA), an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA-containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

  9. Diphtheroid colitis in a Boa constrictor infected with amphibian Entamoeba sp.

    Science.gov (United States)

    Richter, Barbara; Kübber-Heiss, Anna; Weissenböck, Herbert

    2008-05-06

    A female boa (Boa constrictor) from a zoological collection was submitted for necropsy after sudden death. Prominent pathological findings included a diphtheroid colitis, endoparasitism, focal pneumonia and inclusion bodies typical for inclusion body disease (IBD). In the colon entamoebae were identified, which differed in size and distribution from Entamoeba invadens. Gene sequence analysis of the 18S ribosomal RNA revealed 100% similarity with an Entamoeba species from the African bullfrog (Pyxicephalus adspersus), probably Entamoeba ranarum. The snake was possibly immunosuppressed, and the source of infection remains unclear. This is the first report of an infection with an amphibian Entamoeba species associated with colitis in a snake.

  10. Functional outcome and quality of life following restorative proctocolectomy for ulcerative colitis in Indians.

    Science.gov (United States)

    Somashekar, Uday; Gupta, Subash; Soin, Arvinder; Nundy, Samiran

    2010-08-01

    The functional outcome and quality of life after sphincter-saving operations for ulcerative colitis have not been previously assessed in Indian patients whose dietary habits and socio-cultural practices differ considerably from those in western countries. Between 1996 and 2002, we performed 46 J-pouch ileoanal anastomoses (IPAA), for patients with ulcerative colitis. Thirty-eight of these patients had had their ileostomy closure more than 4 years previously of whom 31 could be assessed by interviews and a telephonic questionnaire. Their quality of life was objectively assessed using the Cleveland Global Quality of Life (CGQL) index, a validated index for IPAA, the score being 1 in normal people. There were 20 males and 11 females with a mean age of 38 years. In the same period, six of the nine patients who did not opt to have an IPAA (permanent stoma) were assessed. These included four males and two females, mean age 45 years (36-52). One patient died in the postoperative period and another died 3 months after surgery from multiple small bowel perforations. Other complications included intestinal obstruction in seven, pouchitis in four and incisional hernia in two. One pouch had to be converted to a permanent ileostomy following development of a fistula because of Crohn's disease. The mean daily postoperative stool frequency was seven (range 2-20). Eighty-one percent had perfect daytime continence and 81% used dietary restrictions. Eighty-four percent rated their pouch function to be excellent or good. All patients preferred IPAA to an ileostomy citing mainly social and cultural reasons and were willing to choose it again. The mean preoperative CGQL score (0.27) increased significantly after colectomy (0.50) and after closure of ileostomy (0.77; p quality of life in Indians with ulcerative colitis and may be the most appropriate procedure for such patients in developing countries.

  11. A Limited Role of p53 on the Ability of a Hexane Fraction of American Ginseng to Suppress Mouse Colitis

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    Deepak Poudyal

    2012-01-01

    Full Text Available Ulcerative colitis (UC is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG, and to a greater extent, a Hexane fraction of AG (HAG can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo. Finally, we asked whether HAG could cause cell cycle arrest of HCT116 colon cancer cells in vitro. Interestingly, HAG caused a G1 arrest of such cells independent of p53 status. Findings are significant because HAG suppresses colitis and associated colon cancer, and mutation in p53 is observed in most colitis-driven colon cancers. Therefore, HAG might be very effective in targeting the inflammatory cells and cancer cells since it induces apoptosis of inflammatory cells and cell cycle arrest in both p53−/− and WT p53 colon cancer cells.

  12. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

  13. Consumption of Diet Containing Free Amino Acids Exacerbates Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Adna Luciana Souza

    2017-11-01

    Full Text Available Dietary proteins can influence the maturation of the immune system, particularly the gut-associated lymphoid tissue, when consumed from weaning to adulthood. Moreover, replacement of dietary proteins by amino acids at weaning has been shown to impair the generation of regulatory T cells in the gut as well as immune activities such as protective response to infection, induction of oral and nasal tolerance as well as allergic responses. Polymeric and elemental diets are used in the clinical practice, but the specific role of intact proteins and free amino acids during the intestinal inflammation are not known. It is plausible that these two dietary nitrogen sources would yield distinct immunological outcomes since proteins are recognized by the immune system as antigens and amino acids do not bind to antigen-recognition receptors but instead to intracellular receptors such as mammalian target of rapamycin (mTOR. In this study, our aim was to evaluate the effects of consumption of an amino acid-containing diet (AA diet versus a control protein-containing diet in adult mice at steady state and during colitis development. We showed that consumption of a AA diet by adult mature mice lead to various immunological changes including decrease in the production of serum IgG as well as increase in the levels of IL-6, IL-17A, TGF-β, and IL-10 in the small and large intestines. It also led to changes in the intestinal morphology, to increase in intestinal permeability, in the number of total and activated CD4+ T cells in the small intestine as well as in the frequency of proliferating cells in the colon. Moreover, consumption of AA diet during and prior to development of dextran sodium sulfate-induced colitis exacerbated gut inflammation. Administration of rapamycin during AA diet consumption prevented colitis exacerbation suggesting that mTOR activation was involved in the effects triggered by the AA diet. Therefore, our study suggests that different

  14. Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Kissow, Hannelouise; Hare, Kristine

    2005-01-01

    % dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg......2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score...... in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer....

  15. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  16. AOM/DSS Model of Colitis-Associated Cancer

    Science.gov (United States)

    Parang, Bobak; Barret, Caitlyn W.; Williams, Christopher S.

    2016-01-01

    Summary Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer. PMID:27246042

  17. AOM/DSS Model of Colitis-Associated Cancer.

    Science.gov (United States)

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.

  18. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    International Nuclear Information System (INIS)

    Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

    2015-01-01

    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 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 also 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

  19. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    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 also 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.

  20. Preventive and therapeutic effects of blueberry (Vaccinium corymbosum) extract against DSS-induced ulcerative colitis by regulation of antioxidant and inflammatory mediators.

    Science.gov (United States)

    Pervin, Mehnaz; Hasnat, Md Abul; Lim, Ji-Hong; Lee, Yoon-Mi; Kim, Eun Ok; Um, Byung-Hun; Lim, Beong Ou

    2016-02-01

    Inflammatory bowel disease (IBD) is an inflammatory disorder caused by hyperactivation of effector immune cells that produce high levels of proinflammatory cytokines. The aims of our study were to determine whether orally administered blueberry extract (BE) could attenuate or prevent the development of experimental colitis in mice and to elucidate the mechanism of action. Female Balb/C mice (n=7) were randomized into groups differing in treatment conditions (prevention and treatment) and dose of BE (50 mg/kg body weight). Acute ulcerative colitis was induced by oral administration of 3% dextran sodium sulfate for 7 days in drinking water. Colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. BE significantly decreased disease activity index and improved the macroscopic and histological score of colons when compared to the colitis group (P<.05). BE markedly attenuated myeloperoxidase accumulation (colitis group 54.97±2.78 nmol/mg, treatment group 30.78±1.33 nmol/mg) and malondialdehyde in colon and prostaglandin E2 level in serum while increasing the levels of superoxide dismutase and catalase (colitis group 11.94±1.16 U/ml, BE treatment group 16.49±0.39 U/ml) compared with the colitis group (P<.05). mRNA levels of the cyclooxygenase (COX)-2, interferon-γ, interleukin (IL)-1β and inducible nitric oxide synthase cytokines were determined by reverse transcriptase polymerase chain reaction. Immunohistochemical analysis showed that BE attenuates the expression of COX-2 and IL-1β in colonic tissue. Moreover, BE reduced the nuclear translocation of nuclear transcription factor kappa B (NF-κB) by immunofluorescence analysis. Thus, the anti-inflammatory effect of BE at colorectal sites is a result of a number of mechanisms: antioxidation, down-regulation of the expression of inflammatory mediators and inhibition of the nuclear translocation of NF-κB. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators.

    Science.gov (United States)

    Kannan, Narayanan; Guruvayoorappan, Chandrasekharan

    2013-05-01

    Inflammatory bowel diseases (IBD), including Crohn's disease and Ulcerative colitis (UC), are life-long and recurrent disorders of the gastrointestinal tract with unknown etiology. The present study is designed to evaluate the ameliorative effect of Bauhinia tomentosa during ulcerative colitis (UC). Three groups of animals (n=6) were treated with B. tomentosa (5, 10, 20 mg/kg B.wt respectively) for 5 consecutive days before induction of UC. UC was induced by intracolonic injection of 3% acetic acid. The colonic mucosal injury was assessed by macroscopic scoring and histological examination. Furthermore, the mucosal content of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide (NO), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity confirms that B. tomentosa could significantly inhibit colitis in a dose dependent manner. The myeloperoxidase (MPO), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS) expression studies and lactate dehydrogenase (LDH) assay also supported that B. tomentosa could significantly inhibit experimental colitis. The effect was comparable to the standard drug sulfasalazine. Colonic mucosal injury parallels with the result of histological and biochemical evaluations. The extracts obtained from B. tomentosa possess active substances, which exert marked protective effects in acute experimental colitis, possibly by regulating the antioxidant and inflammatory mediators. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Thomas Lindebo Holm

    2012-01-01

    Full Text Available Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs Crohn's disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase knowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates, that is, anti-TNF-α, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-α4β7 integrin, enrofloxacin/metronidazole, and cyclosporine. We found that anti-TNF-α, antibiotics, anti-IL-12p40, anti-α4β7 integrin, CTLA4-Ig, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies, antibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding that some well-established IBD therapeutics do not have any effect in the model highlights important differences between the experimental model and the human disease.

  3. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Min Jeoung Lee

    Full Text Available BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs. Although high concentrations of S100A9 protein and interleukin-6 (IL-6 are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. METHODS: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3 phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc and S100A9 small interfering (si RNA (si-S100A9 on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.

  4. Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

    Science.gov (United States)

    Lin, Yu Kuei; Faiman, Charles; Johnston, Philip C; Walsh, R Matthew; Stevens, Tyler; Bottino, Rita; Hatipoglu, Betul A

    2016-10-01

    Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. The study was conducted at a single institution (Cleveland Clinic). Patients included recipients of TP-IAT. The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

  5. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  6. Protective Effect of Laminaria japonica with Probiotics on Murine Colitis

    Directory of Open Access Journals (Sweden)

    Seok-Jae Ko

    2014-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN-γ, IL-1β, IL-6, IL-10, IL-12 (P40, IL-12 (P70, IL-17, and TNF-α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1β, IL-6, and IL-12 (P40 but not IFN-γ, IL-10, and IL-12 (P70. In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics.

  7. Periostal hypertrophic osteopathy of bones (long bones) in colitis ulcerosa in adolescents

    International Nuclear Information System (INIS)

    Bargon, G.; Arlart, I.

    1982-01-01

    The article reports on a 14-year old girl with periostal new formation of bones at the long bones of the lower arms, the femora and the lower legs the individual phalanges and metacarpalia after colitis ulcerosa which had lasted for several years and had progressed stagewise. After a clinically recorded new attack the periostal new formations of bone progressed. Some time after the last attack of colitis the periostal changes in the bones partially receded. The article discusses the hypothetic explanations aiming at interpreting the pathogenesis of hypertrophic osteoarthropathies and periostoses, as given in the literature. (orig.) [de

  8. Periostal hypertrophic osteopathy of bones (long bones) in colitis ulcerosa in adolescents

    Energy Technology Data Exchange (ETDEWEB)

    Bargon, G.; Arlart, I.

    1982-03-01

    The article reports on a 14-year old girl with periostal new formation of bones at the long bones of the lower arms, the femora and the lower legs the individual phalanges and metacarpalia after colitis ulcerosa which had lasted for several years and had progressed stagewise. After a clinically recorded new attack the periostal new formations of bone progressed. Some time after the last attack of colitis the periostal changes in the bones partially receded. The article discusses the hypothetic explanations aiming at interpreting the pathogenesis of hypertrophic osteoarthropathies and periostoses, as given in the literature.

  9. New Features of Molecular Diagnostics of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    A.S. Volkov

    2016-03-01

    Full Text Available The purpose of this study was to search for new molecular markers for the diagnosis of ulcerative colitis (UC. The study included 65 patients (range from 22 to 35 years, 24 men and 41 women with left-sided UC (Montréal classification, mild and moderate activity, infrequent (≤1/year relapses according to the inclusion/exclusion criteria in the research. Criteria of the diagnosis of UC corresponded to ECCO Consensus [11]. The duration of UC was 5.3 years. The control group included 30 healthy individuals. Molecular phenotyping of colon mucosa was processed with methods of proteomics. The data of the molecular interactions were received with STRING 10.0 database. Potentially new molecular markers of the development of UC were identified.

  10. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

    Science.gov (United States)

    Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

    2017-05-04

    Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (Ptofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (Ptofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. In patients with moderately to severely

  11. Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

    Science.gov (United States)

    Keulemans, Y C; Mok, K S; Slors, J F; Brink, M A; Gouma, D J; Tytgat, G N; Groen, A K

    1999-10-01

    Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

  12. Location and activity of ulcerative and Crohn's colitis by 111In leukocyte scan. A prospective comparison study

    International Nuclear Information System (INIS)

    Stein, D.T.; Gray, G.M.; Gregory, P.B.; Anderson, M.; Goodwin, D.A.; McDougall, I.R.

    1983-01-01

    A prospective blinded study comparing the 111 In leukocyte scan to barium enema, colonoscopy, or surgery or a combination of these, was carried out in 15 patients (10 with active ulcerative colitis and 5 with active Crohn's colitis). Correlation of disease location to colonic regions between indium scan and other diagnostic studies was excellent in 11 instances, good in 2, and poor in 3. In 2 of the 3 studies where major disagreement occurred, the comparative barium enema was performed greater than 2 mo after the indium scan. Disease activity, estimated by the intensity of radionuclide uptake, was compared to clinical disease activity assessed by the Crohn's Disease Activity Index for both forms of colitis. The relative degree of inflammation estimated by the indium scan correlated well with the independent clinical assessment (correlation coefficient . 0.81). The indium 111 leukocyte scan appears to be an accurate, noninvasive method for assessing the extent and the severity of the inflammation in patients with acute ulcerative or Crohn's colitis

  13. The Role of Syndrome Differentiation in the Clinical Efficacy of Punica Granatum on Patients with Ulcerative Colitis.

    Science.gov (United States)

    Kamali, Mohammadali; Khodadoost, Mahmoud; Tavakoli, Hamid; Kamalinejad, Mohammad; Gachkar, Latif; Adibi, Payman; Heydari, Mojtaba

    2016-05-01

    The present study investigated the difference between therapeutic responses of hot and cold temperament patients (based on traditional Persian medicine) with ulcerative colitis to pomegranate peel extract. Seventy-eight patients with moderate ulcerative colitis based on Lichtiger Colitis Activity Index (LCAI) criteria were randomized to receive an aqueous extract of the Punica granatum peel (6 gram per day) or placebo for four weeks. They were assessed before and after the intervention in terms of symptoms by LCAI scoring system. The results were compared in two therapeutic groups based on the patient s' temperament (cold and hot) which were diagnosed based on a previously validated questionnaire. Therapeutic response was significantly higher in patients with hot temperament compared to patients with cold temperament in the P. granatum group (1.91±0.492 vs. -0.500±0.500, P=0.029). This study showed the importance of considering syndrome differentiation and temperament in interpreting the effect of P. granatum peel extract on ulcerative colitis.

  14. Evaluation of spontaneous space closure and development of permanent dentition after extraction of hypomineralized permanent first molars.

    Science.gov (United States)

    Jälevik, Birgitta; Möller, Marie

    2007-09-01

    The aim of this study was to evaluate spontaneous space closure, development of the permanent dentition, and need for orthodontic treatment after extraction of permanent first molars due to severe molar-incisor hypomineralization (MIH). Twenty-seven children aged 5.6-12.7 (median 8.2) years had one to four permanent first molars extracted due to severe MIH. Each case was followed up on individual indications 3.8-8.3 (median 5.7) years after extractions. The eruption of the permanent dentition, and space closure were documented by orthopantomograms, casts, photographs, and/or bitewings. Fifteen children were judged to have a favourable spontaneous development of their permanent dentition without any orthodontic intervention. Seven children were or should be subjected to orthodontic treatment for other reasons registered prior to the extraction. Five children were judged to have a treatment at least caused by the extractions, but three of them abstained because of no subjective treatment need. Extraction of permanent first molars severely affected by MIH is a good treatment alternative. Favourable spontaneous space reduction and development of the permanent dentition positioning can be expected without any intervention in the majority of cases extracted prior to the eruption of the second molar.

  15. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

    NARCIS (Netherlands)

    Sandborn, William J.; Su, Chinyu; Sands, Bruce E.; D'Haens, Geert R.; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G.; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

    2017-01-01

    Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized,

  16. The wiring of developing sensory circuits - from patterned spontaneous activity to mechanisms of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Alexandra Helen Leighton

    2016-09-01

    Full Text Available In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012. In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (optogenetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we

  17. Osteonecrosis or spontaneous fractures following renal transplantation

    International Nuclear Information System (INIS)

    Andresen, J.; Nielsen, H.E.; Aarhus Univ.

    1981-01-01

    31 renal transplant recipients with posttransplant development of osteonecrosis or spontaneous fractures were evaluated with regard to age, duration of dialysis before transplantation. Determination of metacarpal bone mass at the time of transplantation and registration of bone resorption and soft tissue calcification at the time of transplantation and at the time of onset of osteonecrosis and spontaneous fractures were made. Apart from the increased mean age in patients with spontaneous fractures no difference was seen between the groups. Osteonecrosis and spontaneous fractures occurred in areas of trabecular bone. It seems most likely that after renal transplantation the patients show bone complications of different localization. (orig.) [de

  18. Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.

    Science.gov (United States)

    Petronilho, Fabricia; Michels, Monique; Danielski, Lucinéia G; Goldim, Mariana Pereira; Florentino, Drielly; Vieira, Andriele; Mendonça, Mariana G; Tournier, Moema; Piacentini, Bárbara; Giustina, Amanda Della; Leffa, Daniela D; Pereira, Gregório W; Pereira, Volnei D; Rocha, João Batista Teixeira Da

    2016-09-01

    The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis.

    Science.gov (United States)

    Rahimian, Reza; Zirak, Mohammad Reza; Keshavarz, Mojtaba; Fakhraei, Nahid; Mohammadi-Farani, Ahmad; Hamdi, Hanan; Mousavizadeh, Kazem

    2016-09-20

    Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT 3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1β diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ and decreased the MPO activity (p < .05). Tropisetron exerts notable anti-inflammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPARγ receptors.

  20. Dietary α-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice.

    Science.gov (United States)

    Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M; Berman-Booty, Lisa D; Galley, Jeffrey D; Chitchumroonchokchai, Chureeporn; Mace, Thomas; Suksamrarn, Sunit; Bailey, Michael T; Clinton, Steven K; Lesinski, Gregory B; Failla, Mark L

    2014-06-01

    Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Influence of dietary isoflavone intake on gastrointestinal symptoms in ulcerative colitis individuals in remission.

    Science.gov (United States)

    Głąbska, Dominika; Guzek, Dominika; Grudzińska, Dominika; Lech, Gustaw

    2017-08-07

    To analyse the association between isoflavone intake and ulcerative colitis motility symptoms in individuals in remission. Cross-sectional study was conducted in a group of ulcerative colitis remission individuals, in sub-groups characterised by various intestinal motility and functioning characteristics (abdominal pain, flatulence, constipations, tenesmus). Total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. Assessment of diet was based on self-reported data from each patient's dietary records taken over a period of three typical, random days (2 weekdays and 1 d of the weekend). The daily isoflavone intake (daidzein, genistein, glycitein and total isoflavones) and daily isoflavone intake per 1000 kcal of diet were assessed. No correlations between isoflavone intake levels and number of bowel movements per day were observed both in the case of intake and intake per 1000 kcal of diet. In the group of individuals declaring lack of abdominal pain, the higher intakes of daidzein ( P = 0.0075), daidzein per 1000 kcal of diet ( P = 0.0358) and total isoflavone ( P = 0.0358) were stated, than in the group of individuals declaring abdominal pain. In the group of individuals declaring lack of constipations, the lower intakes of glycitein ( P = 0.0213) and glycitein per 1000 kcal of diet ( P = 0.0213) were stated, than in the group of individuals declaring presence of constipations. No differences were observed in isoflavone intake between groups of ulcerative colitis individuals declaring lack of flatulence and declaring presence of flatulence, as well as between groups declaring lack of tenesmus and declaring presence of tenesmus. The moderate dietary isoflavone intake may be beneficial for individuals with ulcerative colitis in remission, however, before including it into recommendations, further prospective studies are needed.

  2. Fæcestransplantation som behandling af Clostridium difficile-infektion, colitis ulcerosa og metabolisk syndrom

    DEFF Research Database (Denmark)

    Carstensen, Jeppe West; Hansen, Axel Kornerup

    2014-01-01

    Faecal transplantation as a treatment for Clostridium difficile infection, ulcerative colitis and the metabolic syndrome Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial......, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal...... transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection....

  3. The early manifestation of Yersinia colitis demonstrated by the double-contrast barium enema

    International Nuclear Information System (INIS)

    Aspestrand, F.

    1986-01-01

    A 19-year old female with a bloody, diarrheal illness of acute onset where Crohn's disease primarly was suspected is presented. The double-contrast barium enema revealed multiple, diffusely scattered aphthous erosions of the colonic mucosa: the rectum was scarcely affected. Biopsies taken by endoscopy demonstrated nonspecific inflammatory changes of the mucous membrane. However, routinely taken stool cultures revealed an infectious colitis due to Yersinia enterocolitica. Our case demonstrates the necessity to consider Yersinia enterocolitis in the radiographic differential diagnosis when the diagnosis of Crohn's disease or ulcerative colitis seems obvious. (orig.) [de

  4. Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, J G; Kjeldsen, J; Schmidt, P T

    2002-01-01

    BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous...... B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after......: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics....

  5. An update on anti-TNF agents in ulcerative colitis

    NARCIS (Netherlands)

    Samaan, Mark A.; Bagi, Preet; Vande Casteele, Niels; D'Haens, Geert R.; Levesque, Barrett G.

    2014-01-01

    Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their

  6. Demography and clinical course of ulcerative colitis in a multiracial Asian population: a nationwide study from Malaysia.

    Science.gov (United States)

    Hilmi, I; Singh, R; Ganesananthan, S; Yatim, I; Radzi, M; Chua, A B S; Tan, H J; Huang, S; Chin, K S; Menon, J; Goh, K L

    2009-02-01

    To establish the clinical course of ulcerative colitis (UC) in the Malaysian population, comparing the three major ethnic groups: Malay, Chinese and Indian. Patients who were diagnosed with UC from seven major medical referral centers in Malaysia were recruited. Their baseline characteristics, and the extent of the disease, its clinical course and complications were recorded. A total of 118 patients was included. The extent of disease was as follows: proctitis alone in 22 (18.6%), sigmoid colon in 23 (19.5%), descending colon in 16 (13.6%), transverse colon in 11 (9.3%), ascending colon and pancolitis 46 (39%). Most patients had chronic intermittent disease. Extra-intestinal complications were seen in 27 (22.9%) patients and fulminant colitis was seen in four (3.4%). None developed colorectal cancer. The overall cumulative colectomy rates at 1, 5 and 10 years were 3.4% (CI: 0.9-8.5), 5.9% (CI: 1.9-13.2) and 15.6% (CI: 6.5-29.4), respectively. There was a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease among Indian patients. However, no significant differences were seen in the age of onset, the severity of disease (fulminant colitis, refractory disease) and the colectomy rate. As in developed countries, most of our patients have a remitting and relapsing pattern of disease but the clinical course appears to be milder, with lower rates of colectomies. There are differences in clinical presentation among the three major ethnic groups, with Indians having a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease.

  7. Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Rohta Noaki

    2009-11-01

    Full Text Available A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications.

  8. Granulomatous colitis: findings on double contrast barium enema and follow-up studies

    International Nuclear Information System (INIS)

    Song, Jong Gi; Han, Joon Koo; Kim, Seung Hoon; Choo, Sung Wook; Kim, Seung Cheol; Choi, Byung Ihn

    1995-01-01

    To evaluate the radiologic findings of granulomatous colitis on double contrast barium enema and changes on follow-up studies. Serial double contrast barium enema of six patients with granulomatous colitis confirmed by endoscopic biopsy were reviewed. We analyzed the radiologic findings and their follow-up changes, including aphthous ulcers, lymphoid hyperplasia, deep ulcers, cobble stone appearance, geographic ulcers, asymmetric involvement of ulcers, skip lesions, sinus tract, fistula formation, pseudosacculation, focal stricture, and small bowel involvement. Pretreatment double contrast barium enema findings were aphthous ulcers in five patients, deep ulcer in six, cobble stone appearance in five, longitudinal geographic ulcers in two, fistulas in one, pseudosacculations in two, focal stricture in one, and pseudopolyps in six. Also, anal ulcers were observed in two patients, asymmetric involvement of ulcers in three, skip lesions in four, and small bowel involvement in five in five patients proved to have inactive disease after treatment, aphthous ulcers and deep ulcers disappeared. Geographic ulcers of two patients and anal ulcer of one patients decreased in size or depth. Pseudosacculation in one patient disappeared. Pseudopolyps decreased in two patients, increased in one, and decreased after increase in two. One patient whose disease remained active after treatment showed maintenance or increase of ulcers or fistula. And their pseudosacculation or focal stricture unchanged and pseudopolyps decreased. The major radiologic findings of chronic granulomatous colitis on double contrast barium enema are aphthous ulcer, deep ulcer, cobble stone appearance, discontinuity of the lesion and coexistence of ulcers and pseudopolyps. And, double contrast barium enema is good follow-up modality because its findings correlate with clinical course of the granulomatous colitis after treatment

  9. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  10. No Protection against DSS-induced Colitis by Short-term Pretreatment with Seal or Fish Oils in Rats

    Directory of Open Access Journals (Sweden)

    Gülen Arslan

    2007-01-01

    Full Text Available Background: Omega-3 (n-3 polyunsaturated fatty acids (PUFAs have modulating effects in several chronic inflammatory conditions. The aim of the present study was to test whether prior short-term dietary supplementation with n-3 (fish or seal oil or n-6 (soy oil PUFA rich oils would protect the development of dextran sulfate sodium (DSS-induced colitis in rats.Methods: Forty-eight male Wistar rats were divided into 6 groups: no intervention, sham, DSS, seal oil + DSS, fi sh oil +DSS and soy oil + DSS. Following 7 days of acclimatisation, 1 mL oil (seal, fish or soy or distilled water (sham was administered by gavage day 8 to 14. Colitis was induced by 5% DSS in drinking water from day 15 to 21. Rats were sacrificed on day 23. Histological colitis (crypt and inflammation scores, faecal granulocyte marker protein (GMP and quantitative fatty acid composition in red blood cells were measured.Results: Pretreatment with fish or seal oils did not significantly influence DSS induced inflammation. In fact, all the oils tended to exacerbate the inflammation. Soy oil increased the mean crypt score (P < 0.04, but not the inflammation score or GMP. The ratio of n-6 to n-3 fatty acids (FAs was 11 to 1 and 10 to 1 in standard diet and in red blood cells of control rats, respectively. Following administration of DSS, the ratio fell in all treatment groups (P < 0.001. The lowest ratios were seen in the groups receiving DSS + fi sh or seal oils (around 6 to 1.Conclusion: Short-term pretreatment with fish or seal oils did not protect against subsequent induction of colitis by DSS in this rat model. Whether the high ratio of n-6 to n-3 FAs in the standard diet concealed effects of n-3 FA supplementation should be further investigated.

  11. Lethal Clostridium difficile Colitis Associated with Paclitaxel and Carboplatin Chemotherapy in Ovarian Carcinoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    V. Masciullo

    2010-01-01

    Full Text Available Clostridium difficile colitis, although rare, could represent a serious complication following chemotherapy. Prior antibiotic use has been considered the single most important risk factor in the development of C. difficile infection. Recently, the association between antineoplastic therapy and C. difficile-associated diarrhea in the absence of a prior antibiotic therapy has become more apparent. A 75-year-old woman with serous adenocarcinoma of the ovary developed lethal pancolitis caused by C. difficile after five cycles of paclitaxel- and carboplatin-based chemotherapy. She presented with diarrhea, coffee-ground emesis, and oliguria and was hospitalized immediately for aggressive treatment. Despite all the medical efforts, her condition worsened and she died after twenty days. We describe the second case reported of a patient developing a severe C. difficile colitis following chemotherapy without any recent antibiotic use and review the data of the literature, emphasizing the need to a prompt diagnosis and management that can significantly decrease the morbidity and life-threatening complications associated with this infection.

  12. Fidaxomicin in the treatment of colitis due to Clostridium difficile: preliminary results

    Directory of Open Access Journals (Sweden)

    Francesco Cortese

    2014-12-01

    Full Text Available The incidence of Clostridium difficile infections (CDI and Clostridium difficile-Associated Diarrhea (CDAD is increasing in Canada, USA, and Europe and represents a considerable clinical problem. Both naïve and hypervirulent strains can be considered as opportunistic bacteria affecting immunocompromised, antibiotic-treated, critical, or subcritical patients with a microbiota disruption. CDI arising is strictly related to antibiotic, single or combined, and/or proton pump inhibitor treatment. CDI can cause a syndrome with systemic involvement and complex treatment, sometimes requiring surgical interventions (e.g. colectomy in fulminant colitis. Antibiotic treatment with metronidazole by mouth is the first choice and generally vancomycin is administered in case of lack of effectiveness. Fidaxomicin is a new macrocyclic antibiotic for C. difficile with microflora-sparing properties. This paper reports our initial experience in 11 patients with non-responder or relapsing CDIs. Fidaxomicin was effective in 10 cases (91%. Only one patient with an active ulcerative colitis did not respond and was treated with fecal-microbiota transplantation. In two patients diarrhea persisted, but just the ulcerative colitis one was C. difficile-related. No adverse events were experienced.http://dx.doi.org/10.7175/cmi.v8i1s.956

  13. Lower first permanent molars: developing better predictors of spontaneous space closure.

    Science.gov (United States)

    Teo, Terry Kuo-Yih; Ashley, Paul Francis; Derrick, Donald

    2016-02-01

    First, first permanent molars (FPMs) of poor prognosis are often planned for extraction at an 'ideal time' so that second permanent molars (SPMs) erupt favourably to replace them. However for lower FPM extractions, timing is not an accurate predictor of success. The aim of this study was to identify additional radiographic factors that could better predict the degree of spontaneous space closure of the lower SPM following FPM extraction. Data from a previous study of 127 lower SPMs from 66 patients was re-analysed by incorporating additional radiographic factors. These included calcification stage of the bifurcation of the SPM, position of the second premolar, mesial angulation of SPM in relation to the FPM, and presence of the third permanent molar. Results were analysed using ordered logistic regression. Only 58 per cent of FPMs extracted at the 'ideal time' (SPM development at Demirjian stage E) had complete space closure. The best outcomes resulted from a combination of SPMs not at Demirjian development stage G, together with the presence of mesial angulation of the SPM and presence of the third permanent molar, where 85 per cent of those cases had complete space closure. Apart from extraction timing of the FPM, consideration must also be given to the presence of the third permanent molar and angulation of the SPM in order to ensure a reliable degree of spontaneous space closure of the lower SPM. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Spontaneous onset of Complex Regional Pain Syndrome

    NARCIS (Netherlands)

    de Rooij, A.M.; Perez, R.S.G.M.; Huygen, F.J.; van Eijs, F.; van Kleef, M.; Bauer, M.C.R.; van Hilten, J.J.; Marinus, J.

    2010-01-01

    Complex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly debated and the aim of the present study was therefore to compare the phenotypic characteristics of CRPS

  15. The Proteome of Ulcerative Colitis in Colon Biopsies from Adults - Optimized Sample Preparation and Comparison with Healthy Controls.

    Science.gov (United States)

    Schniers, Armin; Anderssen, Endre; Fenton, Christopher Graham; Goll, Rasmus; Pasing, Yvonne; Paulssen, Ruth Hracky; Florholmen, Jon; Hansen, Terkel

    2017-12-01

    The purpose of the study was to optimize the sample preparation and to further use an improved sample preparation to identify proteome differences between inflamed ulcerative colitis tissue from untreated adults and healthy controls. To optimize the sample preparation, we studied the effect of adding different detergents to a urea containing lysis buffer for a Lys-C/trypsin tandem digestion. With the optimized method, we prepared clinical samples from six ulcerative colitis patients and six healthy controls and analysed them by LC-MS/MS. We examined the acquired data to identify differences between the states. We improved the protein extraction and protein identification number by utilizing a urea and sodium deoxycholate containing buffer. Comparing ulcerative colitis and healthy tissue, we found 168 of 2366 identified proteins differently abundant. Inflammatory proteins are higher abundant in ulcerative colitis, proteins related to anion-transport and mucus production are lower abundant. A high proportion of S100 proteins is differently abundant, notably with both up-regulated and down-regulated proteins. The optimized sample preparation method will improve future proteomic studies on colon mucosa. The observed protein abundance changes and their enrichment in various groups improve our understanding of ulcerative colitis on protein level. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Butyrate absorption and lactate secretion in ulcerative colitis

    DEFF Research Database (Denmark)

    Hove, H; Holtug, K; Jeppesen, P B

    1995-01-01

    .12. Despite normal butyrate absorption, sodium absorption was compromised in active ulcerative colitis (11.5 +/- 1.4 mumol/cm2/h) compared with quiescent (15.4 +/- 1.0 mumol/cm2/h) and controls (18.7 +/- 0.8 mumol/cm2/h) (P = 0.0006). Mucosal secretion of L-lactate was minimal in both healthy controls...

  17. Mindfulness May Be Helpful for People with Ulcerative Colitis

    Science.gov (United States)

    ... homework. This was compared to a “time/attention” control—a course on mind and body medicine that was similar in format but did not include coping skills, practice, or any information on ulcerative ... the MBSR and control groups in the course of ulcerative colitis disease, ...

  18. Sclerosing cholangitis with ulcerative colitis in a Nigerian woman ...

    African Journals Online (AJOL)

    Primary Sclerosing Cholangitis (PSC) is a relatively rare cause of chronic liver disease worldwide. It presents as chronic cholestasis associated with jaundice and pruritus. We report a middle aged Nigerian woman who presented with cholestatic jaundice and diagnosed with PSC with concurrent ulcerative colitis based on ...

  19. The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility.

    Science.gov (United States)

    Escalante, Nichole K; Lemire, Paul; Cruz Tleugabulova, Mayra; Prescott, David; Mortha, Arthur; Streutker, Catherine J; Girardin, Stephen E; Philpott, Dana J; Mallevaey, Thierry

    2016-12-12

    The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1 -/- mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research. © 2016 Escalante et al.

  20. L’habitat spontané comme un outil de développement urbain. Le cas de Bangkok Spontaneous Housing as a Tool for Urban Development, the Case of Bangkok

    Directory of Open Access Journals (Sweden)

    Fanny Gerbeaud

    2011-10-01

    approached the spontaneous settlements as a construction process based on appropriation : at least three forms of spontaneous housing (pure, ancient and “grafted” integrate progressively the urban fabric and ensure by its flexibility its continuity. If, for local authorities, slum communities remain a sign of underdevelopment, some architects and actors see it as a source of inspiration and a popular heritage to preserve. In this context, the growing metropolization and the globalization of economical, cultural and political exchanges bring new ways of negotiating urban space, redefining the status of the settlements. With the emergence of new professions (community architect and directions in urban planning projects (in particular the participatory process informal settlements gradually become a tool for the development of the capital.

  1. Association between gastrointestinal motility and macrophage/mast cell distribution in mice during the healing stage after DSS‑induced colitis.

    Science.gov (United States)

    Kodani, Mio; Fukui, Hirokazu; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

    2018-06-01

    Irritable bowel syndrome (IBS) frequently occurs after infectious colitis or inflammatory bowel disease in patients with complete remission. This suggests that post‑inflammation‑associated factors may serve a role in the pathophysiology of IBS; however, the mechanism responsible remains unclear. In the present study, the involvement of macrophages and mast cells in alteration of gastrointestinal (GI) motility was investigated in mice in the remission stage after acute colitis. C57BL/6 mice were administered 2% dextran sulfate sodium in drinking water for 5 days and their intestinal tissues were investigated at intervals for up to 24 weeks. Expression of the mannose receptor (MR) and tryptase was examined by immunohistochemistry, and the GI transit time (GITT) was measured by administration of carmine red solution. A minimal degree of inflammatory cell infiltration persisted in the colon and also the small intestine of mice in remission after colitis and the GITT was significantly shorter. The number of muscularis MR‑positive macrophages was significantly increased in the small intestine of mice in remission after colitis and negatively correlated with GITT. Furthermore, results indicated that the number of muscularis tryptase‑positive mast cells was significantly increased throughout the intestine of mice during the healing process after colitis and was positively correlated with GITT. The present findings suggested an increased number of macrophages and/or mast cells in the intestinal muscular layer may be associated with the pathophysiology of GI dysmotility after colitis.

  2. Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

    Science.gov (United States)

    Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

    2010-09-07

    To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

  3. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.

    Science.gov (United States)

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-09

    Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with

  4. Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.

    Science.gov (United States)

    Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Kuśnierz-Cabala, Beata; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Gil, Krzysztof; Olszanecki, Rafał; Pihut, Małgorzata; Dembiński, Artur

    2017-05-24

    Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

  5. G protein-coupled receptor kinase-2-deficient mice are protected from dextran sodium sulfate-induced acute colitis.

    Science.gov (United States)

    Steury, Michael D; Kang, Ho Jun; Lee, Taehyung; Lucas, Peter C; McCabe, Laura R; Parameswaran, Narayanan

    2018-06-01

    G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays a key role in different disease processes. Previously, we showed that GRK2 knockdown enhances wound healing in colonic epithelial cells. Therefore, we hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate (DSS)-induced acute colitis. To test this, we administered DSS to wild-type (GRK2 +/+ ) and GRK2 heterozygous (GRK +/- ) mice in their drinking water for 7 days. As predicted, GRK2 +/- mice were protected from colitis as demonstrated by decreased weight loss (20% loss in GRK2 +/+ vs. 11% loss in GRK2 +/- ). lower disease activity index (GRK2 +/+ 9.1 vs GRK2 +/- 4.1), and increased colon lengths (GRK2 +/+ 4.7 cm vs GRK2 +/- 5.3 cm). To examine the mechanisms by which GRK2 +/- mice are protected from colitis, we investigated expression of inflammatory genes in the colon as well as immune cell profiles in colonic lamina propria, mesenteric lymph node, and in bone marrow. Our results did not reveal differences in immune cell profiles between the two genotypes. However, expression of inflammatory genes was significantly decreased in DSS-treated GRK2 +/- mice compared with GRK2 +/+ . To understand the mechanisms, we generated myeloid-specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was sufficient for the protection from DSS-induced colitis. Together our results indicate that deficiency of GRK2 protects mice from DSS-induced colitis and further suggests that the mechanism of this effect is likely via GRK2 regulation of inflammatory genes in the myeloid cells.

  6. Treatment tactics in patient with rectal cancer complicating ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Yu. A. Barsukov

    2012-01-01

    Full Text Available A successful treatment of a young patient with a 15-year anamnesis of ulcerative colitis, who has been diagnosed with rectal cancer, is presented in this case report. A non-standard surgical intervention has been performed following all principles of oncologic surgery. A subtotal colectomy has been performed with ultra-low anterior resection of rectum. Ascendoanal anastomosis has been performed forming the neo-rectum. There were no complications in postoperative period. Considering disease stage (T3N1M0 adjuvant XELOX was administered for 6 months along with 2 cycles of prophylactic treatment with 5-aminosalycilic acid. During 2-years follow-up there are no signs of rectal cancer and ulcerative colitis progression. After pelvic electrostimulation defecation frequency decreased to 3–4 times per day, a patient has complete social rehabilitation.

  7. Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis

    DEFF Research Database (Denmark)

    Mark-Christensen, A; Erichsen, R; Brandsborg, S

    2018-01-01

    BACKGROUND: The ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain risk factors associated with failure. METHOD: 1,991 patients with ulc......BACKGROUND: The ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain risk factors associated with failure. METHOD: 1,991 patients......-anal anastomosis from Denmark, where pouch surgery is centralized, females had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure. This article is protected by copyright. All rights reserved....

  8. Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

    Science.gov (United States)

    Mizukami, Tomoyuki; Obara, Megumi; Nishikomori, Ryuta; Kawai, Tomoki; Tahara, Yoshihiro; Sameshima, Naoki; Marutsuka, Kousuke; Nakase, Hiroshi; Kimura, Nobuhiro; Heike, Toshio; Nunoi, Hiroyuki

    2012-02-01

    X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

  9. In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

    International Nuclear Information System (INIS)

    Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A.; Porzner, M.; Seufferlein, T.; Metz, H.; Maeder, K.; Christ, B.

    2015-01-01

    The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

  10. In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A. [Martin Luther University Halle-Wittenberg, Department of Internal Medicine I, Halle (Germany); Porzner, M.; Seufferlein, T. [University of Ulm, Department of Internal Medicine I, Ulm (Germany); Metz, H.; Maeder, K. [Martin Luther University, Institut of Pharmacy, Halle-Wittenberg (Germany); Christ, B. [University of Leipzig, Department of Surgery II, Leipzig (Germany)

    2015-10-15

    The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

  11. An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation.

    Science.gov (United States)

    Çatlı, Gönül; Alparslan, Caner; Can, P Şule; Akbay, Sinem; Kelekçi, Sefa; Atik, Tahir; Özyılmaz, Berk; Dündar, Bumin N

    2015-06-01

    46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.

  12. Environmental factors in infancy and ulcerative colitis in the Central South of Chile: a case-control study.

    Science.gov (United States)

    Boneberger, Anja; Weiss, Eduardo Hebel; Calvo, Mario; Torres, Lilibeth; Wagner, Johanna; Kabesch, Michael; Radon, Katja

    2011-10-01

    Evidence for the role of the hygiene hypothesis and the development of Ulcerative Colitis (UC) is unclear. We aimed to explore the association between environmental factors in infancy and UC. A hospital-based case-control study (52 UC cases, response: 77%, 174 age- , sex and place of living matched controls, response: 62%) was carried out in the Central South of Chile in 2009/2010. Patients or parents underwent a personal interview about early life experiences. High paternal education (adjusted Odds Ratio (aOR): 2.1; 95% CI: 1.0-4.5) as proxy for socioeconomic status was positively associated with case status in the final multivariate logistic regression model. Likewise, having older siblings was a risk factor for UC (aOR: 2.2; 95%CI: 1.1.-4.4). The importance for some early life environmental factors in the development of UC was established. However, the role of the hygiene hypothesis could not be confirmed for all environmental factors. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  13. Optimal management of steroid-dependent ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Khan HMW

    2015-11-01

    Full Text Available Hafiz M Waqas Khan,1 Faisal Mehmood,1 Nabeel Khan2 1Department of Medicine, King Edward Medical University, Lahore, Pakistan; 2Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA Abstract: Ulcerative colitis (UC is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date. Keywords: ulcerative colitis, steroid dependent, thiopurines, MTX, adalimumab, infliximab

  14. Golimumab for the treatment of ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Löwenberg M

    2014-03-01

    Full Text Available Mark Löwenberg,1 Nanne KH de Boer,2 Frank Hoentjen3 1Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands; 2Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, the Netherlands; 3Inflammatory Bowel Disease Center, Radboud University Medical Center, Nijmegen, the Netherlands Abstract: The introduction of therapeutic antibodies against tumor necrosis factor (TNF had a major impact on the treatment of ulcerative colitis (UC. Infliximab and adalimumab are powerful agents that are used for remission induction and maintenance therapy in UC and have an acceptable safety profile. However, a proportion of UC patients for whom therapy with anti-TNF agents is indicated fail or become intolerant to treatment with infliximab or adalimumab. Hence, there remains an unmet need for novel anti-TNF agents. Golimumab (Simponi®, a human anti-TNF antibody that is administered by monthly subcutaneous injections, is the most recently introduced TNF blocker for the treatment of UC. Here, we will discuss recent literature on clinical efficacy and safety of golimumab induction and maintenance treatment in patients with UC. Furthermore, we will discuss the positioning of golimumab for UC in current treatment algorithms. Keywords: ulcerative colitis, UC, antitumor necrosis factor, TNF, antibodies, golimumab

  15. An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

    Science.gov (United States)

    Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

    2018-04-19

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

  16. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    Science.gov (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  17. Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.

    Science.gov (United States)

    Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine; Laukens, Debby

    2017-04-01

    The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila , bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD. IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we

  18. Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS in Mice Treated with FR91

    Directory of Open Access Journals (Sweden)

    Valter R. M. Lombardi

    2012-01-01

    Full Text Available One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC. However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS. Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

  19. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  20. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    International Nuclear Information System (INIS)

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong; Gu, Yan-Hong; Shen, Yan; Tan, Ren-Xiang; Sun, Yang; Xu, Qiang

    2012-01-01

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  1. Spontaneous pneumothorax in diffuse cystic lung diseases.

    Science.gov (United States)

    Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant

    2017-07-01

    Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

  2. Development of fermented milk “Leben” made from spontaneous ...

    African Journals Online (AJOL)

    Yomi

    2012-01-24

    Jan 24, 2012 ... shaking it back and forth till the coalescence of the fat globules. ... proteins, mesophilic lactis acid bacteria (LAB) were the predominant ... the following steps: five liters of raw milk was left spontaneously at. 25 ± 2°C in a jar ...

  3. Effects of a novel encapsulating technique on the temperature tolerance and anti-colitis activity of the probiotic bacterium Lactobacillus kefiranofaciens M1.

    Science.gov (United States)

    Wang, Sheng-Yao; Ho, Yi-Fang; Chen, Yen-Po; Chen, Ming-Ju

    2015-04-01

    Lactobacillus kefiranofaciens M1 (M1) has been shown to possess many different beneficial health effects including anti-colitis activity. The purpose of this study was to develop a novel and easily scaled-up encapsulating technique that would improve the temperature tolerance of the bacterium and reduce the sensitivity of the organism to gastrointestinal fluid. A mixture of sodium alginate, gellan gum and skim milk powder was used as a coating material to entrap M1. The M1 gel was then directly freeze dried in order to dehydrate the covering and form microcapsules. The viable cell numbers of M1 present only dropped ten folds after the freeze-drying encapsulation process. The viable cell counts remained constant at 5 × 10(7) CFU/g after heating from 25 °C to 75 °C and holding at 75 °C for 1 min. The viable cell counts were reduced to 10(6) CFU/g and 10(5) CFU/g after 8-week storage at 4 °C and subsequent heat treatment with simulated gastrointestinal fluid test (SGFT) and bile salts, respectively. The effect of encapsulated M1 on the organism's anti-colitis activity was evaluated using the dextran sodium sulfate (DSS) induced colitis mouse model. An in vivo study indicated that administration of heat treated encapsulated M1 was able to ameliorate DSS-induced colitis producing a significant reduction in the bleeding score and an attenuation of inflammatory score. These findings clearly demonstrate that encapsulation of M1 using this novel technique is able to provide good protection from temperature changes and SGFT treatment and also does not affect the organism's anti-colitis activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

    Science.gov (United States)

    Islam, M S; Murata, T; Fujisawa, M; Nagasaka, R; Ushio, H; Bari, A M; Hori, M; Ozaki, H

    2008-01-01

    Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-κB (NF-κB) activity in macrophages. In the present study, we investigated the effect of γ-oryzanol (γ-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of γ-ORZ, and ferulic acid (FA), a possible metabolite of γ-ORZ in vivo, on a model of colitis in mice. Experimental approach: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-κB activity in colitis tissue. Key results: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-κB p65 nuclear translocation and inhibitory protein of nuclear factor-κB-α degradation levels were significantly increased in DSS-induced colitis tissues. γ-ORZ (50 mg kg−1 day−1 p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that γ-ORZ and CAF had strong antioxidant effects comparable to those of α-tocopherol. Conclusions and implications: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-κB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates. PMID:18536734

  5. Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

    Science.gov (United States)

    Montoro, Miguel A; Brandt, Lawrence J; Santolaria, Santos; Gomollon, Fernando; Sánchez Puértolas, Belén; Vera, Jesús; Bujanda, Luis; Cosme, Angel; Cabriada, José Luis; Durán, Margarita; Mata, Laura; Santamaría, Ana; Ceña, Gloria; Blas, Jose Manuel; Ponce, Julio; Ponce, Marta; Rodrigo, Luis; Ortiz, Jacobo; Muñoz, Carmen; Arozena, Gloria; Ginard, Daniel; López-Serrano, Antonio; Castro, Manuel; Sans, Miquel; Campo, Rafael; Casalots, Alex; Orive, Víctor; Loizate, Alberto; Titó, Lluçia; Portabella, Eva; Otazua, Pedro; Calvo, M; Botella, Maria Teresa; Thomson, Concepción; Mundi, Jose Luis; Quintero, Enrique; Nicolás, David; Borda, Fernando; Martinez, Benito; Gisbert, Javier P; Chaparro, María; Jimenez Bernadó, Alfredo; Gómez-Camacho, Federico; Cerezo, Antonio; Casal Nuñez, Enrique

    2011-02-01

    There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

  6. Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner.

    Directory of Open Access Journals (Sweden)

    Dagmar Srutkova

    Full Text Available Reduced microbial diversity has been associated with inflammatory bowel disease (IBD and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis.Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952 and CCDM 372 (Bl 372 were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS-induced colitis was used to compare their beneficial effects in vivo.The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum.We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

  7. Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

    Science.gov (United States)

    Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

    2015-02-01

    Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

  8. Retrotransposition of long interspersed nucleotide element-1 is associated with colitis but not tumors in a murine colitic cancer model.

    Directory of Open Access Journals (Sweden)

    Takeshi Otsubo

    Full Text Available Long interspersed element-1 (L1 is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal carcinoma. However, how L1-retrotransposition (L1-RTP is involved in gastrointestinal disorders remains to be elucidated. We hypothesized that L1-RTP in somatic cells might contribute to colitis-associated cancer (CAC. To address this, we employed an experimental model of CAC using transgenic L1-reporter mice carrying a human L1-EGFP reporter gene. Mice were subjected to repeated cycles of colitis induced by administration of dextran sodium sulfate (DSS in drinking water with injection of carcinogen azoxymethane (AOM. L1-RTP levels were measured by a quantitative polymerase chain reaction targeting the newly inserted reporter EGFP in various tissues and cell types, including samples obtained by laser microdissection and cell sorting with flow cytometry. DNA methylation levels of the human L1 promoter were analyzed by bisulfite pyrosequencing. AOM+DSS-treated mice exhibited significantly higher levels of L1-RTP in whole colon tissue during the acute phase of colitis when compared with control naïve mice. L1-RTP levels in whole colon tissue were positively correlated with the histological severity of colitis and degree of neutrophil infiltration into the lamina propria (LP, but not with tumor development in the colon. L1-RTP was enriched in LP mesenchymal cells rather than epithelial cells (ECs, myeloid, or lymphoid cells. DNA methylation levels of the human L1 promoter region showed a negative correlation with L1-RTP levels. L1-RTP was absent from most tumors found in 22-week-old mice. In conclusion, we demonstrated that L1-RTP was induced in the mouse CAC mucosa in accordance with the acute inflammatory response; however, retrotransposition appears

  9. Faecal Bacterial Communities in Healthy Controls and Ulcerative Colitis Patients

    DEFF Research Database (Denmark)

    Vigsnæs, Louise Kristine; Wilcks, Andrea; Brynskov, Jørn

    Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) that is characterized by chronic inflammation of the colonic mucosa. The aetiology of IBD is not well understood, however the commensal intestinal microbiota is thought to play an important pathogenetic role. Hence...

  10. Protective effects of two Astragalus species on ulcerative colitis in rats

    African Journals Online (AJOL)

    management of UC are corticosteroids, 5- ... toothache, and neck pain, or orally for treating .... Macroscopic assessment of ulcerative colitis ... (version 8) software package (SPSS Inc, USA). ..... University Press, Edinburgh, 1970: 49–254. 6.

  11. Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Jahidul Islam

    2017-07-01

    Full Text Available Rice bran (RB is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group by dextran sodium sulfate (DSS. Body weight change, disease activity index (DAI, histopathology score, tissue myeloperoxidase (MPO activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript (Tnf-α, Il-1β, Il-6, and Il-17 levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis.

  12. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.

    Science.gov (United States)

    Hainzl, Eva; Stockinger, Silvia; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit; Müller, Mathias

    2015-11-15

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Okada, Toshihiko; Otsubo, Takeshi; Hagiwara, Teruki; Inazuka, Fumika; Kobayashi, Eiko; Fukuda, Shinji; Inoue, Takuya; Higuchi, Kazuhide; Kawamura, Yuki I; Dohi, Taeko

    2017-09-01

    Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro . Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum . Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro . In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

  14. Advanced colonic cancer associated with radiation colitis, report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Matsumoto, Takayuki [Kyushu Univ., Fukuoka (Japan). Hospital

    2002-07-01

    A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

  15. Advanced colonic cancer associated with radiation colitis, report of a case

    International Nuclear Information System (INIS)

    Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo; Matsumoto, Takayuki

    2002-01-01

    A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

  16. Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, J.G.; Kjeldsen, J.; Schmidt, P.T.

    2002-01-01

    reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis.Methods: In a randomized, double-blind, placebo-con trolled study, concentrations of leukotriene B-4...... rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon.Results: No significant...... changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon.Conclusions: These findings...

  17. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies......, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability....

  18. [Clinical extraintestinal manifestations in patients with ulcerative colitis].

    Science.gov (United States)

    Toader, Elena

    2007-01-01

    Ulcerative colitis (UC) is a chronic disease clinically manifest either by bowel symptoms alone or extraintestinal symptoms. Our prospective study included 635 patients with ulcerative colitis (334 males and 301 females, mean age 37.54 +/- 13.84, range 20-70 years). The presence of the common extraintestinal symptoms (ES) was analyzed. Of the 635 investigated patients, these symptoms were found in 83 (13%, 49 males and 34 females, mean age 41.6 +/- 13.95 range 21-70). Patients with ES suffered longer from UC on the average, that is 60.6 years. Most commonly ES involved the joints, 38 (45.8%) patients, hepatobiliary, 28 patients (33.7%), skin, 10 patients (12%) and eyes, 7 patients (8.4%). In 18% of the patients two or more ES were present. ES were clinically detectable after the intestinal symptoms in 81% patients. An increased tendency of ES to occur in patients with a more extensive disease was noticed. The prevalence of ES in the UC patients from NE Romania is in agreement with data from other countries. The number of ES supports the need for complex follow-up in these patients.

  19. Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

    DEFF Research Database (Denmark)

    Perner, Anders; Lassen, Inge Nordgaard; Matzen, Peter

    2002-01-01

    BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients...... by neutron activation analysis and the chemiluminescence technique, respectively. RESULTS: The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25...... higher (P gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method...

  20. Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-α antagonists

    Directory of Open Access Journals (Sweden)

    Fausel R

    2015-01-01

    Full Text Available Rebecca Fausel,1 Anita Afzali1,2 1Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA; 2Inflammatory Bowel Disease Program, UW Medicine – Harborview Medical Center, Seattle, WA, USA Abstract: Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. Keywords: ulcerative colitis, inflammatory bowel disease, infliximab, adalimumab, golimumab

  1. Immunohistochemical study of p53 overexpression in radiation-induced colon cancers

    International Nuclear Information System (INIS)

    Minami, Kazunori; Hayashi, Nobuyuki; Mokarim, A.; Matsuzaki, Sumihiro; Ito, Masahiro; Sekine, Ichiro.

    1998-01-01

    The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation-induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to 77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma (33%), a much higher than found for spontaneous mucinous cancer. Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. χ 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes'' classification. In radiation colitis around the cancers including aberrant crypts, spotted p53 staining and abnormal and scattered PCNA-positive staining were observed. In histologically normal cells, p53 staining was almost absent and PCNA-positive staining was regularly observed in the lower half of the crypt. In radiation colitis including aberrant glands, cellular proliferation increased and spotted p53 expression was observed. This study suggests that radiation colitis and aberrant glands might possess malignant potential and deeply associate with carcinogenesis of radiation-induced colon cancer. (author)

  2. ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

    Directory of Open Access Journals (Sweden)

    Giovanni Pallio

    2016-08-01

    Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  3. Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

    Science.gov (United States)

    Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

    2008-12-01

    The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

  4. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

    NARCIS (Netherlands)

    Bodin, J.; Kocbach Bølling, A.; Wendt, A.; Eliasson, L.; Becher, R.; Kuper, F.; Løvik, M.; Nygaard, U.C.

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese

  5. Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

    Science.gov (United States)

    Alagozlu, Hakan; Gorgul, Ahmet; Bilgihan, Ayse; Tuncer, Candan; Unal, Selahattin

    2013-02-01

    After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients

  6. Wasabia japonica is a potential functional food to prevent colitis via inhibiting the NF-κB signaling pathway.

    Science.gov (United States)

    Kang, Ju-Hee; Choi, Seungho; Jang, Jeong-Eun; Ramalingam, Prakash; Ko, Young Tag; Kim, Sun Yeou; Oh, Seung Hyun

    2017-08-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Many types of drugs are used to treat IBDs, but they exhibit adverse effects such as vomiting, nausea, abdominal pain, diarrhea, etc. In order to overcome the limitations of current therapeutic drugs, scientists have searched for functional foods from natural resources. In this study, we investigated the anti-colitic effects of Wasabia japonica extract in a DSS-induced colitis model. Wasabi japonica is a plant of the Brassicaceae family that has recently been reported to exhibit properties of detoxification, anti-inflammation, and induction of apoptosis in cancer cells. In this study, we generated wasabi ethanol extract (WK) and assessed its anti-colitic effect. In addition, in order to improve delivery of the extract to the colon, WK was coated with 5% Eudragit S100 (WKE), after which the anti-colitic effects of WKE were assessed. In conclusion, WK prevented development of colitis through inhibition of the NF-kB signaling pathway and recovery of epithelial tight junctions. In addition, the anti-colitic effect of WK was enhanced by improving its delivery to the colon by coating the WK with Eudragit S100. Therefore, we suggest that wasabi can be used as a new functional food to prevent IBDs due to its anti-colitic effect.

  7. Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

    DEFF Research Database (Denmark)

    Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen

    2015-01-01

    characterized the molecular phenotype of ulcerative colitis through transcriptomic and metabonomic profiling of colonic mucosal biopsies from patients and controls. We have characterized the extent to which metabonomic and transcriptomic molecular phenotypes are associated with ulcerative colitis versus...... transcriptomic and metabonomic data have previously been shown to predict the clinical course of ulcerative colitis and related clinical phenotypes, indicating that molecular phenotypes reveal molecular changes associated with the disease. Our analyses indicate that variables of both transcriptomics...... and metabonomics are associated with disease case and control status, that a large proportion of transcripts are associated with at least one metabolite in mucosal colonic biopsies, and that multiple pathways are connected to disease-related metabolites and transcripts....

  8. Cytomegalovirus colitis after systemic chemotherapy in a patient with recurrent colon cancer: A case report

    Directory of Open Access Journals (Sweden)

    Teraishi Fuminori

    2008-08-01

    Full Text Available Abstract Introduction The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. Case presentation We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. Conclusion The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

  9. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    OpenAIRE

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-01-01

    Abstract Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammat...

  10. Two cases of rectal cancer accompanied with radiation colitis

    International Nuclear Information System (INIS)

    Nakazaki, Takayuki; Tobinaga, Koji; Taketomi, Katsuro; Kimino, Koji; Nakasone, Tomonari; Kishikawa, Masao.

    1996-01-01

    This paper presents two cases of rectal cancer accompanied with radiation colitis. Case 1 was a 53-year-old woman, who had a history of undergoing radiation therapy for a uterine cervical cancer 11 years before. She was seen at the hospital because of constipation and pointed out a IIa-like lesion on the rectum by colonoscopy. Abdominoperineal resection was performed. The surgical specimen showed the IIa-like lesion on the rectum. Pathological findings revealed well-differentiated adenocarcinoma. Immunohistochemical staining of p53 showed positive cells in atrophic glands. Case 2 was a 62-year-old woman complaining of diarrhea. There was a previous history of receiving radiation therapy for a uterine cancer 20 years before. Colonoscopy showed a Borrmann type 2 cancer on the rectum. Abdominoperineal resection was performed. Histological findings revealed moderately differentiated adenocarcinoma invading to the propria muscle. The features of radiation colitis were observed around the cancer in the two cases which provided a clue to diagnose the lesions with radiation-induced cancer. (author)

  11. Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

    Science.gov (United States)

    2012-01-01

    Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. Results The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. Summary In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. Conclusion BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice. PMID

  12. Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

    Science.gov (United States)

    Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

    2012-10-22

    Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

  13. Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.

    Science.gov (United States)

    Berlec, Aleš; Perše, Martina; Ravnikar, Matjaž; Lunder, Mojca; Erman, Andreja; Cerar, Anton; Štrukelj, Borut

    2017-02-01

    TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Report of a case combining solitary Peutz-Jeghers polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon.

    Science.gov (United States)

    Papalampros, Alexandros; Vailas, Michail G; Sotiropoulou, Maria; Baili, Efstratia; Davakis, Spiridon; Moris, Demetrios; Felekouras, Evangelos; Deladetsima, Ioanna

    2017-10-18

    Colitis cystica profunda is a rare nonneoplastic disease defined by the presence of intramural cysts that contain mucus, usually situated in the rectosigmoid area, which can mimic various malignant lesions and polyps. Its etiology still remains not fully elucidated, and several mechanisms such as congenital, post-traumatic, and infectious have been implicated in the development of this rare entity. Herein, we describe a unique case of colitis cystica profunda in the setting of Peutz-Jeghers-type polyp of the sigmoid colon, associated with high-grade dysplasia of the overlying epithelium in a 48-year-old female patient, who presented to the emergency room with signs of intestinal obstruction. To the best of our insight, this is the first manifestation ever reported in the literature regarding the coexistence of solitary Peutz-Jeghers-type polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon. The purpose of this case report is to highlight colitis cystica profunda and its clinical significance. An uncommon nonneoplastic entity, many times masquerading as malignant lesion of the rectosigmoid area of the colon. Clinicians and pathologists should be aware of this benign condition that is found incidentally postoperatively in patients undergoing colectomies, leading to unnecessary increase of morbidity and mortality in these patients, who otherwise could have been cured with conservative treatment only.

  15. Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis.

    Science.gov (United States)

    Gong, Xiaohui; Xu, Xiaojuan; Lin, Sisi; Cheng, Yu; Tong, Jianhua; Li, Yongyu

    2017-08-01

    The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.

  16. Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

    Science.gov (United States)

    Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

    2017-08-01

    Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

    2017-01-01

    in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular...

  18. Lack of adrenomedullin results in microbiota changes and aggravates azoxymethane and dextran sulfate sodium-induced colitis in mice

    Directory of Open Access Journals (Sweden)

    Sonia Martinez-Herrero

    2016-11-01

    Full Text Available The link between intestinal inflammation, microbiota, and colorectal cancer (CRC is intriguing and the potential underlying mechanisms remain unknown. Here we evaluate the influence of adrenomedullin (AM in microbiota composition and its impact on colitis with an inducible knockout (KO mouse model for AM. Microbiota composition was analyzed in KO and wild type (WT mice by pyrosequencing. Colitis was induced in mice by administration of azoxymethane (AOM followed by dextran sulfate sodium (DSS in the drinking water. Colitis was evaluated using a clinical symptoms index, histopathological analyses, and qRT-PCR. Abrogation of the adm gene in the whole body was confirmed by PCR and qRT-PCR. KO mice exhibit significant changes in colonic microbiota: higher proportion of δ-Proteobacteria class; of Coriobacteriales order; and of other families and genera was observed in KO feces. Meanwhile these mice had a lower proportion of beneficial bacteria, such as Lactobacillus gasseri and Bifidobacterium choerinum. TLR4 gene expression was higher (p<0.05 in KO animals. AM deficient mice treated with DSS exhibited a significantly worse colitis with profound weight loss, severe diarrhea, rectal bleeding, colonic inflammation, edema, infiltration, crypt destruction, and higher levels of pro-inflammatory cytokines. No changes were observed in the expression levels of adhesion molecules. In conclusion, we have shown that lack of AM leads to changes in gut microbiota population and in a worsening of colitis conditions, suggesting that endogenous AM is a protective mediator in this pathology.

  19. A case of lanthanum carbonate ingestion thought to be phlebosclerotic colitis on CT imaging and abdominal radiograph

    International Nuclear Information System (INIS)

    Harris, K.; Balcam, S.

    2017-01-01

    A male admitted in the early hours of the morning, complained of a four week, right sided, non-radiating, dull and intermittent abdominal pain. Imaging suggested a diagnosis of phlebosclerotic colitis which was later discounted when the patients' history of lanthanum carbonate ingestion was examined. Phlebosclerotic colitis mostly affects the Asian population, and its cause is still not known, but can be associated with specific radiographic features. Collections of lanthanum may confuse a diagnosis of phlebosclerotic colitis as well as other factors such as voxel errors, photon starvation and movement. - Highlights: • PC can be non-specific, its cause unknown, diagnosis is often delayed. • PC depends on specific radiographic features. • Lanthanum Carbonate can collect within the lumen and confuses diagnosis. • Voxel errors, photon starvation and patient movement can displace densities.

  20. Management and treatment of distal ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Andrea Calafiore

    2013-12-01

    Full Text Available Ulcerative colitis (UC is a chronic inflammatory condition that is confined to the colonic mucosa. Its main symptoms include diarrhea, rectal bleeding and abdominal pain. Approximately two-thirds of UC patients have disease confined distal to the splenic flexure, which can be treated effectively with topical therapy. This means the active drug can be delivered directly to the site of inflammation, limiting the systemic absorption and potential side effects. Topical treatment with aminosalicylates is the most effective approach in the treatment of these forms, provided that the formulation reaches the upper margin of the disease. Given this, the suppository formulation is the treatment of choice for proctitis and distal sigmoiditis. Thanks to their proximal spread, enemas, foams and gels represent the treatment of choice for proctosigmoiditis and for distal ulcerative colitis. Oral aminosalicylates are less effective than topical therapies in patients with active disease, while the combination of topical and oral treatment is more effective in patients refractory to topical or oral mono-therapy. Topically administered aminosalicylates play an important role in the maintenance of remission, but the long-term adhesion to therapy is poor. For this reason, the oral formulation is the first-line therapy in the maintenance of remission. Refractory patients can be treated with topical steroids or systemic steroids and TNF-alpha inhibitors in severe forms.

  1. Celiac disease and other autoimmune diseases in patients with collagenous colitis.

    Science.gov (United States)

    Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

    2013-08-01

    Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

  2. Validation of the Persian version of the inflammatory bowel disease questionnaire (IBDQ) in ulcerative colitis patients.

    Science.gov (United States)

    Maleki, Iradj; Taghvaei, Tarang; Barzin, Maryam; Amin, Kamyar; Khalilian, Alireza

    2015-01-01

    Inflammatory bowel diseases (IBD) are a group of inflammatory conditions of the colon and small intestine that may have critical consequences on patient's quality of life (QOL). Many disease-specific QOL tools have been developed recently. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is one of them. The aim of this study was to translate the IBDQ from English to Persian and evaluate the validity and reliability of this version of the McMaster IBDQ. 68 subjects with ulcerative colitis were recruited in this study. The original IBDQ was translated into Persian using back- translation method. The reliability of the subscales and the summary score of the Persian IBDQ was demonstrated by intraclass correlation coefficients, their validity was evaluated by their correlations with SF-36, visual analogue scale and colitis activity index. All dimensions of IBDQ met the standards of construct validity and were correlated well with SF-36, visual analog scale and colitis activity index. IBDQ was able to discriminate the different groups of patients. The intraclass correlation coefficient was very high and its value was close to one (P<0.05). All dimensional scores differed significantly between the baseline and the follow-up measurement. The findings of this study conclude that the Persian translation of IBDQ confers satisfactory psychometric and cultural properties when applied to a sample of Iranian population with inflammatory bowel disease. This questionnaire is recommended for use in clinical trials and in the assessment of efficacy of interventions and therapy.

  3. Diversion procto-colitis: response to treatment with short-chain fatty acids.

    Science.gov (United States)

    Kiely, E M; Ajayi, N A; Wheeler, R A; Malone, M

    2001-10-01

    Diversion procto-colitis (DPC) results from a deficiency of luminal short-chain fatty acids (SCFAs). Endoscopic and histopathologic features of the disorder are almost universally present in defunctioned bowel, but symptomatic DPC is l