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Sample records for colitis collagenous colitis

  1. Collagenous colitis.

    PubMed Central

    Kingham, J G; Levison, D A; Morson, B C; Dawson, A M

    1986-01-01

    Clinical and pathological aspects of six patients with collagenous colitis are presented. These patients have been observed for between four and 15 years and the evolution of the condition is documented in three (cases 1, 3 and 5). Management and possible pathogenetic mechanisms of this enigmatic condition are discussed. Images Fig. 1 Fig. 2 PMID:3699567

  2. Collagenous colitis: an unrecognised entity.

    PubMed Central

    Bogomoletz, W V; Adnet, J J; Birembaut, P; Feydy, P; Dupont, P

    1980-01-01

    A patient is reported with chronic abdominal pain, diarrhoea, and associated radiological and endoscopic abnormalities of the sigmoid colon. Light and electron microscopic study of colorectal mucosa showed abnormal collagenous thickening of the subepithelial basement membrane. The authors felt that the clinical and morphological features justified a diagnosis of collagenous colitis. Review of the literature suggested that collagenous colitis was still an unrecognised entity. Images Fig. 1 Fig. 2 Fig. 3 PMID:7380341

  3. Colitis

    MedlinePlus

    ... those caused by a virus, parasite, and food poisoning due to bacteria Ulcerative colitis and Crohn disease Lack of blood flow (ischemic colitis) Past radiation to the large bowel Necrotizing enterocolitis in newborns ...

  4. Collagenous colitis: new diagnostic possibilities with endomicroscopy

    NASA Astrophysics Data System (ADS)

    Hoffman, A.; Goetz, M.; Biesterfeld, S.; Galle, P. R.; Neurath, M. F.; Kiesslich, R.

    2006-02-01

    Collagenous colitis is a kind of microscopic colitis. It is characterized by chronic watery diarrhea and abdominal pain. The etiology is still unknown. So far, for the diagnose a histological evaluation was necessary with the presence of thickened subepithelial collagneous bands in the lamina propria. A new developed endoscope with a confocal laser allows analysing cellular and subcellular details of the mucosal layer at high resolution in vivo. In this case report we describe for the first time to diagnose collagenous colitis during ongoing colonoscopy by using this confocal endomicroscopy. In a 67 year old female patient with typical symptoms the characteristic histological changes could be identified in the endomicroscopic view. Biopsies could be targeted to affected areas and endomicroscopic prediction of the presence of collagenous bands could be confirmed in all targeted biopsies. First endomicroscopic experience in microscopic colitis could be confirmed in four additional patients. Future prospective studies are warranted to further evaluate these initial findings. However, collagenous colitis is frequently missed and endomicroscopy seems to be the ideal tool for accurate diagnosing collagenous colitis during ongoing endoscopy.

  5. Autoantibodies and immunoglobulins in collagenous colitis.

    PubMed Central

    Bohr, J; Tysk, C; Yang, P; Danielsson, D; Järnerot, G

    1996-01-01

    BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined. RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls. CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis. PMID:8881813

  6. [Collagenous colitis. Morphologic and immunohistochemical study].

    PubMed

    Genova, G; Arena, N; Guddo, F; Vita, C; Reitano, R; Nagar, C; Tralongo, V

    1993-01-01

    Collagenous colitis is a clinico-pathological entity characterized by chronic diarrhoeas and deposition of collagen beneath the epithelium surface of large bowel. We revised 265 endoscopy biopsy specimens of the large bowel from 198 consecutive patients with "aspecific chronic colitis". Morphometric study showed that were not significant differences among various tracts in the same patients regarding to the thickness of basament membrane. It was more than 11.9 +/- 0.49 mu only in 13 pts (6.6%), while it was 3.96 +/- 1.4 mu in the others. Immunohistochemistry study confirmed the normality of subepithelial basement membrane and the below deposition of the large quantity of collagen IV.

  7. Review article: Microscopic colitis--lymphocytic, collagenous and 'mast cell' colitis.

    PubMed

    Yen, E F; Pardi, D S

    2011-07-01

    Microscopic colitis is a relatively common cause of chronic diarrhoea in predominantly older adults, traditionally termed lymphocytic colitis and collagenous colitis. Increased mast cells found in the colonic biopsies of some patients with chronic diarrhoea may represent a distinct type of microscopic colitis. To provide an updated review of the epidemiology, diagnosis and treatment of microscopic colitis, and to discuss the role of mast cells in the gastrointestinal tract and their potential role in cases of functional diarrhoea. A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. Incidence rates of microscopic colitis (lymphocytic and collagenous colitis) have increased over time, to levels comparable with other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis and concomitant coeliac sprue are important considerations when evaluating these patients. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. Mast cells have been implicated in functional bowel disorders, with increased mast cells possibly contributing to cases of otherwise unexplained chronic diarrhoea, although this concept requires further investigation. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. The role of mast cells in chronic diarrhoea represents an evolving field, with the potential to offer alternative treatment pathways in patients with otherwise unexplained functional diarrhoea. © 2011 Blackwell Publishing Ltd.

  8. Pseudomembranous Collagenous Colitis: A Case of Not-so-Microscopic Colitis

    PubMed Central

    Mehta, Manisha; Sheth, Sunil G.

    2016-01-01

    We present a 72-year-old male who developed progressive, watery diarrhea despite anti-motility agents. On colonoscopy, the mucosa was inflamed and covered with an exudate. Stool studies for Clostridium difficile and Escherichia coli were negative. Biopsies revealed pseudomembranous collagenous colitis, a rare form of microscopic colitis. His symptoms improved dramatically with budesonide therapy. PMID:28119938

  9. Microscopic colitis.

    PubMed

    Delgado, Jorge; Delgado, Bertha; Fich, Alex; Odes, Shmuel

    2004-08-01

    Microscopic colitis is an idiopathic chronic inflammatory bowel disease presenting with watery diarrhea. While colonoscopy and radiology findings are normal, the colon shows striking pathologic findings, including lymphocytic colitis and collagenous colitis. The clinical course is usually benign with sustained remission. Recent medical evidence shows that bismuth and budesonide are effective treatments.

  10. [Microscopic colitis].

    PubMed

    Bohr, Johan

    2002-02-11

    Microscopic colitis is an umbrella term for a newly described group of colitides, belonging to the inflammatory bowel diseases, which are only diagnosable by microscopic evaluation of a macroscopically normal colon mucosa. Collagenous colitis and lymphocytic colitis are the most common of these colitides. Microscopic colitis is characterised clinically by chronic non-bloody watery diarrhoea. Crampy abdominal pain, nocturnal diarrhoea, urgency, and initial weight loss are usual. Concomitant diseases of autoimmune origin and arthralgia are commonly seen. Treatment of microscopic colitis follows the guidelines for treatment of other inflammatory bowel diseases, but a substantial part of the patients with microscopic colitis enter spontaneous remission after some years. A minor part, however, have very troublesome symptoms and are almost refractory to treatment. Microscopic colitis has apparently no malignant potential.

  11. Optimal management of collagenous colitis: a review.

    PubMed

    O'Toole, Aoibhlinn

    2016-01-01

    Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC's natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications.

  12. Collagenous colitis associated with small intestinal villous atrophy.

    PubMed Central

    Hamilton, I; Sanders, S; Hopwood, D; Bouchier, I A

    1986-01-01

    Two patients diagnosed as having small intestinal hyperplastic villous atrophy and being treated with a gluten free diet were investigated because of persistent watery diarrhoea. Both were found to have collagenous colitis. Previous reports of this condition have emphasised the presence of normal small intestinal mucosal architecture and the association of collagenous colitis with intestinal villous atrophy has not previously been reported. Both cases responded to oral steroid therapy, but not to other previously recommended treatment regimens. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:3792923

  13. Proton pump inhibitor induced collagen expression in colonocytes is associated with collagenous colitis

    PubMed Central

    Mori, Shiori; Kadochi, Yui; Luo, Yi; Fujiwara-Tani, Rina; Nishiguchi, Yukiko; Kishi, Shingo; Fujii, Kiyomu; Ohmori, Hitoshi; Kuniyasu, Hiroki

    2017-01-01

    AIM To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined. METHODS Collagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR. In human materials, collagen expression was examined by immunohistochemistry. RESULTS CT26 cells expressed a Na+-H+ exchanger gene (solute carrier family 9, member A2). Treatment with PPI and/or PPI-induced alkaline media caused growth inhibition and oxidative stress in CT26 cells. The treatment increased expression of fibrosis inducing factors, transforming growth factor β and fibroblast growth factor 2. The treatment also decreased expression of a negative regulator of collagen production, replication factor C1, resulting in increased expression of collagen types III and IV in association with lipid peroxide. In biopsy specimens from patients with collagenous colitis, type III and IV collagen were increased. Increase of type III collagen was more pronounced in PPI-associated collagenous colitis than in non-PPI-associated disease. CONCLUSION From these findings, the reaction of colonocytes to PPI might participate in pathogenesis of collagenous colitis. PMID:28321159

  14. Microscopic colitis

    PubMed Central

    Ianiro, Gianluca; Cammarota, Giovanni; Valerio, Luca; Annicchiarico, Brigida Eleonora; Milani, Alessandro; Siciliano, Massimo; Gasbarrini, Antonio

    2012-01-01

    Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data. PMID:23180940

  15. Microscopic colitis.

    PubMed

    Ianiro, Gianluca; Cammarota, Giovanni; Valerio, Luca; Annicchiarico, Brigida Eleonora; Milani, Alessandro; Siciliano, Massimo; Gasbarrini, Antonio

    2012-11-21

    Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.

  16. Ulcerative Colitis

    MedlinePlus

    Ulcerative colitis Overview By Mayo Clinic Staff Ulcerative colitis (UL-sur-uh-tiv koe-LIE-tis) is an inflammatory ... and ulcers (sores) in your digestive tract. Ulcerative colitis affects the innermost lining of your large intestine ( ...

  17. Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis.

    PubMed

    Mellander, Marie-Rose; Ekbom, Anders; Hultcrantz, Rolf; Löfberg, Robert; Öst, Åke; Björk, Jan

    2016-01-01

    Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC). A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled. Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p = 0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p = 0.0014), and nocturnal diarrhoea in 28% versus 18% (p = 0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p = 0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients. Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation 'microscopic'. Our study confirms the strong association with coeliac disease.

  18. Pseudomembranous Colitis

    PubMed Central

    Farooq, Priya D.; Urrunaga, Nathalie H.; Tang, Derek M.; von Rosenvinge, Erik C.

    2015-01-01

    Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms persist despite escalating empiric treatment, early gastroenterology consultation and lower endoscopy would be the next step in the appropriate clinical setting. If pseudomembranous colitis is confirmed endoscopically, colonic biopsies should be obtained, as histology can offer helpful clues to the underlying diagnosis. The less common non-C. difficile causes of pseudomembranous colitis should be entertained, as a number of etiologies can result in this condition. Examples include Behcet’s disease, collagenous colitis, inflammatory bowel disease, ischemic colitis, other infections organisms (e.g. bacteria, parasites, viruses), and a handful of drugs and toxins. Pinpointing the correct underlying etiology would better direct patient care and disease management. Surgical specialists would be most helpful in colonic perforation, gangrenous colon, or severe disease. PMID:25769243

  19. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice.

    PubMed

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry; Moulin, David

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between "colitis" and "arthritis+colitis" groups during colitis development. Interestingly a milder decrease of bacterial diversity in the "arthritis+colitis" group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.

  20. A unique case of collagenous colitis presenting as protein-losing enteropathy successfully treated with prednisolone

    PubMed Central

    Sano, Soichi; Yamagami, Keiko; Tanaka, Ayako; Nishio, Minako; Nakamura, Tomoyuki; Kubo, Yuki; Inoue, Takeshi; Ueda, Wataru; Okawa, Kiyotaka; Yoshioka, Katsunobu

    2008-01-01

    A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa, and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon, particularly in the ascending portion, was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy (PLE) without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management. PMID:18932290

  1. Microscopic colitis: a review.

    PubMed

    Farrukh, A; Mayberry, J F

    2014-12-01

    In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70 years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  2. [Microscopic colitis: update 2014].

    PubMed

    Burgmann, Konstantin; Fraga, Montserrat; Schoepfer, Alain M; Yun, Pu

    2014-09-03

    Microscopic colitis, which includes lymphocytic colitis and collagenous colitis, represents a frequent cause of chronic watery diarrhea especially in the elderly population. Several medications, such as nonsteroidal antiinflammatory drugs, proton pump inhibitors or antidepressants, as well as cigarette smoking have been recognized as risk factors for microscopic colitis. The diagnosis of microscopic colitis is based on a macroscopically normal ileo-colonoscopy and several biopsies from the entire colon, which demonstrate the pathognomonic histopathologic findings. Therapy is mainly based on the use of budesonide. Other medications, such as mesalazine, cholestyramine and bismuth, have been evaluated as well but the evidence is less solid.

  3. Smoking Status Influences Clinical Outcome in Collagenous Colitis.

    PubMed

    Münch, Andreas; Tysk, Curt; Bohr, Johan; Madisch, Ahmed; Bonderup, Ole K; Mohrbacher, Ralf; Mueller, Ralph; Greinwald, Roland; Ström, Magnus; Miehlke, Stephan

    2016-04-01

    The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known. In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model. Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome. Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

  4. Automated image analysis in the study of collagenous colitis

    PubMed Central

    Fiehn, Anne-Marie Kanstrup; Kristensson, Martin; Engel, Ulla; Munck, Lars Kristian; Holck, Susanne; Engel, Peter Johan Heiberg

    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. Twenty-five cases were primarily diagnosed as CC, 25 as CCi, and 25 as normal or near-normal colonic mucosa. Four pathologists individually reassessed the biopsies and categorized all into one of the abovementioned three categories. The result of the VG app was correlated with the diagnosis provided by the four pathologists. Results The interobserver agreement for each pair of pathologists ranged from κ-values of 0.56–0.81, while the κ-value for the VG app vs each of the pathologists varied from 0.63 to 0.79. The overall agreement between the four pathologists was κ=0.69, while the overall agreement between the four pathologists and the VG app was κ=0.71. Conclusion In conclusion, the Visiopharm VG app is able to measure the thickness of a sub-epithelial collagenous band in colon biopsies with an accuracy comparable to the performance of a pathologist and thereby provides a promising supplementary tool for the diagnosis of CC and CCi and in particular for research. PMID:27114713

  5. Collagenous colitis and collagenous gastritis in a 9 year old girl: a case report and review of the literature.

    PubMed

    Camarero Salces, C; Enes Romero, P; Redondo, C; Rizo Pascual, J M; Roy Ariño, G

    2011-09-01

    Collagenous gastritis is a rare disease in the general population and collagenous colitis has seldom been reported in children. We report a girl with both diseases and review the literature on this association afetr a systematic search of Pubmed, Medline and Embase databases.. The girl, diagnosed of collagenous colitis at the age of 2 years, started with abdominal pain and anaemia at the age of 9 years and was diagnosed of collagenous gastritis in the gastric biopsies. After review of the literature, we found 66 reported cases (33 children, 33 adults, 68% females), 56 patients with collagenous gastritis and 16 children with collagenous colitis. Both disorders coexisted in 20 patients. The main presenting symptoms are abdominal pain and anaemia in patients with collagenous gastritis and diarrhoea and weight loss in patients with both disorders. Hypoalbuminemia was found in 9 patients with both diseases and protein losing enteropathy was demonstrated in 3 cases. Deposits of collagen in the duodenum were observed in 13 of 19 patients with both diseases. Seventeen of 66 patients had associated autoimmune disorders, particularly in patients with both diseases (35%). These conditions have a chronic course but gastric or colonic malignancies have not been communicated to date. In conclusion, collagenous gastritis and collagenous colitis mainly affects women and can occur at any age. Their association is exceptional. These disorders, although rare, should be considered in patients with anaemia and epigastric pain, watery diarrhoea or protein losing enteropathy.

  6. Ulcerative colitis

    MedlinePlus

    ... proctocolectomy - discharge Types of ileostomy Ulcerative colitis - discharge Review Date 8/14/2015 Updated by: Subodh K. ... gastroenterologist at Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Internal review and ...

  7. Ulcerative Colitis

    MedlinePlus

    ... become very limited, talk to a registered dietitian. Stress Although stress doesn't cause inflammatory bowel disease, ... al. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. American Journal of ...

  8. Activation of nuclear factor κB in colonic mucosa from patients with collagenous and ulcerative colitis

    PubMed Central

    Andresen, L; Jørgensen, V L; Perner, A; Hansen, A; Eugen-Olsen, J; Rask-Madsen, J

    2005-01-01

    Background and aims: Expression of inducible nitric oxide synthase (iNOS) is greatly upregulated in the colonic mucosa of patients with collagenous and ulcerative colitis. As the transcription factor nuclear factor κB (NFκB) is a major inducer of iNOS gene expression, we compared activation and transcriptional activity of NFκB in colonic mucosal biopsies from these patients. Patients: Eight patients with collagenous colitis, six with relapsing ulcerative colitis, and eight with uninflamed bowel were studied. Methods: NFκB DNA binding activity was assessed by electrophoretic mobility shift assay and inhibitor of NFκB (IκB) kinase (IKK) activity by immunocomplex kinase assay. In vivo recruitment of NFκB to the iNOS promoter was determined by chromatin immunoprecipitation analysis and transcriptional activity by NFκB gene expression profiling arrays. Cells showing NFκB activation were identified by immunohistochemistry. Results: In collagenous and ulcerative colitis, as opposed to uninflamed bowel, IKKβ activity and strong NFκB DNA binding gave rise to activation of identical NFκB subunits and recruitment of transcriptionally active p65 to the iNOS promoter. In collagenous colitis, activated NFκB was observed only in epithelial cells while up to 10% of lamina propria macrophages showed activation in ulcerative colitis. Conclusions: In collagenous and ulcerative colitis, colonic mucosal NFκB is activated and recruited to the iNOS promoter in vivo via an IKKβ mediated pathway. As collagenous colitis is not associated with tissue injury, these data challenge the prevailing view that activation of NFκB per se mediates tissue injury. Our results suggest that downstream inflammatory reactions leading to tissue damage originate in lamina propria immune cells, as increased NFκB activity in collagenous colitis was localised solely in epithelial cells, but present also in macrophages in ulcerative colitis. PMID:15753535

  9. Ischemic Colitis

    PubMed Central

    Montessori, Gino; Liepa, Egils V.

    1970-01-01

    Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9 PMID:5308923

  10. CMV - gastroenteritis/colitis

    MedlinePlus

    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  11. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  12. Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report

    PubMed Central

    Daferera, Niki; Kumawat, Ashok Kumar; Hultgren-Hörnquist, Elisabeth; Ignatova, Simone; Ström, Magnus; Münch, Andreas

    2015-01-01

    In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis. PMID:26019474

  13. Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis.

    PubMed

    Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan

    2017-02-21

    One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC.

  14. Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis

    PubMed Central

    Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan

    2017-01-01

    One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC. PMID:28275312

  15. Celiac disease and other autoimmune diseases in patients with collagenous colitis.

    PubMed

    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.

  16. Ulcerative Colitis.

    PubMed

    Sonnenberg, Elena; Siegmund, Britta

    2016-01-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is chronically present in patients throughout their lives. Hence, the chronic nature of the disease invariably requires continuous medical treatment. Advances in medical therapy over the last decades and current developments offer increasing options and are closely associated with a better life quality in patients. Recent developments in understanding the pathogenesis of UC are discussed. The current standard therapeutic regimens are outlined and recent developments and upcoming strategies introduced. (1) Environmental factors that are yet to be defined contribute to the pathogenesis of UC. (2) An accelerated step-up therapy represents the current standard in UC. (3) Anti-integrins represent the most recently introduced pharmacological class in the therapy of UC. (4) Novel strategies including Janus kinase inhibitors are in the near future. © 2016 S. Karger AG, Basel.

  17. Eosinophilic colitis

    PubMed Central

    Okpara, Nnenna; Aswad, Bassam; Baffy, Gyorgy

    2009-01-01

    Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions, inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination. Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics. PMID:19554649

  18. Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE).

    PubMed

    Rönnblom, Anders; Holmström, Tommy; Tanghöj, Hans; Wanders, Alkwin; Sjöberg, Daniel

    2015-01-01

    Inflammatory bowel disease (IBD), microscopic colitis and celiac disease are all diseases with worldwide distribution and increased incidence has been reported from many areas. There is a shortage of studies investigating the occurrence of these diseases in the same individual and whether those affected demonstrate any particular phenotype. The aim of the study was to describe the concomitant incidence of microscopic colitis and celiac disease in a population-based IBD cohort. All 790 individuals in a prospective population-based cohort included 2005-09 from Uppsala region, Sweden, were reviewed regarding the appearance of microscopic or celiac disease before or after IBD diagnosis. Fifty percent (396/790) of the patients had been examined for the possibility of celiac disease. Seventeen patients with celiac disease were found, representing 2.2% of the cohort. Patients with celiac disease were younger compared to the non-celiac patients and those with colitis had more often an extensive inflammation of the colon. Seventy-one percent (12/17) were women. The majority of the patients were diagnosed with celiac disease before IBD. Five patients with IBD had an earlier diagnosis of microscopic colitis or developed it after the IBD diagnosis. One teenager developed collagenous sprue, misinterpreted as a severe relapse of ulcerative colitis (UC) resulting in colectomy. The risk for celiac disease seems not to be increased in IBD, but those affected by both diseases seem to be predominantly women with extensive UC. There is a potential association between microscopic colitis and IBD.

  19. Mucosa-associated bacteria in two middle-aged women diagnosed with collagenous colitis

    PubMed Central

    Gustafsson, Rita J; Ohlsson, Bodil; Benoni, Cecilia; Jeppsson, Bengt; Olsson, Crister

    2012-01-01

    AIM: To characterize the colon microbiota in two women histologically diagnosed with collagenous colitis using a culture-independent method. METHODS: Biopsies were taken from the ascending colon and the total DNA was extracted. Universal bacterial primers were used to amplify the bacterial 16S rRNA genes. The amplicons were then cloned into competent Escherichia coli cells. The clones were sequenced and identified by comparison to known sequences. RESULTS: The clones could be divided into 44 different phylotypes. The microbiota was dominated by Firmicutes and Bacteroidetes. Seven phylotypes were found in both patients and constituted 47.5% of the total number of clones. Of these, the most dominating were clones similar to Bacteroides cellulosilyticus, Bacteroides caccae, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides dorei within Bacteroidetes. Sequences similar to Faecalibacterium prausnitzii and Clostridium citroniae were also found in both patients. CONCLUSION: A predominance of potentially pathogenic Bacteroides spp., and the presence of clones showing similarity to Clostridium clostridioforme were found but the overall colon microbiota showed similarities to a healthy one. Etiologies for collagenous colitis other than an adverse bacterial flora must also be considered. PMID:22529692

  20. The synthetic hydroxyproline-containing collagen analogue (Gly-Pro-Hyp)10 ameliorates acute DSS colitis.

    PubMed

    Heimesaat, M M; Heilmann, K; Kühl, A A; Erben, U; Rühl, M; Fischer, A; Farndale, R W; Bereswill, S; Göbel, U B; Zeitz, M; Somasundaram, R; Freise, C

    2012-09-01

    In experimental models of and humans with intestinal inflammation, increased levels of the matrix-degrading gelatinases MMP-2 and -9 in inflamed tissues can be detected. The synthetic collagen analogue (Gly-Pro-Hyp)10, (GPO)10, has been identified as a relevant binding structure for proMMP-2/-9 and promotes enzymatic activity of proMMP-2. Since targeted MMP strategies might offer promising anti-inflammatory treatment options, we for the first time studied in vivo actions exerted by (GPO)10 applying an acute dextrane sulfate sodium (DSS) induced colitis model. Seven-day intraperitoneal (GPO)10 treatment ameliorated clinical symptoms and histopathological colonic changes as compared to placebo controls with severe colitis. (GPO)10-treated mice displayed a diminished influx of neutrophils, and T- and B-lymphocytes into their colonic mucosa whereas numbers of regulatory T-cells and regenerative cells were higher as compared to placebo controls. Furthermore, IL-6 secretion was down-regulated in ex vivo colonic biopsies derived from (GPO)10-treated mice whereas higher concentrations of the anti-inflammatory cytokine IL-10 in extra-intestinal compartments such as MLN and spleen could be detected. Strikingly, influx of inflammatory cells into lungs was abolished following (GPO)10 application. We therefore propose (GPO)10 as a promising effective and safe treatment option of intestinal and extra-intestinal inflammatory conditions in humans.

  1. The synthetic hydroxyproline-containing collagen analogue (Gly–Pro–Hyp)10 ameliorates acute DSS colitis

    PubMed Central

    Heimesaat, M. M.; Heilmann, K.; Kühl, A. A.; Erben, U.; Rühl, M.; Fischer, A.; Farndale, R. W.; Bereswill, S.; Göbel, U. B.; Zeitz, M.; Somasundaram, R.; Freise, C.

    2012-01-01

    In experimental models of and humans with intestinal inflammation, increased levels of the matrix-degrading gelatinases MMP-2 and -9 in inflamed tissues can be detected. The synthetic collagen analogue (Gly–Pro–Hyp)10, (GPO)10, has been identified as a relevant binding structure for proMMP-2/-9 and promotes enzymatic activity of proMMP-2. Since targeted MMP strategies might offer promising anti-inflammatory treatment options, we for the first time studied in vivo actions exerted by (GPO)10 applying an acute dextrane sulfate sodium (DSS) induced colitis model. Seven-day intraperitoneal (GPO)10 treatment ameliorated clinical symptoms and histopathological colonic changes as compared to placebo controls with severe colitis. (GPO)10-treated mice displayed a diminished influx of neutrophils, and T- and B-lymphocytes into their colonic mucosa whereas numbers of regulatory T-cells and regenerative cells were higher as compared to placebo controls. Furthermore, IL-6 secretion was down-regulated in ex vivo colonic biopsies derived from (GPO)10-treated mice whereas higher concentrations of the anti-inflammatory cytokine IL-10 in extra-intestinal compartments such as MLN and spleen could be detected. Strikingly, influx of inflammatory cells into lungs was abolished following (GPO)10 application. We therefore propose (GPO)10 as a promising effective and safe treatment option of intestinal and extra-intestinal inflammatory conditions in humans. PMID:24688765

  2. Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis

    PubMed Central

    Perner, A; Andresen, L; Normark, M; Fischer-Hansen, B; Sorensen, S; Eugen-Olsen, J; Rask-Madsen, J

    2001-01-01

    BACKGROUND AND AIMS—Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In addition, effects on colonic fluid transfer caused by manipulating the substrate of NOS were studied in patients with collagenous colitis.
PATIENTS—Eight patients with collagenous colitis, nine with active ulcerative colitis, and 10 with uninflamed bowel were included.
METHODS—Expression of NOS isoforms was quantified by western blotting. Inducible NOS (iNOS) and nitrotyrosine were localised by immunohistochemistry. Modulation of NOS activity by topical NG-monomethyl-L-arginine (L-NMMA) or L-arginine was assessed during perfusion of whole colon. Plasma and perfusate nitrite/nitrate (NOx) was measured by Griess' reaction.
RESULTS—Both in collagenous and ulcerative colitis, expression of iNOS was 102-103 higher (p<0.001) than in uninflamed bowel and localised primarily to the epithelium. Endothelial NOS was evenly expressed in all groups while neuronal NOS was undetectable. Nitrotyrosine was markedly expressed in active ulcerative colitis but rarely detected in collagenous colitis and never in uninflamed bowel. In collagenous colitis, the output of NOx was markedly increased compared with uninflamed bowel (283 (58) v <37 nmol/min; p<0.01) and fluid was net secreted. L-NMMA reduced the output of NOx by 13-66% (95% confidence intervals) and secretion of fluid by 25-109% whereas L-arginine increased the output of NOx by 3-39% and secretion of fluid by 15-93%.
CONCLUSIONS—In collagenous colitis, as opposed to ulcerative colitis, upregulation of iNOS occurs in the absence of nitrotyrosine formation and mucosal damage. Excess generation of NO may be the primary cause of diarrhoea in this condition.


Keywords: colitis; ulcerative colitis

  3. Preparation and evaluation of mesalamine collagen in situ rectal gel: a novel therapeutic approach for treating ulcerative colitis.

    PubMed

    Ramadass, Satiesh Kumar; Perumal, Sathiamurthi; Jabaris, Sugin Lal; Madhan, Balaraman

    2013-01-23

    Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects the colonic mucosa. Mesalamine had been established as a first line drug for treating mild to moderate UC. A continued availability of the drug for treatment of damaged tissues remains a great challenge today. In the present study, a novel mesalamine collagen in situ gel has been prepared using type I collagen, which is pH/temperature sensitive. This hydrogel undergoes sol-gel transition under physiological pH and temperature which was confirmed by rheological studies. The in vitro release profile demonstrated sustained release of mesalamine over a period of 12h. The in vivo efficacy of the in situ gel was performed using dextran sodium sulphate induced ulcerative colitis model in BALB/c mice. The clinical parameters such as, body weight changes, rectal bleeding and stool consistency were evaluated. In addition, the histopathological investigation was conducted to assess severity of mucosal damage and inflammation infiltrate. There was a significant reduction in rectal bleeding and mucosal damage score for collagen-mesalamine in situ gel group compared to the reference group. Apart from releasing mesalamine in controlled manner, the strategy of administering mesalamine through collagen in situ gel facilitates regeneration of damaged mucosa resulting in a synergistic effect for the treatment of ulcerative colitis.

  4. [Case of suspicious lansoprazole-associated collagenous colitis in ANCA-associated nephritis].

    PubMed

    Sasatomi, Yoshie; Takahata, Masafumi; Abe, Yasuhiro; Ishimura, Atsunori; Miyake, Katsuhisa; Ogahara, Satoru; Murata, Toshiaki; Nakashima, Hitoshi; Maeda, Kazuhiro; Saito, Takao

    2010-01-01

    . The symptoms disappeared within 5 days. There have been few reports of collagenous colitis with chronic diarrhea, but a good prognosis has been described in these cases. Clinicians should consider drug treatment as a possible cause of collagenous colitis in the case of patients with chronic diarrhea of unknown origin during the administration of medication.

  5. Cytokine expression of microscopic colitis including interleukin-17.

    PubMed

    Park, Eun-Kyoung; Park, Young Sook; Park, Dae Rim; Jung, Sung Ae; Han, Dong Soo; Jang, Byung Ik; Kim, Young Ho; Kim, Won Ho; Jo, Yun Ju; Lee, Ki Ho; Lee, Won Mi; Kim, Eun Kyung; Koo, Hae Soo

    2015-05-23

    Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis. This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunohistochemical analysis of the colonic mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, interferon-γ, inducible nitric oxide synthase, and tumor necrosis factor-α. We compared the quantity score of immunohistochemical staining among the groups. The microscopic colitis group showed significantly higher expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, and interferon-γ compared with the control group. Cytokine expression was similar between collagenous colitis and lymphocytic colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous colitis. Proinflammatory cytokines, including interleukin-17 and interferon-γ, are highly expressed in microscopic colitis. The expression of cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis. This study is the first on interleukin-17 expression in microscopic colitis patients.

  6. Ulcerative colitis - discharge

    MedlinePlus

    ... lose weight or your diet becomes very limited. Stress You may feel worried about having a bowel ... DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol . ...

  7. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  8. Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: A new treatment strategy.

    PubMed

    Ramadass, Satiesh Kumar; Jabaris, Sugin Lal; Perumal, Ramesh Kannan; HairulIslam, Villianur Ibrahim; Gopinath, Arun; Madhan, Balaraman

    2016-08-25

    Ulcerative colitis, particularly the chronic persistent form is characterized by the presence of active inflammation and extensive areas of ulceration in the colonic mucosa. The existing treatment protocol aims at only reducing intestinal inflammation, rather than targeting mucosal ulceration. In this study, type I collagen and its daughter peptides called collagen hydrolysate, highly popular reconstructive materials for tissue engineering applications, are hypothesized as healing matrices to target the recuperation of internal mucosal ulceration. The clinical assessments on day 10 of dextran sodium sulfate induced colitis in mice model revealed that both the collagen (1.56±0.29) and collagen hydrolysate treatments (1.33±0.33) showed a significant reduction in the rectal bleeding compared to the reference mesalamine treatment (2.50±0.33) and untreated negative control (2.40±0.40). VEGF, a potent angiogenic growth factor, over expressed during UC was down-regulated by collagen hydrolysate (1.06±0.25) and collagen (1.76±0.45) to a greater extent than by mesalamine (2.59±0.51) and untreated control (4.17±0.15). The down-regulation of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 also follows the same pattern. Histological observations were in accordance with the clinical indicators. Both collagen and collagen hydrolysate treatments showed significant reduction in mucosal damage score and facilitated faster regeneration of damaged mucosa. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Sustained Release Myofascial Release as Treatment for a Patient with Complications of Rheumatoid Arthritis and Collagenous Colitis: A Case Report

    PubMed Central

    Cubick, Erin E.; Quezada, Vanessa Y.; Schumer, Ariel D.; Davis, Carol M.

    2011-01-01

    Background: Myofascial release (MFR) is a manual therapeutic technique used to release fascial restrictions, which may cause neuromusculoskeletal and systemic pathology. Purpose: This case report describes the use of sustained release MFR techniques in a patient with a primary diagnosis of rheumatoid arthritis (RA) and a secondary diagnosis of collagenous colitis. Changes in pain, cervical range of motion, fatigue, and gastrointestinal tract function, as well as the impact of RA on daily activities, were assessed. Methods: A 54-year-old white woman presented with signs and symptoms attributed to RA and collagenous colitis. Pre and post measurements were taken with each treatment and during the interim between the initial and final treatment series. The patient recorded changes in pain, fatigue, gastrointestinal tract function, and quality of life. Cervical range of motion was assessed. Six sustained release MFR treatment sessions were provided over a 2-week period. Following an 8-week interim, two more treatments were performed. Results: The patient showed improvements in pain, fatigue, gastrointestinal tract function, cervical range of motion, and quality of life following the initial treatment series of six sessions. The patient maintained positive gains for 5 weeks following the final treatment, after which her symptoms returned to near baseline measurements. Following two more treatments, positive gains were achieved once again. Conclusions: In a patient with RA and collagenous colitis, the application of sustained release MFR techniques in addition to standard medical treatment may provide short-term and long-term improvements in comorbid symptoms and overall quality of life. PMID:22016756

  10. Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

    PubMed

    Fernandez-Bañares, Fernando; Piqueras, Marta; Guagnozzi, Danila; Robles, Virginia; Ruiz-Cerulla, Alexandra; Casanova, María José; Gisbert, Javier P; Busquets, David; Arguedas, Yolanda; Pérez-Aisa, Angeles; Fernández-Salazar, Luis; Lucendo, Alfredo J

    2017-09-01

    Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. Cytomegalovirus Colitis in Immunocompetent Patients

    PubMed Central

    Hussain, Qulsoom; Shafique, Khurram; Tasleem, Syed H; Hurairah, Abu

    2016-01-01

    Cytomegalovirus colitis is common in immunocompromised patients, but rare in immunocompetent patients. The present study not only represents the colonoscopy and pathological findings, but also applies the method of diagnosing and treating cytomegalovirus colitis in immunocompetent patients. PMID:27980888

  12. Microscopic colitis: A literature review.

    PubMed

    Clara, Ana Paula Hamer Sousa; Magnago, Flávia Drago; Ferreira, Juliana Neves; Grillo, Thais Gagno

    2016-12-01

    Microscopic colitis (MC) refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD), which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords "microscopic colitis", "collagenous colitis", "lymphocytic colitis", and "review" for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.

  13. Contemporary methods for the diagnosis and treatment of microscopic colitis.

    PubMed

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Geboes, Karel

    2016-01-01

    Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.

  14. Antimicrobial Peptides and Colitis

    PubMed Central

    Ho, Samantha; Pothoulakis, Charalabos; Koon, Hon Wai

    2013-01-01

    Antimicrobial peptides (AMPs) are important components of innate immunity. They are often expressed in response to colonic inflammation and infection. Over the last several years, the roles of several antimicrobial peptides have been explored. Gene expression of many AMPs (beta defensin HBD2-4 and cathelicidin) is induced in response to invasion of gut microbes into the mucosal barrier. Some AMPs are expressed in a constitutive manner (alpha defensin HD 5-6 and beta defensin HBD1), while others (defensin and bactericidal/permeability increasing protein BPI) are particularly associated with Inflammatory Bowel Disease (IBD) due to altered defensin expression or development of autoantibodies against Bactericidal/permeability increasing protein (BPI). Various AMPs have different spectrum and strength of antimicrobial effects. Some may play important roles in modulating the colitis (cathelicidin) while others (lactoferrin, hepcidin) may represent biomarkers of disease activity. The use of AMPs for therapeutic purposes is still at an early stage of development. A few natural AMPs were shown to be able to modulate colitis when delivered intravenously or intracolonically (cathelicidin, elafin and SLPI) in mouse colitis models. New AMPs (synthetic or artificial non-human peptides) are being developed and may represent new therapeutic approaches against colitis. This review discusses the latest research developments in the AMP field with emphasis in innate immunity and pathophysiology of colitis. PMID:22950497

  15. Eosinophilic colitis in children

    PubMed Central

    Horowska-Ziaja, Sabina; Kajor, Maciej; Więcek, Sabina; Chlebowczyk, Wojciech; Woś, Halina

    2017-01-01

    Introduction Eosinophilic colitis, which is a rare form of eosinophilic gastrointestinal diseases, occurs as primary and secondary allergic eosinophilic colitis of the gastrointestinal tract infection, inflammatory bowel disease, celiac disease, and vasculitis. The diagnosis is based on a significant amount of eosinophils in the inflammatory infiltrate of the colon wall. Aim To analyze the clinical picture taking into account comorbidities and endoscopic picture in children with eosinophilic colitis. Material and methods The test group consisted of 43 children, the average age – 12.1 years diagnosed with eosinophilic colitis (according to the Whitington scale) hospitalized in the Gastroenterology Unit, Department of Pediatrics of the Medical University of Silesia in Katowice. Testing for food allergies, celiac disease, inflammatory bowel disease, gastrointestinal diseases and parasitic diseases was performed in the group of children and the analysis concerned the intensity of eosinophilic infiltration of the colon mucosa with the severity of clinical symptoms, endoscopic picture, the presence of inflammatory bowel disease, and food allergy. Results Half of the tested children suffered from isolated eosinophilic colitis but the rest of them had eosinophilic infiltrate with inflammatory bowel disease more often, however, the Crohn’s disease. The endoscopic image was uncharacteristic, and grade III in the Whitington scale was predominant in the histopathological examination, in most cases located in the entire large intestine. The higher level of total IgE was found in less than half of the patients and it did not correlate with the severity of eosinophilic infiltration. It was shown that the severity of eosinophilic infiltration correlated with exacerbation of clinical symptoms, endoscopic image, and the presence of inflammatory bowel disease. The higher level of antibodies of ASCA and ANCA was found in approximately 20% of the children with isolated eosinophilic

  16. Peanut shell colitis.

    PubMed

    Keeffe, E B; Girard, D E

    1985-07-01

    A 40-year-old physician experienced abdominal pain, loose stools, hematochezia, and anal discomfort with defecation associated with the daily consumption of 15 to 30 whole peanuts, including the shells. Thorough evaluation revealed only nonspecific colitis of the distal portion of the sigmoid colon and inflamed hemorrhoids. Discontinuation of whole peanut ingestion was associated with symptomatic, endoscopic, and histological resolution. In this patient, undigested peanut shells seem to have caused a nonspecific colitis, perhaps as the result of mechanical abrasion of the colonic mucosa.

  17. Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis

    MedlinePlus

    ... not need anesthesia. Health care providers use imaging tests to show physical abnormalities and to diagnose certain bowel diseases, in some cases. CT scan. CT scans use a combination of x rays and computer technology to create images. For a CT scan, a ...

  18. Microscopic Colitis: What Do We Know About Pathogenesis?

    PubMed

    Pisani, Laura Francesca; Tontini, Gian Eugenio; Vecchi, Maurizio; Pastorelli, Luca

    2016-02-01

    Microscopic colitis (MC) is a common cause of chronic diarrhea. The 2 most frequent forms of MC are collagenous colitis and lymphocytic colitis. Over the past years, the incidence and prevalence of microscopic colitis are rising and this is largely attributed to a greater awareness, and concomitantly an increasing number of diagnoses. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. The underlying mechanisms involved in the pathogenesis of microscopic colitis remain unspecified but is probably multifactorial. Collagenous colitis and lymphocytic colitis may represent specific mucosal responses to different luminal agents in predisposed individuals, resulting in an uncontrolled immune response. Genetic predisposition, altered modulation of cytokines and miRNAs, and aberrant response to drugs seem to be involved in the development of MC. Despite the progress of knowledge, still many questions remain unsolved regarding the etiology, pathophysiology, and optimal management of MC. This review gives an update on the immunological aspects of collagenous colitis and lymphocytic colitis.

  19. Diagnosis and treatment of microscopic colitis.

    PubMed

    Okamoto, Ryuichi; Negi, Mariko; Tomii, Syohei; Eishi, Yoshinobu; Watanabe, Mamoru

    2016-08-01

    Microscopic colitis (MC) designates two types of chronic diarrhea diseases, which are lymphocytic colitis and collagenous colitis. The prevalence of microscopic colitis is increasing in both Western and Eastern countries, possibly due to the high incidence of colonoscopic survey in chronic diarrhea patients. Although the overall prognosis of MC patients is mostly good, it should be noted that appropriate diagnosis and choice of treatment is required to assure a good clinical outcome for MC patients. Also, a certain population of MC patients may take a severe and refractory clinical course, and thus require advanced clinical care using medications supported by less evidence. In this review, we would like to feature the essential points regarding the diagnosis of MC, and also describe the current standard of treatments for MC patients. In addition, we would like to add some findings from the national survey and research carried out in Japan, to compare those data with the western countries.

  20. Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

    PubMed Central

    Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

    2016-01-01

    Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http

  1. Eosinophilic colitis in infants.

    PubMed

    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.

  2. Pseudomembranous colitis in cystic fibrosis.

    PubMed

    Nagakumar, Prasad

    2013-05-01

    Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  4. [A clinical study of fulminant amebic colitis].

    PubMed

    Mori, Yoshihiro; Shimizu, Sadatoshi; Nishiguchi, Yukio; Ishii, Naomi; Inoue, Takeshi; Yamamoto, Atsushi; Inoue, Toru; Kanazawa, Akishige; Yamashita, Yoshito; Tsukamoto, Tadashi

    2015-05-01

    The administration of metronidazole is generally effective to treat amebic colitis. Fulminant amebic colitis is relatively rare, and it is associated with a high mortality rate. Three cases of fulminant amebic colitis were diagnosed in our hospital between 1993 and 2014. One of these patients died despite our efforts. Amebic colitis often presents with no obvious risk factors and with atypical clinical symptoms. Therefore, the diagnosis of amebic colitis can be difficult. Early diagnosis is the most important factor in successful treatment of fulminant amebic colitis. The present cases demonstrate that it is important to consider the possibility of amebic colitis during evaluation of the acute abdomen.

  5. [Infectious colitis. Endoscopy].

    PubMed

    Dive, C

    1986-11-01

    Colon and rectum localizations of an disease or a parasitosis depend essentially on the nature of the pathogenous agent and the host resistance. Acute enterocolitis is secondary to enterotoxinogenous germs (such as cholera vibrio), invasive germs (such as shigella), penetrating germs (such as salmonella); viruses are seldom concerned. Parasitic colitis include mostly amibiasis and bilharziosis. Infectious and parasitic enterocolitis may be transmitted sexually. On the other hand, certain venereal diseases have intestinal manifestations. Finally, in AIDS, timely gastro-intestinal infections develop. The diagnosis rests on endoscopy, histological examination and biological and parasitological samplings.

  6. Refractory Ulcerative Colitis Treatment

    PubMed Central

    Green, Jesse A.

    2007-01-01

    Treatment of refractory ulcerative colitis (UC) is a common clinical challenge. In either acute or chronic refractory UC, the disease may continue to remain active, even though the patient is on appropriate therapy. It is important to reassess and characterize the patient's disease before adding new medications to the current medical regimen. After determining the current extent and severity of the UC—ruling out other causes of bloody diarrhea and determining what complications are present—new treatment approaches can then be started. It is critical to first optimize oral 5-aminosalicylic acid (5-ASA) therapy combined with rectal 5-ASA or corticosteroid suppositories, plus corticosteroid or 5-ASA enemas or foam preparations. Oral or intravenous corticosteroids are appropriate to use if needed, but alternative approaches must be used for long-term maintenance. 6-Mercaptopurine (6-MP) or azathioprine can be very helpful for severe chronic refractory UC. In those patients who do not respond to 5-ASA medications, corticosteroids, and 6-MP or azathioprine, infliximab offers an important approach for induction and maintenance of remission for refractory chronic ulcerative colitis as well as for select cases of refractory acute UC. Cyclosporine use is an alternative medical approach for the refractory acute UC patient. Colectomy with ileal pouch-anal anastomosis remains a valuable option for the refractory chronic or acute UC patient, because it can provide both a “cure” for the disease, as well as eliminate ineffective medications with their associated side effects. PMID:21960779

  7. Medical therapy for ulcerative colitis.

    PubMed

    Hanauer, S B

    2000-07-01

    Last year was not a banner year for developments in medical therapy for ulcerative colitis. In contrast to the expansion of therapies for Crohn disease, treatment for ulcerative colitis was evolutionary, at best, leading many patients to seek alternative medical approaches. Nevertheless, there have been advances in the application of aminosalicylates and immune modifiers for ulcerative colitis. Additional, nonconventional approaches include nicotine, probiotics, dietary therapies, and heparins. Several novel approaches have arisen from animal models, including additional means of inhibiting nuclear factor-kappaB and targeting of tumor necrosis factor-alpha.

  8. Computed tomography of neutropenic colitis

    SciTech Connect

    Frick, M.P.; Maile, C.W.; Crass, J.R.; Goldberg, M.E.; Delaney, J.P.

    1984-10-01

    Four patients developed neutropenic colitis as a complication of acute leukemia (three) or aplastic anemia (one). On computed tomography (CT), neutropenic colitis was characterized by cecal wall thickening (four) and pneumatosis (one). Intramural areas of lower density presumably reflected edema or hemorrhage. Clinical improvement and return of adequate numbers of functioning neutrophils coincided with decrease in cecal wall thickening on CT. Prompt radiologic recognition of this serious condition is crucial, since surgical intervention is probably best avoided.

  9. [MICROSCOPIC COLITIS: THE CLINICAL CASE].

    PubMed

    Kulygina, Y A; Skalinskaya, M I; Ageeva, T A

    2015-01-01

    During past years incidence and prevalence of microscopic colitis (MC) have increased, that is possible caused to the improvement of knowledge of doctors about the disease. This article contain modern views on epidemiology, diagnostic and variant of microscopic colitis treatment. A typical clinical picture of MC in the form of recurrent a watery diarrhea, with the absence of pathologic changes at roentgenologic and endoscopic investigations is described with the example of a clinical case.

  10. Ciclosporin and refractory colitis.

    PubMed

    Hawthorne, A Barney

    2003-03-01

    Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.

  11. Clinical course of ulcerative colitis.

    PubMed

    Cottone, M; Scimeca, D; Mocciaro, F; Civitavecchia, G; Perricone, G; Orlando, A

    2008-07-01

    To provide a review of studies on prognosis in ulcerative colitis by reviewing the relevant population-based cohort studies. On the basis of incidence and population studies, ulcerative colitis has a favourable clinical course, with good quality of life, a chronic course characterized by at least one relapse, and a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe ulcerative colitis have a higher risk of colectomy, and some clinical variables may predict the disease's clinical course. Most patients respond to steroids and only a low percentage become dependent, or non-responders to steroids. Patients who have a long-lasting ulcerative colitis (>10 years) or are affected by an extensive disease have an increased risk of developing colorectal cancer, while those treated with immunosuppressants for long period of time may have an increased risk of developing lymphomas. Data on mortality in ulcerative colitis patients are not homogeneous, but if a real risk exists it is in patients with extensive or severe disease. The evidence that patients with severe ulcerative colitis are often non-smokers may explain why in one study the mortality rate was lower.

  12. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis

    PubMed Central

    Tschurtschenthaler, Markus; Kachroo, Priyadarshini; Heinsen, Femke-Anouska; Adolph, Timon Erik; Rühlemann, Malte Christoph; Klughammer, Johanna; Offner, Felix Albert; Ammerpohl, Ole; Krueger, Felix; Smallwood, Sébastien; Szymczak, Silke; Kaser, Arthur; Franke, Andre

    2016-01-01

    Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0DSS), or non-supplemented tap water (F0Ctrl) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0DSS males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0DSS mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0Ctrl males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  13. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

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

    PubMed

    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.

  15. "Cat scratch colon" in a patient with ischemic colitis.

    PubMed

    Park, Eui Ju; Lee, Joon Seong; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-03-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon.

  16. "Cat Scratch Colon" in a Patient with Ischemic Colitis

    PubMed Central

    Park, Eui Ju; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-01-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon. PMID:25844349

  17. Haemorrhagic Colitis Caused by Dasatinib

    PubMed Central

    Patodi, Nishant; Sagar, Nidhi; Rudzki, Zbigniew; Langman, Gerald; Sharma, Naveen

    2012-01-01

    Gastrointestinal bleeding appears to be a common adverse event associated with dasatinib therapy. Here we present a case of a 59-year-old man with chronic myeloid leukaemia (CML) developing the rarest complication of haemorrhagic colitis with dasatinib therapy which resolved rapidly after treatment withdrawal. PMID:23316400

  18. Behavioral Treatment of Mucous Colitis

    ERIC Educational Resources Information Center

    Youell, Katherine J.; McCullough, James P.

    1975-01-01

    A 22-year-old female graduate student who suffered colitis attacks at the onset of therapy was apparently successfully treated by a procedure in which the therapist labeled antecedent stress events that appeared to be precipitating the attacks. The client was then taught a behavioral coping strategy to counter the stress events. (Author)

  19. [Ulcerative colitis and cytomegalovirus infection].

    PubMed

    Tárraga Rodríguez, I; Ferreras Fernández, P; Vicente Gutiérrez, M; de Arriba, J J; García Mouriño, M L

    2003-02-01

    Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.

  20. Genetics Home Reference: ulcerative colitis

    MedlinePlus

    ... colitis is unknown because many genetic and environmental factors are likely to be involved. Even though the inheritance ... JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies ...

  1. Colitis in chronic granulomatous disease

    PubMed Central

    Schappi, M; Smith, V; Goldblatt, D; Lindley, K; Milla, P

    2001-01-01

    BACKGROUND—Involvement of the gut in chronic granulomatous disease (CGD) has been previously described and colitis highlighted. However, the nature and histopathology of the colitis are unclear and have been thought to be non-specific or similar to Crohn's disease.
METHODS—Seven patients with CGD, suffering from gastrointestinal symptoms were prospectively studied.
RESULTS—All patients had anaemia; other symptoms were failure to thrive (5/7) and diarrhoea (5/7). Most had microcytic anaemia (5/7), increased platelets (7/7), and increased erythrocyte sedimentation rate (6/6). Endoscopically there was a friable erythematous mucosa in 6/7. The histological features present in all patients consisted of a colitis with paucity of neutrophils, increased numbers of eosinophils, eosinophilic crypt abscesses, pigmented macrophages, and nuclear debris. In some granulomas were present (2/7).
CONCLUSIONS—Colitis is a common cause of gastrointestinal symptoms in CGD and is caused by a non-infective inflammatory process. The histology has specific features, which are distinctive from those seen in Crohn's disease.

 PMID:11159292

  2. Behavioral Treatment of Mucous Colitis

    ERIC Educational Resources Information Center

    Youell, Katherine J.; McCullough, James P.

    1975-01-01

    A 22-year-old female graduate student who suffered colitis attacks at the onset of therapy was apparently successfully treated by a procedure in which the therapist labeled antecedent stress events that appeared to be precipitating the attacks. The client was then taught a behavioral coping strategy to counter the stress events. (Author)

  3. Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group.

    PubMed

    Münch, A; Aust, D; Bohr, J; Bonderup, O; Fernández Bañares, F; Hjortswang, H; Madisch, A; Munck, L K; Ström, M; Tysk, C; Miehlke, S

    2012-10-01

    Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  4. Advances for improved diagnosis of microscopic colitis in patients with chronic diarrhoea.

    PubMed

    Zabana, Yamile; Ferrer, Carme; Aceituno, Montserrat; Salas, Antonio; Fernández-Bañares, Fernando

    2017-02-01

    Microscopic colitis is a generic term that includes 2 main forms, collagenous colitis and lymphocytic colitis, and describes a form of inflammatory bowel disease with a chronic and relapsing course. The incidence of microscopic colitis is between 2 and 8 times higher in women than in men, although age, more than sex, increases the risk of collagenous colitis (odds ratio [OR] 8.3 for age ≥65 vs. <65 and OR 2.8 for women). The main symptom is chronic non-bloody watery diarrhoea. Other common symptoms include abdominal pain (50%-70%), with the result that many patients with microscopic colitis meet criteria for irritable bowel syndrome. Colonoscopy with multiple colonic biopsies is currently recommended, as histological changes are the main characteristic feature. The colonic mucosa is macroscopically normal, although certain minimal endoscopic abnormalities have been described.

  5. β-lactam-associated eosinophilic colitis.

    PubMed

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-06-23

    A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of β-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with β-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids.

  6. Clear cell colitis: A form of microscopic colitis in children

    PubMed Central

    Józefczuk, Jan; Wozniewicz, Bogdan Marian

    2008-01-01

    AIM: To describe a new clinical and pathological subtype of microscopic colitis in children. METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described. RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple’s disease), and neuronal intestine dysplasia. Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages. CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis, sometimes coexisting with allergy. PMID:18186560

  7. [Colitis cystica profunda: report of one case].

    PubMed

    de Toro C, Gonzalo; Villaseca H, Miguel; Roa S, Juan Carlos

    2007-06-01

    Colitis cystica profunda is a benign condition that can be confused with adenocarcinoma. We report a 35 year-old woman that received radiotherapy for a uterine cervical carcinoma who presented intermittent hematochezia three times after ending the therapy. This episode was diagnosed and treated as a radiation colitis and the patient remained asymptomatic for six years. After this period she presented again intermittent hematochezia and a rectal mass that was surgically removed. The pathology report disclosed a colitis cystica profunda.

  8. Antibiotic-associated colitis and cystic fibrosis.

    PubMed

    Pokorny, C S; Bye, P T; MacLeod, C; Selby, W S

    1992-09-01

    The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed.

  9. [Treatment of severe ulcerative colitis flares].

    PubMed

    Aceituno, Montserrat; Montserrat, Aceituno; Zabana, Yamile; Yamile, Zabana; Esteve, Maria; Maria, Esteve

    2014-10-01

    The treatment of severe ulcerative colitis remains a challenge for gastroenterologists. A not inconsiderable number of patients will experience severe flares throughout their lives and will require hospitalization. Mortality in severe ulcerative colitis is still high and consequently treatment must be aggressive, avoiding delays in rescue therapies or even surgery. The aim of this review was to describe the medical treatment of severe ulcerative colitis, highlighting recent therapeutic advances.

  10. Polymyositis associated with ulcerative colitis.

    PubMed Central

    Chugh, S; Dilawari, J B; Sawhney, I M; Dang, N; Radotra, B D; Chawla, Y K

    1993-01-01

    An elderly woman with chronic ulcerative colitis who developed proximal muscle weakness, increased serum creatine phosphokinase activity, and histological and electromyographic abnormalities characteristic of polymyositis is described. Treatment with corticosteroids and 5-acetylsalicylic acid was followed by a remission in bowel symptoms, improvement in muscle power, and reversal of electromyographic changes. An autoimmune link between the two disorders seems likely. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8491410

  11. IMMUNOLOGICAL STUDIES IN ULCERATIVE COLITIS

    PubMed Central

    Lagercrantz, R.; Hammarström, S.; Perlmann, P.; Gustafsson, B. E.

    1968-01-01

    The incidence and height of antibody titers to colon, assayed by indirect hemagglutination with a heat stable colon extract from germ free rats, is significantly higher in sera from patients with ulcerative colitis than in those from healthy controls or from patients with amebic liver abscess or dysentery. While sera from ulcerative colitis patients and controls are indistinguishable in regard to incidence and height of antibody titers to Forsman antigen, Staphylococcus aureus S 209, Clostridium difficile, and several common strains of E. coli, they have elevated titers and increased incidence of antibodies to a heat stable antigen of E. coli O14. Patients with amebic dysentery have normal titers of such antibodies. Absorption of patients' sera with E. coli O14 antigen inhibits the colon directed hemagglutination reaction in approximately 30% of the cases tested. Likewise, the anti-E. coli O14 reaction can sometimes be inhibited with the colon extract. Other E. coli strains and other bacteria are inactive or have only weak inhibitory activity. Hemagglutination inhibition experiments show that germ free rat colon and E. coli O14 contain common structures, depicted by antibodies in the patients' sera. This pattern of reactivity closely resembles that seen in rats made autoimmune to colon by injection of newborn rabbit colon. E. coli O14 is known to carry a heterogenetic antigen present in lower concentration (or activity) in most Enterobacteriaceae. Hemagglutination inhibition experiments with rabbit antisera to E. coli O14 suggest that the antigen common for E. coli O14 and colon is related to this heterogenetic antigen. The findings imply that this antigen, which is constantly present in low concentrations in the human colon, may give rise to anticolon antibody formation in ulcerative colitis through breakage of tolerance. Since this antigen is present in healthy individuals as well, additional factors are required to explain the induction of anti

  12. Reaginic hypersensitivity in ulcerative colitis

    PubMed Central

    Jewell, D. P.; Truelove, S. C.

    1972-01-01

    Reaginic hypersensitivity in ulcerative colitis has been investigated in respect of a hypersensitivity to the cow's milk proteins and the frequency of atopic asthma, hay fever, and eczema. Intradermal tests were frequently positive, especially to casein, but the results did not differ from those found in healthy individuals and in groups of patients with Crohn's disease, hypolactasia, and the irritable colon syndrome. No circulating IgE-specific antibodies to the milk proteins were found. An increased frequency of atopic diseases was found in patients suffering from ulcerative colitis (15·7%) and Crohn's disease (13·3%) compared with the findings in a control group (1·2%). It is concluded that, if an allergy to milk proteins is a factor in the pathogenesis of ulcerative colitis, it is not mediated by reaginic antibodies. It is possible, however, that the frequent occurrence of atopy indicates a susceptibility to develop reaginic responses even though this mechanism does not apply to the milk proteins. PMID:4646293

  13. Diagnosis and management of microscopic colitis: current perspectives

    PubMed Central

    Bohr, Johan; Wickbom, Anna; Hegedus, Agnes; Nyhlin, Nils; Hultgren Hörnquist, Elisabeth; Tysk, Curt

    2014-01-01

    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 microscopic colitis. PMID:25170275

  14. Association of Serotonin Transporter Promoter Polymorphism (5-HTTLPR) with Microscopic Colitis and Ulcerative Colitis.

    PubMed

    Sikander, Arbab; Sinha, Saroj Kant; Prasad, Kaushal Kishor; Rana, Satya Vati

    2015-04-01

    Serotonin (5-HT) release and serotonin reuptake transporter (5-HTT) expression have been reported to be decreased in experimental colitis, in interleukin-10 knockout-associated colitis, and in patients with ulcerative colitis. Serotonin is known to play an important role in the pathogenesis of colitis, but individual genetic variants of 5-HTT gene in microscopic colitis and ulcerative colitis are not known. This study aimed to evaluate the association between the serotonin transporter gene promoter polymorphism (5-HTTLPR) and 5-HT concentration in microscopic colitis (MC) and ulcerative colitis (UC) patients. This prospective case-control study included 41 patients with microscopic colitis (age 19-82 years, mean 35 ± 13.6), 75 patients with ulcerative colitis (age 16-65 years, mean 38.5 ± 11.6), and 100 controls (age 20-64 years, mean 38 ± 11). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based assay. 5-HT levels were measured by ELISA. The frequency of the 5-HTTLPR (SS) genotype was significantly lower in MC (12 %) patients compared to controls (30 %) (p < 0.05). When the L/L and L/S genotypes were combined into one group, the frequencies of the non-S genotype were significantly higher than those of S/S genotype between the MC patients and the controls (p < 0.05). 5-HT levels were significantly higher in UC and MC patients compared to healthy controls (p < 0.01). A significant association was observed between LL genotype of 5-HTTLPR polymorphism and microscopic colitis, suggesting that 5-HTTLPR is a potential candidate gene involved in the pathogenesis of microscopic colitis. Serotonin levels were significantly higher in microscopic colitis and ulcerative colitis patients compared to healthy controls.

  15. Microscopic Colitis: Epidemiology, Pathophysiology, Diagnosis and Current Management—An Update 2013

    PubMed Central

    Storr, Martin Alexander

    2013-01-01

    Microscopic colitis is a common cause of chronic diarrhea. Over the last years the incidence and the prevalence of microscopic colitis are rising and this rise is largely attributed to a rising awareness, and concomitantly an increasing number of diagnoses are made. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic, intermittent, or chronic recurrent course. Following an unremarkable physical examination the diagnosis of microscopic colitis is made by colonoscopy, which shows essentially a normal colonic mucosa. Biopsies taken during the colonoscopy procedure will then finally establish the correct diagnosis. Histological workup can then confirm a diagnosis of microscopic colitis and can distinguish the two distinct histological forms, namely, collagenous colitis and lymphocytic colitis. Presently both forms are diagnosed and treated in the same way; thus the description of the two forms is not of clinical value, though this may change in future. Depending on the patients age and gender 10–30% of patients investigated for chronic diarrhea will be diagnosed with microscopic colitis if biopsies are taken. Microscopic colitis is most common in older patients, especially in female patients and is frequently associated with autoimmune disorders and the consumption of several drugs. This review summarizes the present knowledge of the epidemiology, the pathophysiology, and the diagnosis of microscopic colitis and discusses the former and the present treatment options. PMID:23691336

  16. Current and emerging biologics for ulcerative colitis.

    PubMed

    Park, Sung Chul; Jeen, Yoon Tae

    2015-01-01

    Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are be-ing investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are be-ing used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.

  17. Probiotics and prebiotics in ulcerative colitis.

    PubMed

    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.

  18. Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

    ClinicalTrials.gov

    2017-01-11

    Ulcerative Colitis; Digestive System Diseases; Colitis, Ulcerative; Colitis; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Colonic Diseases; Autoimmune Disease; Abdominal Pain

  19. Peculiar Presentation of Ulcerative Colitis

    PubMed Central

    Diab, Amany; Ahmed, Ayman; Abohamad, Samar; Elgendy, Hala

    2016-01-01

    Ulcerative colitis (UC) is a chronic inflammatory and recurrent disorder that is characterized by bowel inflammation. Among the extraintestinal manifestations (EIMs) that associate UC are the joints and renal manifestations. Joint affection in the form of arthritis can precede the intestinal manifestations of UC. However, renal affection with amyloidosis does not precede the UC diagnosis. Herein, we report a case of 26-year-old male diagnosed with UC after having peripheral arthritis for long time in addition to spondylitis and kidney amyloidosis. PMID:27042365

  20. Colitis after polytrauma: case report.

    PubMed

    Carter, William E; Darko, Isaac A; Chandan, Priya; Pai, Ajit B

    2014-01-01

    Across the medical literature, delayed diagnosis and treatment leads to more costly and worse outcomes. Rehabilitation patients, especially those with polytrauma, often have a complex mixture of medical, social, and psychological health problems that can impair effective diagnosis and treatment. The case presentation describes the procession toward the diagnosis of ulcerative colitis in a preinjury asymptomatic male, suggesting a potential mechanism for its emergence and describing the effect of delayed diagnosis on the efficiency of rehabilitative care. As such, the differential diagnosis for early posttraumatic diarrhea should remain broad, particularly if unexplained or ineffectively controlled.

  1. Takayasu arteritis and ulcerative colitis; coexistence or misdiagnosis?

    PubMed

    Azak, A; Huddam, B; Koçak, G; Kiliç, F; Koçak, E; Duranay, M

    2012-03-01

    Takayasu arteritis is a chronic inflammatory disease that primarily affects large arteries such as the aorta and its proximal branches. The association between Takayasu arteritis and ulcerative colitis is an extremely rare condition. Ulcerative colitis is an inflammatory bowel disease, clinical presentation is not specific and may mimic Crohn's disease, radiation colitis, ischemic colitis, a variety of infectious processes, and colitis related to medications. Herein we report a case of Takayasu arteritis who had been misdiagnosed and treated as ulcera-

  2. [Colitis ulcerosa and opioid addiction].

    PubMed

    Häuser, W; Lachiheb, H; Grandt, D

    2002-05-01

    The occurrence of an opioid addiction within an opioid treatment of pain or diarrhoea in inflammatory bowel disease is rarely reported. We report on a 36-year-old male with a 14 years lasting left sided chronic ulcerative colitis who developed after the initiation of a therapy with tincture of opium because of abdominal pain and diarrhoea an opioid addiction with the consumption of opium and later buprenorphin. Additionally to the diagnostics and therapy of the ulcerative colitis a detoxication was carried out. The diarrhoea slightly increased during the buprenorphin withdrawal. Diarrhoea refractory to other treatment should be treated by loperamid because of its lacking effects on the central nervous system. In chronic abdominal or musculoskeletal pain in inflammatory bowel disease opioids can be used if no surgical or other medical pain relief is possible. A consequent control of the therapeutic and side effects of the opioid therapy is necessary, especially of an abuse of opioid medication. The published case reports of a therapeutic induction of opioid addiction demonstrate that psychiatric comorbidity is an essential or even necessary risk factor. A checklist with seven criteria of opioid addiction during opioid therapy is presented.

  3. Rosiglitazone for Active Ulcerative Colitis

    PubMed Central

    Lewis, James D.; Lichtenstein, Gary R.; Deren, Julius J; Sands, Bruce E.; Hanauer, Stephen B.; Katz, Jeffry A.; Lashner, Bret; Present, Daniel H.; Chuai, Shaokun; Ellenberg, Jonas H.; Nessel, Lisa; Wu, Gary D.

    2008-01-01

    Background Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARγ), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis. Methods This multicenter randomized, double blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia™) 4 mg orally twice daily versus placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo Score. The primary endpoint was clinical response (≥ 2 point reduction) at week 12. Clinical remission (Mayo Score ≤2), endoscopic remission, and quality of life were secondary outcomes. Results After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (p=0.04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (p=0.01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs. 2% placebo, p=0.34). Clinical improvement was evident as early as 4 weeks (p=0.049). Quality of life was significantly improved at week 8 (p=0.01) but not at week 4 (p=0.48) or 12 (p=0.14). Serious adverse events were rare. Conclusions Rosiglitazone was efficacious in the treatment of mild to moderately active ulcerative colitis. PMID:18325386

  4. Crohn's Disease and Ulcerative Colitis: Emotional Factors

    MedlinePlus

    ... correct this common and erroneous impression. ARE CERTAIN PERSONALITY TYPES MORE PRONE TO DEVELOP ULCERATIVE COLITIS OR ... of medical disorders that were characteristic of certain personality traits and a specific biological predisposition. The latest ...

  5. Scientists Spot Genes Behind Crohn's, Ulcerative Colitis

    MedlinePlus

    ... medlineplus.gov/news/fullstory_166957.html Scientists Spot Genes Behind Crohn's, Ulcerative Colitis Large study finds key ... Researchers say they've come closer to pinpointing genes linked with inflammatory bowel diseases such as Crohn's ...

  6. Crohn's Disease and Ulcerative Colitis: Emotional Factors

    MedlinePlus

    ... correct this common and erroneous impression. ARE CERTAIN PERSONALITY TYPES MORE PRONE TO DEVELOP ULCERATIVE COLITIS OR ... of medical disorders that were characteristic of certain personality traits and a specific biological predisposition. The latest ...

  7. The economics of adalimumab for ulcerative colitis.

    PubMed

    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.

  8. Intestinal microbiota and ulcerative colitis.

    PubMed

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Murine models of ulcerative colitis.

    PubMed

    Flynn, Christopher; Levine, Joel; Rosenberg, Daniel W

    2003-06-01

    Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology limited to the large intestine. The disease is prevalent in industrial societies and is associated with specific ethnic populations. A number of murine models, each focused on distinct aspects of the disease process, were developed over the past 20 years to further our understanding of the pathogenesis of UC. These models have been and remain our best resource for the study of the disorder as a result of their homology to human UC and the ease in which they can be manipulated and examined. This review examines and distills what has been leamed from these models and how this information is related back to human UC.

  10. Radiographical evaluation of ulcerative colitis

    PubMed Central

    Deepak, Parakkal; Bruining, David H.

    2014-01-01

    Radiographical modalities have become important diagnostic tools in cases of ulcerative colitis (UC). Imaging can be used non-invasively to determine the extent of involvement, severity of disease and to detect disease-related complications and extra-intestinal inflammatory bowel disease (IBD) manifestations. While abdominal X-rays and barium enemas still retain their relevance in specific clinical settings, the use of computed tomography enterography (CTE) or magnetic resonance enterography (MRE) are now used as first-line investigations to exclude active small bowel disease in IBD patients and can be utilized to detect active colonic inflammation. Additionally, CT colonography and MR colonography are emerging techniques with potential applications in UC. Ultrasonography, leukocyte scintigraphy and positron emission tomography are novel abdominal imaging modalities currently being explored for IBD interrogations. This plethora of radiological imaging options has become a vital component of UC assessments. PMID:24843072

  11. Biological therapy for ulcerative colitis

    PubMed Central

    Arora, Zubin; Shen, Bo

    2015-01-01

    Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) worldwide. Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade. A number of biological agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of UC and several more are currently in various phases of drug development. The commonly used agents include TNFα antagonists (e.g. infliximab, adalimumab, and golimumab) and anti-integrin agents (vedolizumab). These biological agents have profoundly influenced the management of UC patients, especially those with refractory disease. This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC. PMID:25344680

  12. [Caesarean section for ulcerative colitis].

    PubMed

    Unda-Franco, Eduardo; Ramírez-Avilés, Eva María; Moreno-de Gante, Leonardo; González, Quintín Héctor

    2011-02-01

    We present a case of a 35-year-old patient with diagnosis of ulcerative colitis that presented failure and complications associated with medical treatment; with a report of a colonoscopy and biopsy of pancolitis with severe activity. The patient was submitted to laparoscopic restorative total proctocolectomy with ileal "J" pouch anal anastomosis. Two months later the ileostomy was reversed. The patient received progesterone at the same time she was receiving immunosuppressive drugs. This was suspended two months after the second colon surgery. The patient did not require treatment with ovulation induction to achieve pregnancy. At the fourth month of gestation, the patient developed a perianal abscess, which was successfully drained. After multidisciplinary assessment in week 38 of gestation, it was decided to perform cesarean birth as a way to not affect the ileal pouch and the anastomosis of the digestive tract. At present time, the patient has had no further complications.

  13. Microscopic colitis: clinical and pathologic perspectives.

    PubMed

    Münch, Andreas; Langner, Cord

    2015-02-01

    Microscopic colitis is a chronic inflammatory bowel disease characterized by chronic nonbloody diarrhea and specific histopathology features. Active disease, defined as 3 or more stools or 1 or more watery stools per day, significantly reduces quality of life. Epidemiologic studies have found the incidence and prevalence of microscopic colitis to be comparable with those of Crohn's disease and ulcerative colitis. Nevertheless, microscopic colitis is still under-recognized in clinical practice-most health care workers know little about its etiology and pathophysiology. Furthermore, there are many challenges to the diagnosis and treatment of patients. We review the epidemiologic and clinical features of this disorder and discuss its pathogenesis. We also outline the criteria for histopathologic evaluation of microscopic colitis, recently published by the European Consensus on Inflammatory Bowel Disease, and discuss a treatment algorithm created by the European Microscopic Colitis Group. Treatment options for patients with budesonide-refractory disease are discussed. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Colonic mucus, smoking and ulcerative colitis.

    PubMed

    Pullan, R D

    1996-03-01

    Human colonic mucosal protection is not fully understood but may in part rely on a layer of mucus gel adherent to the mucosa. Ulcerative colitis may occur if mucosal protection breaks down. Two studies are presented, both of which relate to the aetiology of ulcerative colitis. First, a layer of adherent mucus gel was demonstrated by a simple, reliable method. Measurements of mucus layer thickness were made in freshly resected colonic specimens and shown to increase from a mean of 107 microns on the right colon to 155 microns in the rectum. In ulcerative colitis the layer is significantly thinner or absent, whereas in Crohn's disease the colonic mucus layer is significantly thicker. Second, the relationship between smoking and colitis is explored by a double-blind, randomised and placebo-controlled trial of transdermal nicotine in active disease. Significant clinical benefit was seen, indicating nicotine may be both useful therapeutically and the component of tobacco smoke that acts to protect against colitis. Since smoking and nicotine have actions on mucosae and mucus in other organs, it is argued that there is a mucus deficiency in ulcerative colitis that smoking acts to reverse.

  15. Systematic review with meta-analysis: diagnostic overlap of microscopic colitis and functional bowel disorders.

    PubMed

    Guagnozzi, D; Arias, Á; Lucendo, A J

    2016-04-01

    Microscopic colitis shares certain common clinical manifestations with functional bowel disorders, especially diarrhoea-dominant irritable bowel syndrome (IBS) and functional diarrhoea. However, the exact relationship between microscopic colitis and functional bowel disorders has not been systematically assessed. To conduct a systematic review and meta-analysis on the diagnostic overlap between functional bowel disorders and microscopic colitis. We searched MEDLINE, EMBASE and SCOPUS databases, as well as the abstract books of the major gastroenterology meetings, to investigate the prevalence of microscopic colitis among patients with functional bowel disorders (considering all subtypes of both disorders) and vice versa. Data were pooled with a random-effects model. Of 227 references identified, data were collected from 26 studies and a total of 5,099 adult patients. The pooled prevalence any type of functional bowel disorders in patients who present diagnostic criteria of microscopic colitis was 39.1% (95% CI: 22.8-56.6%; I(2) : 97%) and was higher for lymphocytic colitis than for collagenous colitis (40.7% vs. 28.4%, respectively; P = 0.58). The prevalence of microscopic colitis in functional bowel disorders patients was 7% (95% CI: 3.6-11.4%), reaching 9.8% (95% CI: 4.4-17.1%; I(2) : 95%) in patients exhibiting diarrhoea-dominant IBS, nonsignificantly higher than microscopic colitis rates among patients with constipation-dominant IBS (1.3%) or mixed-dominant IBS (1.9%). There is a significant overlap of symptoms between microscopic colitis and functional bowel disorders, especially in diarrhoeal subtypes. The high proportion of microscopic colitis among diarrhoea-dominant functional syndromes should serve as a call for more active diagnosis in selected patients. © 2016 John Wiley & Sons Ltd.

  16. Melatonin improves experimental colitis with sleep deprivation

    PubMed Central

    PARK, YOUNG-SOOK; CHUNG, SOOK-HEE; LEE, SEONG-KYU; KIM, JA-HYUN; KIM, JUN-BONG; KIM, TAE-KYUN; KIM, DONG-SHIN; BAIK, HAING-WOON

    2015-01-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n=24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was

  17. Melatonin improves experimental colitis with sleep deprivation.

    PubMed

    Park, Young-Sook; Chung, Sook-Hee; Lee, Seong-Kyu; Kim, Ja-Hyun; Kim, Jun-Bong; Kim, Tae-Kyun; Kim, Dong-Shin; Baik, Haing-Woon

    2015-04-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n = 24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was

  18. Nicotine suppresses acute colitis and colonic tumorigenesis associated with chronic colitis in mice.

    PubMed

    Hayashi, Shusaku; Hamada, Takayuki; Zaidi, Syed Faisal; Oshiro, Momoe; Lee, Jaemin; Yamamoto, Takeshi; Ishii, Yoko; Sasahara, Masakiyo; Kadowaki, Makoto

    2014-11-15

    Ulcerative colitis is a chronic inflammatory disease that frequently progresses to colon cancer. The tumor-promoting effect of inflammation is now widely recognized and understood. Recent studies have revealed that treatment with nicotine ameliorates colitis in humans and experimental murine models, whereas the effect of nicotine on colitis-associated colonic tumorigenesis remains unclear. In the present study, we examined the effect of nicotine on the development of acute colitis and colitis-associated cancer (CAC). The acute colitis model was induced by treatment with 3% dextran sulfate sodium (DSS) for 7 days, whereas the CAC model was induced by a combination of azoxymethane and repeated DSS treatment. Nicotine and a selective agonist of the α7-nicotinic acetylcholine receptor (α7-nAChR) reduced the severity of DSS-induced acute colonic inflammation. In addition, the suppressive effect of nicotine on acute colitis was attenuated by an antagonist of α7-nAChR. Furthermore, nicotine inhibited the IL-6 production of CD4 T cells in the DSS-induced inflamed colonic mucosa. We found that nicotine significantly reduced the number and size of colonic tumors in mice with CAC. Nicotine markedly inhibited the elevation of TNF-α and IL-6 mRNA as well as phosphorylated signal transducer and activator of transcription (Stat) 3 expression in the colons of the tumor model mice. These results demonstrate that nicotine suppresses acute colitis and colitis-associated tumorigenesis, and this effect may be associated with the activation of α7-nAChR. Furthermore, it is presumed that nicotine downregulates the expression of inflammatory mediators such as IL-6/Stat3 and TNF-α, thereby reducing the colonic tumorigenesis associated with chronic colitis.

  19. The epidemiology of microscopic colitis in Olmsted County from 2002 to 2010: a population-based study.

    PubMed

    Gentile, Nicole M; Khanna, Sahil; Loftus, Edward V; Smyrk, Thomas C; Tremaine, William J; Harmsen, W Scott; Zinsmeister, Alan R; Kammer, Patricia P; Pardi, Darrell S

    2014-05-01

    The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study. Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota, who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010, based on biopsy results and the presence of diarrhea (N = 182; mean age at diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period. The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per 100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000 person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The incidence of microscopic colitis and its subtypes remained stable over the study period (P = .63). Increasing age (P < .001) and female sex (P < .001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis). The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Cytomegalovirus: associated ischemic colitis in an immunocompetent patient.

    PubMed

    Puerta, Ana; Priego, Pablo; Galindo, Julio

    2017-09-01

    Cytomegalovirus (CMV) colitis is a common entity in immunocompromised patients, being rare among immunocompetent individuals. In addition, its association with ischemic colitis is unusual in both groups of population. Rectal bleeding might occur in both entities and, occasionally, urgent surgical treatment may be required, associating high morbility rates. We report one case of cytomegalovirus colitis associated with severe ischemic colitis in a non- immunocompromised patient with favourable response to conservative management with antiviral therapy.

  1. Microscopic colitis: A review of etiology, treatment and refractory disease.

    PubMed

    Park, Tina; Cave, David; Marshall, Christopher

    2015-08-07

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis.

  2. Differential Angiogenic Regulation of Experimental Colitis

    PubMed Central

    Chidlow, John H.; Langston, Will; Greer, James J.M.; Ostanin, Dmitry; Abdelbaqi, Maisoun; Houghton, Jeffery; Senthilkumar, Annamalai; Shukla, Deepti; Mazar, Andrew P.; Grisham, Matthew B.; Kevil, Christopher G.

    2006-01-01

    Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract with unknown multifactorial etiology that, among other things, result in alteration and dysfunction of the intestinal microvasculature. Clinical observations of increased colon microvascular density during IBD have been made. However, there have been no reports investigating the physiological or pathological importance of angiogenic stimulation during the development of intestinal inflammation. Here we report that the dextran sodium sulfate and CD4+CD45RBhigh T-cell transfer models of colitis stimulate angiogenesis that results in increased blood vessel density concomitant with increased histopathology, suggesting that the neovasculature contributes to tissue damage during colitis. We also show that leukocyte infiltration is an obligatory requirement for the stimulation of angiogenesis. The angiogenic response during experimental colitis was differentially regulated in that the production of various angiogenic mediators was diverse between the two models with only a small group of molecules being similarly controlled. Importantly, treatment with the anti-angiogenic agent thalidomide or ATN-161 significantly reduced angiogenic activity and associated tissue histopathology during experimental colitis. Our findings identify a direct pathological link between angiogenesis and the development of experimental colitis, representing a novel therapeutic target for IBD. PMID:17148665

  3. EP4 Receptor–Associated Protein in Macrophages Ameliorates Colitis and Colitis-Associated Tumorigenesis

    PubMed Central

    Nakatsuji, Masato; Yasui, Mika; Komekado, Hideyuki; Higuchi, Sei; Fujikawa, Risako; Nakanishi, Yuki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Kita, Toru; Libby, Peter; Ikeuchi, Hiroki; Yokode, Masayuki; Chiba, Tsutomu

    2015-01-01

    Prostaglandin E2 plays important roles in the maintenance of colonic homeostasis. The recently identified prostaglandin E receptor (EP) 4–associated protein (EPRAP) is essential for an anti-inflammatory function of EP4 signaling in macrophages in vitro. To investigate the in vivo roles of EPRAP, we examined the effects of EPRAP on colitis and colitis-associated tumorigenesis. In mice, EPRAP deficiency exacerbated colitis induced by dextran sodium sulfate (DSS) treatment. Wild-type (WT) or EPRAP-deficient recipients transplanted with EPRAP-deficient bone marrow developed more severe DSS-induced colitis than WT or EPRAP-deficient recipients of WT bone marrow. In the context of colitis-associated tumorigenesis, both systemic EPRAP null mutation and EPRAP-deficiency in the bone marrow enhanced intestinal polyp formation induced by azoxymethane (AOM)/DSS treatment. Administration of an EP4-selective agonist, ONO-AE1-329, ameliorated DSS-induced colitis in WT, but not in EPRAP-deficient mice. EPRAP deficiency increased the levels of the phosphorylated forms of p105, MEK, and ERK, resulting in activation of stromal macrophages in DSS-induced colitis. Macrophages of DSS-treated EPRAP-deficient mice exhibited a marked increase in the expression of pro-inflammatory genes, relative to WT mice. By contrast, forced expression of EPRAP in macrophages ameliorated DSS-induced colitis and AOM/DSS-induced intestinal polyp formation. These data suggest that EPRAP in macrophages functions crucially in suppressing colonic inflammation. Consistently, EPRAP-positive macrophages were also accumulated in the colonic stroma of ulcerative colitis patients. Thus, EPRAP may be a potential therapeutic target for inflammatory bowel disease and associated intestinal tumorigenesis. PMID:26439841

  4. Segmental colitis associated diverticulosis syndrome

    PubMed Central

    Freeman, Hugh J

    2016-01-01

    Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn’s disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., “rectal sparing”) is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required. PMID:27688648

  5. Colonic mucosal pseudolipomatosis: disinfectant colitis?

    PubMed

    Kim, Su Jin; Baek, Il Hyun

    2012-01-01

    Colonic pseudolipomatosis is rare and its pathogenesis is still unclear. A number of mechanisms, including mechanical injury during an endoscopic procedure or chemical injury by disinfectant, seem to contribute to its pathogenesis. In our endoscopy unit, pseudolipomatosis occurred in an epidemic pattern after changing the endoscopic disinfectant from 2% glutaraldehyde to peracetic acid compound to decrease the length of endoscope reprocessing time. We assumed that pseudolipomatosis could be a type of chemical colitis produced by the residual disinfectant solution that remained on the surface or in a channel of the endoscope after reprocessing. The aim of this report was to highlight a series of 12 cases of colonic pseudolipomatosis in order to describe the endoscopic and pathological features and discuss the harmful effect of disinfectants as a possible cause of pseudolipomatosis. To identify the cause of the lesions, we systematically reviewed each patient history and the endoscopic and histological features. From March 2004 to February 2005, 1276 colonoscopies were performed and 12 cases (0.94%) of colonic pseudolipomatosis were diagnosed at the Kangnam Sacred Heart Hospital of Hallym University. The pathogenesis of colonic pseudolipomatosis is not well-known, but our experience indicates the endoscopic disinfectant as the probable cause of pseudolipomatosis rather than either mechanical traumatic injury or intraluminal air pressure-related injury.

  6. A rare case of infectious colitis.

    PubMed

    Kalakonda, Aditya; Garg, Shashank; Tandon, Suraj; Vinayak, Rakesh; Dutta, Sudhir

    2016-11-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for numerous infectious processes. Gastrointestinal tract involvement is rather rare and only a handful of cases of MRSA colitis have been reported in North America. We present a case of MRSA colitis in an adult without apparent risk factors. Abdominal computed tomography (CT) showed thickening of the sigmoid colon, indicative of colitis, and empiric therapy with ciprofloxacin and metronidazole was started. Initial work-up for infection-including blood and stool cultures, and stool Clostridium difficile toxin assay-was negative. The patient's clinical status improved but his diarrhea did not abate. Repetition of stool culture demonstrated luxuriant growth of MRSA sensitive to vancomycin. Oral vancomycin was administered and the patient's symptoms promptly ceased.

  7. Ulcerative colitis: a challenge to surgeons.

    PubMed

    Parray, Fazl Q; Wani, Mohd L; Malik, Ajaz A; Wani, Shadab N; Bijli, Akram H; Irshad, Ifat; Nayeem-Ul-Hassan

    2012-11-01

    Ulcerative colitis is a chronic disease that specifically affects the mucosa of the rectum and colon. Although the etiology of this recurring inflammatory disorder remains essentially unknown, there have been significant advances in identifying the likely genetic and environmental factors that contribute to its pathogenesis. The clinical course of the disease typically manifests with remissions and exacerbations characterized by rectal bleeding and diarrhea. Since ulcerative colitis most commonly affects patients in their youth or early middle age, the disease can have serious long-term local and systemic consequences. There is no specific medical therapy that is curative. Although medical therapy can ameliorate the inflammatory process and control most symptomatic flares, it provides no definitive treatment for the disease. Proctocolectomy or total removal of the colon and rectum provides the only complete cure; however, innovative surgical alternatives have eliminated the need for a permanent ileostomy. The aim of this review is to provide a detailed account of the surgical management of ulcerative colitis.

  8. Advances in endoscopic imaging in ulcerative colitis.

    PubMed

    Tontini, Gian Eugenio; Pastorelli, Luca; Ishaq, Sauid; Neumann, Helmut

    2015-01-01

    Modern strategies for the treatment of ulcerative colitis require more accurate tools for gastrointestinal imaging to better assess mucosal disease activity and long-term prognostic clinical outcomes. Recent advances in gastrointestinal luminal endoscopy are radically changing the role of endoscopy in every-day clinical practice and research trials. Advanced endoscopic imaging techniques including high-definition endoscopes, optical magnification endoscopy, and various chromoendoscopy techniques have remarkably improved endoscopic assessment of ulcerative colitis. More recently, optical biopsy techniques with either endocytoscopy or confocal laser endomicroscopy have shown great potential in predicting several histological changes in real time during ongoing endoscopy. Here, we review current applications of advanced endoscopic imaging techniques in ulcerative colitis and present the most promising upcoming headways in this field.

  9. Colitis: an unusual presentation of Wegener's granulomatosis

    PubMed Central

    Sinnott, Joseph Dalby; Matthews, Paul; Fletcher, Simon

    2013-01-01

    Wegener's granulomatosis (WG) also known as granulomatosis with polyangiitis (GPA) is an anti-neutrophil cytoplasmic antibody-positive (ANCA) vasculitis which most commonly affects the upper respiratory tract, lungs and kidneys. It is uncommon for colitis to be the primary reason for the first hospital admission related to WG. This case represents one of the few in the literature where colitis is associated with WG and in particular, where colonic involvement was the presenting symptom. The patient presented to hospital with a 3-day history of bloody diarrhoea and was treated for colitis. The disease progressed and during the second admission renal and pulmonary involvement was found. A renal biopsy showed a crescentic change and a CT-confirmed inflammatory changes in the caecum and ascending colon. A diagnosis of WG was made and appropriate treatment initiated. The patient is now in remission. PMID:23436885

  10. Fulminant amebic colitis in a homosexual man.

    PubMed

    Saltzberg, D M; Hall-Craggs, M

    1986-03-01

    This report describes a case of fulminant amebic colitis leading to perforation and death in a 35-yr-old homosexual man. Although Entamoeba histolytica may be isolated from stool specimens in 20 to 30% of selected homosexual populations, reports of severe or invasive disease are rare. Some workers have suggested that amebae are only passive colonizers of the colon in homosexual men. In our patient, pathological examination confirmed the presence of extensive colitis with penetration of amebae through the bowel wall. Pertinent data concerning pathogenicity of E. histolytica in homosexuals are reviewed and the public health implications of a virulent strain of amebae are discussed.

  11. Intensive intravenous regime for acute severe colitis.

    PubMed

    Banerjee, Rupa; Philip, Matthew; Bhatia, Shobna

    2014-08-01

    Acute severe exacerbation of ulcerative colitis is a potentially life threatening medical emergency. The management of acute severe ulcerative colitis depends on early recognition and prompt initiation of intensive intravenous treatment along with continuous objective monitoring for possible medical failure. The intensive regime is the accepted standard of care. This includes primarily a) intravenous corticosteroids, b) intravenous supportive management, and d) intravenous antibiotics in instances. This review discusses the timing, duration and dosage of the intensive intravenous treatment including the evidence based protocol for effective monitoring to enable timely escalation to second line therapy & colectomy.

  12. Evolving medical therapies for ulcerative colitis.

    PubMed

    Cohen, Russell D

    2002-12-01

    Therapies for patients with ulcerative colitis have, until recently, been limited in scope and efficacy. New formulations of mesalamine and corticosteroids have challenged the older therapies with respect to both efficacy and safety. The application of 6-mercaptopurine and azathioprine for steroid-refractory disease and maintenance of remission has resulted in studies of other candidate immunomodulatory agents. Biologic therapies targeting tumor necrosis factor, adhesion molecules, or other cytokines are under intense scrutiny as potential disease-altering agents that may even replace currently available products. Other approaches, including such wide-ranging products as heparin, nicotine, and probiotics, suggest that control of ulcerative colitis may require an individualized approach for each patient.

  13. CT findings in ulcerative, granulomatous, and indeterminate colitis.

    PubMed

    Gore, R M; Marn, C S; Kirby, D F; Vogelzang, R L; Neiman, H L

    1984-08-01

    Eight patients with ulcerative colitis, three with colitis indeterminate, and 15 patients with Crohn disease were studied by computed tomography (CT) to establish CT criteria for each disorder in hopes of providing a new diagnostic perspective useful in the radiographic evaluation of inflammatory colitis. The CT findings in ulcerative colitis included thickening of the colon wall (mean, 7.8 mm), which was characterized by inhomogeneous attenuation and a "target" appearance of the rectum, and proliferation of perirectal fat. Bowel wall thickening (mean, 13 mm) with homogeneous attenuation, fistula and abscess formation, and mesenteric abnormalities were observed in patients with Crohn colitis. Patients with colitis indeterminate showed colonic changes on CT observed in both disorders. Initial experience suggests that CT can differentiate patients with well established ulcerative and Crohn colitis.

  14. [Surgical options in ulcerative colitis].

    PubMed

    Hultén, L; Ecker, K W

    1998-01-01

    Surgery is needed in every second patient with pancolitis. Historically four surgical options have been developed: conventional ileostomy, ileorectostomy, continent ileostomy (Kock's pouch) and ileo-anal pouch. However, in emergent or unclear situations subtotal colectomy, ileostomy and preservation of the rectum is the most suitable operation. After recovery and in elective indications proctectomy and proctocolectomy establish the general surgical standard. Today, in most cases ileo-pouch-anal anastomosis is performed instead of creation of an ileostomy. Both lowered frequency of defecation and acceptable continence contribute to a better quality of life. However, functional disturbances are not uncommon and result in most cases from complications of the demanding technique. Definitive cure of the colitis is in interference with the risk of pouchitis in about 30%. The cumulative probability to loose the pouch may rise to 15-20% in the long-term course. Thus, ileorectostomy may be considered as a first step of surgical treatment, since pelvic nerve damage is excluded, function is much better and persistent proctitis can be treated topically. The attractively is that ileo-anal pouch can be performed later on, when decreasing function and increasing risk of malignant change will eventually require proctectomy. A Kock-pouch is seldom considered, especially in patients with ileostomy wishing sure fecal control. But the continent reservoir becomes more and more interesting again since it can be reconstructed from a failed ileo-anal pouch without loss of bowel. Conventional ileostomy should be reserved for patients not suitable for reconstructive methods or those who consider pough operations risk. However, it is the safest procedure with absolute cure of disease. The optimal choice of method considers medical and surgical aspects as well as patients conception and desire.

  15. Multidrug resistance gene and its relationship to ulcerative colitis and immune status of ulcerative colitis.

    PubMed

    Zhang, Y J; Xu, J J; Wang, P; Wang, J L

    2014-12-19

    We examined the relationship among the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp), ulcerative colitis, and immune status under ulcerative colitis. MDR1 P-gp expression and interleukin-8 levels in ulcerative colitis were determined using immunohistochemistry and a double-antibody sandwich avidin-biotin complex-enzyme-linked immunosorbent assay, respectively. Nitric oxide content and nitric oxide synthase activity in the colonic mucosa were determined using a colorimetric method; CD4(+) and CD25(+) T cell subset percentages in the peripheral blood were determined by flow cytometry. The positive expression rate of P-gp in patients with ulcerative colitis (17.4%) was significantly lower than that in the control group (31.4%). The expression rate decreased to 10.1, 9.2, and 8.3% after 12, 18, and 24 months of treatment, respectively, which were significantly lower than the expression rate before treatment (17.4%). P-gp expression levels during the remission phase and active phase of ulcerative colitis were 15.2 and 17.1%, respectively, which were significantly lower than that in normal controls (31.4%). Compared with P-gp-negative patients, nitric oxide content, nitric oxide synthase activity, and interleukin-8 levels were significantly higher in P-gp-positive patients with moderately active, severely active, early onset, chronic relapsing, chronic persistent, and acute fulminant ulcerative colitis. CD4(+) and CD25(+) T cell subsets were significantly lower in the peripheral blood of patients with severely active and acute fulminant ulcerative colitis than in control subjects. Expression of the multidrug resistance gene and its product P-gp was observed in normal colon tissues and may be closely related to ulcerative colitis.

  16. Cerebral Arterial Thrombosis in Ulcerative Colitis

    PubMed Central

    Casella, Giovanni; Cortelezzi, Claudio Camillo; Marialuisa, DeLodovici; Cariddi Lucia, Princiotta; Elena Pinuccia, Verrengia; Baldini, Vittorio; Segato, Sergio

    2013-01-01

    Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD). We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature. PMID:23864966

  17. Cerebral arterial thrombosis in ulcerative colitis.

    PubMed

    Casella, Giovanni; Cortelezzi, Claudio Camillo; Marialuisa, Delodovici; Cariddi Lucia, Princiotta; Elena Pinuccia, Verrengia; Baldini, Vittorio; Segato, Sergio

    2013-01-01

    Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD). We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature.

  18. Approach to the patient with infectious colitis.

    PubMed

    DuPont, Herbert L

    2012-01-01

    To provide current recommendations for evaluation and treatment of patients with infectious colitis. Infectious colitis is diagnosed in someone with diarrhea and one or more of the following: fever and/or dysentery, stools containing inflammatory markers such as leukocytes, lactoferrin, or calprotectin, or positive stool culture for an invasive or inflammatory bacterial enteropathogen including Shigella, Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (STEC) or Clostridium difficile, or colonic inflammation by endoscopy. Standard stool culture should be performed in patients with infectious colitis. Epidemiologic findings including prior international travel, shellfish-associated diarrhea, living in parasite-endemic regions may suggest the need for specialized studies of etiology. When STEC is suspected as a pathogen because only low grade or no fever is seen in a patient with acute dysentery, a competent laboratory should look for E. coli O157:H7 and Shiga toxin directly in stool. Once laboratory diagnosis is made, pathogen-specific antimicrobial therapy should be initiated for all forms of infectious colitis other than STEC. For empiric treatment of febrile dysenteric diarrhea invasive bacterial enteropathogens (Shigella, Salmonella, and Campylobacter) should be suspected and adults may be treated empirically with 1000mg azithromycin in a single dose.

  19. Does lymphocytic colitis always present with normal endoscopic findings?

    PubMed

    Park, Hye Sun; Han, Dong Soo; Ro, Young Ouk; Eun, Chang Soo; Yoo, Kyo Sang

    2015-03-01

    Although normal endoscopic findings are, as a rule, part of the diagnosis of microscopic colitis, sev-eral cases of macroscopic lesions (MLs) have been reported in collagenous colitis, but hardly in lymphocytic colitis (LC). The aim of this study was to investigate the endoscopic, clini-cal, and histopathologic features of LC with MLs. A total of 14 patients with LC who were diagnosed between 2005 and 2010 were enrolled in the study. Endoscopic, clini-cal, and histopathologic findings were compared retrospec-tively according to the presence or absence of MLs. MLs were observed in seven of the 14 LC cases. Six of the MLs exhibited hypervascularity, three exhibited exudative bleeding and one exhibited edema. The patients with MLs had more severe diarrhea and were taking aspirin or pro-ton pump inhibitors. More intraepithelial lymphocytes were observed during histologic examination in the patients with MLs compared to the patients without MLs, although this difference was not significant. The numbers of mononuclear cells and neutrophils in the lamina propria were independent of the presence or absence of MLs. LC does not always present with normal endoscopic findings. Hyper-vascularity and exudative bleeding are frequent endoscopic findings in patients with MLs. (Gut Liver, 2015;9197-201).

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

    PubMed Central

    Pisani, Laura Francesca; Tontini, Gian Eugenio; Marinoni, Beatrice; Villanacci, Vincenzo; Bruni, Barbara; Vecchi, Maurizio; Pastorelli, Luca

    2017-01-01

    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. PMID:28540290

  1. The Temporal Evolution of Histological Abnormalities in Microscopic Colitis.

    PubMed

    Rasmussen, Julie; Engel, Peter Johan Heiberg; Wildt, Signe; Fiehn, Anne-Marie Kanstrup; Munck, Lars Kristian

    2016-03-01

    Microscopic colitis (MC) is a common cause of chronic watery diarrhoea but long-term follow-up data are sparse. We performed a retrospective review of health records and all pathology reports in a regional cohort of patients with MC to describe the change in pre- and post-diagnostic colon biopsies. MC was diagnosed in 468 patients with collagenous colitis (CC), 361 with lymphocytic colitis (LC) and 226 with incomplete MC (MCi). The 2014 incidence of CC, LC and MCi was 14.5, 14.9 and 5 per 10(5). Biopsies from both right and left colon were obtained in 237 (51%) patients with CC, 200 (55%) with LC and 107 (47%) with MCi. The diagnostic sensitivities of both left- and right-sided biopsies for MC were high and did not differ. Pre-diagnostic biopsies were obtained in 150 patients and lamina propria inflammation was described in 59, 47 and 43% of patients with a diagnosis of CC, LC and MCi respectively within 1 year, while histology was normal in 16, 13 and 21%. Post-diagnostic biopsies were obtained in 283 patients. MC persisted for up to one year in 77% with CC, 64% with LC and 45% with MCi, of whom 6, 9 and 18% respectively changed to a different MC subgroup. Colonic biopsies obtained prior to the MC diagnosis often revealed increased lamina propria inflammation. The pathological changes of CC and LC are more persistent than those of MCi. Biopsies from the descending or sigmoid colon are sufficient to elucidate whether a patient with chronic watery diarrhoea has MC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice

    PubMed Central

    Chassaing, Benoit; Aitken, Jesse D.; Malleshappa, Madhu; Vijay-Kumar, Matam

    2014-01-01

    Inflammatory bowel diseases (IBD) mainly comprised of Ulcerative Colitis and Crohn's Disease are complex and multifactorial disease with unknown etiology. For the past 20 years, to study human IBD mechanistically, number of murine models of colitis has been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate number potential therapeutics. Among various chemical induced colitis models, DSS-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that need to be considered when employed. The current protocol aimed to extensively describe the DSS-induced colitis model, focusing on its detailed protocol as well as factors that could affect DSS-induced pathology. PMID:24510619

  3. Clinical Features of Ulcerative Colitis in Korea

    PubMed Central

    Park, Seon Mee; Han, Dong Soo; Yang, Suk-Kyun; Hong, Weon-Seon; Min, Young Il

    1996-01-01

    Objectives : This study was conducted to investigate the clinical features of ulcerative colitis in Korea and to evaluate the clinical course after medical therapy. Methods : Symptoms, signs and results of the treatment were retrospectively analyzed in 66 patients (male 32, female 34) diagnosed to have ulcerative colitis at the Asan Medical Center. Results : The median age of the beginning of symptoms was 36 years (range, 14–72). Diarrhea and rectal bleeding were observed in 95.1 and 91.4%, respectively, at the time of diagnosis, while extra-colonic manifestations were observed in 24.1%. In 41 patients (62.1%), colitis developed in the rectum and sigmoid colon, while left colitis and extensive colitis developed in 11 (16.7%) and 14 patients (21.2%), respectively. The severity of disease was determined according to the clinical criteria, resulting in 22 (33.3%) mild, 21 (31.8%) moderate and 23 (34.8%) severe diseases. The seventy was also classified as 1, 2 and 3 by sigmoido-colonoscopic findings: 1;17 patients(25.8%), 2;27(40.9%) and 22(33.3%). Among 23 patients with severe disease, 5 patients (7.6%) received total colectomy due to toxic megacolon, intractability to medical therapy, ileocolic fistula and intestinal stenosis. The severity determined by colonoscopic findings was well correlated with that determined clinically and was closely related to the severity of symptoms, levels of albumin, hemoglobin and the count of leukocyte. The median duration of symptoms before treatment was 4 weeks (range. 11–300). All patients were treated with sulfasalazine and prednisolone. All patients with medical therapy, except 2 patients (96. 7%), obtained clinical remission. The median days required for remission was 14 (range, 3–70). Relapse rates at 6 months, 1 year and 2 years after the initiation of treatment were 19.7, 34.1 and 49.3%, respectively. The median disease-free interval from the time of remission was 10 months (range, 2–60). After remission, the

  4. Colitis amebiasis with symptom of occasional dripped anal bleeding.

    PubMed

    Wandono, Hadi

    2007-01-01

    Colitis amebiasis is usually characterized by bloody and mucous diarrhea, abdominal pain and anal discomfort. However, there is unusual manifestation of colitis amebiasis, such as occasional dripped anal bleeding, which sometimes spouted. Therefore, we often do not suspect such symptoms for colitis amebiasis. Laboratory examination includes complete laboratory test, coagulation and hematologic test, ICT TBC and colonoscopy. The pathology anatomy examination reveals positive results of trophozoites. Treatment by using metronidazole tablet provides good result for this disease.

  5. Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient

    PubMed Central

    Carter, Dan; Olchovsky, David; Pokroy, Russell; Ezra, David

    2006-01-01

    Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment. We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients. PMID:17106945

  6. Fulminant amebic colitis in an HIV-infected homosexual man.

    PubMed

    Ishioka, Haruhiko; Umezawa, Masami; Hatakeyama, Shuji

    2011-01-01

    We present a case of fulminant amebic colitis in a human immunodeficiency virus (HIV)-infected homosexual man. The patient developed colonic perforation over a short time despite empirical therapy with metronidazole, and underwent right hemicolectomy. Amebic colitis was pathologically diagnosed by identifying invasive trophozoites of Entamoeba in a surgical specimen. Amebic colitis is one of the important differential diagnoses of acute abdomen in HIV-infected patients and/or homosexual men, especially in East Asia. Although fulminant amebic colitis is a rare manifestation of amebiasis, early diagnosis and treatment are thought to be important to improve the outcome of this highly fatal complication.

  7. Current Approach to the Evaluation and Management of Microscopic Colitis.

    PubMed

    Cotter, Thomas G; Pardi, Darrell S

    2017-02-01

    Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients' quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis. Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0-24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment. The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.

  8. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    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

  9. Ulcerative Colitis: Update on Medical Management.

    PubMed

    Iskandar, Heba N; Dhere, Tanvi; Farraye, Francis A

    2015-11-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose pathogenesis is multifactorial and includes influences from genes, the environment, and the gut microbiome. Recent advances in diagnosis and treatment have led to significant improvement in managing the disease. Disease monitoring with the use of therapeutic drug monitoring, stool markers, and assessment of mucosal healing have garnered much attention. The recent approval of vedolizumab for treatment of moderate to severe UC has been a welcome addition. Newer biologics, including those targeting the Janus tyrosine kinase (JAK) pathway, are on the horizon to add to the current armamentarium of anti-TNF alpha and anti-integrin therapies. The recent publication of the SCENIC consensus statement on surveillance and management of dysplasia in UC patients supports the use of chromoendoscopy over random biopsies in detecting dysplasia. This review highlights these recent advances along with others that have been made with ulcerative colitis.

  10. Varied Clinical Manifestations of Amebic Colitis.

    PubMed

    Cooper, Chad J; Fleming, Rhonda; Boman, Darius A; Zuckerman, Marc J

    2015-11-01

    Invasive amebiasis is common worldwide, but infrequently observed in the United States. It is associated with considerable morbidity in patients residing in or traveling to endemic areas. We review the clinical and endoscopic manifestations of amebic colitis to alert physicians to the varied clinical manifestations of this potentially life-threatening disease. Copyright ©Most patients present with watery or bloody diarrhea. Less common presentations of amebic colitis include abdominal pain, overt gastrointestinal bleeding, exacerbation of inflammatory bowel disease, or the incidental association with colon cancer. Amebic liver abscesses are the most frequent complication. Rectosigmoid involvement may be found on colonoscopy; however, most case series have reported that the cecum is the most commonly involved site, followed by the ascending colon. Endoscopic evaluation should be used to assist in the diagnosis, with attention to the observation of colonic inflammation, ulceration, and amebic trophozoites on histopathological examination.

  11. Ileal pouch surgery for ulcerative colitis

    PubMed Central

    Bach, Simon P; Mortensen, Neil J

    2007-01-01

    Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure. PMID:17659667

  12. [Non-surgical therapy for ulcerative colitis].

    PubMed

    Asakura, H; Suzuki, K; Honma, T

    1997-04-01

    Ulcerative colitis involving primarily the mucosa of the colon and rectum is a diffuse and nonspecific inflammatory disease. Immunocompetent cells infiltrating in the inflammed mucosa are mainly lymphocytes, macrophages and neutrophils. These activated cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8 and TNF alpha and inflammatory activators such as PAF, leukotriene, prostaglandins, free radicals and proteases, resulting in acute on chronic states. Non-surgical therapy for ulcerative colitis includes basic medical therapy with sulfasulphapyridine, 5-ASA, corticosteroids and immune suppressive drugs as well as new therapies, which are leukocytapheresis, granulocytapheresis, anticytokine therapy with antiTNF alpha monoclonal antibody, IL-1ra and IL-10, intravenous treatment of massive immunoglobulins and transdermal nicotine therapy.

  13. Ulcerative colitis with gastric and duodenal involvement.

    PubMed

    García Gavilán, María Del Carmen; López Vega, María Carmen; Sánchez, Isabel María

    2017-07-01

    Ulcerative colitis is one of the forms of presentation of the inflammatory bowel disease. UC yypically affects the large bowel but in the last few years more cases with proximal involvement have been described (diffuse gastritis, focally enhanced gastritis and duodenitis). We present the case of gastric and duodenitis involvement in the context of a moderate-severe ulcerative pancolitis which showed a good evolution and resolution of symptoms with corticoid treatment.

  14. Ulcerative Colitis - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Ulcerative Colitis - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Traditional (繁體中文) French (français) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (af Soomaali) Spanish (español) ...

  15. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    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. PMID:23091744

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

    PubMed

    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.

  17. Sesame oil accelerates healing of 2,4,6-trinitrobenzenesulfonic acid-induced acute colitis by attenuating inflammation and fibrosis.

    PubMed

    Periasamy, Srinivasan; Hsu, Dur-Zong; Chandrasekaran, Victor Raj Mohan; Liu, Ming-Yie

    2013-09-01

    Sesame oil is a component of traditional health food in Asian countries. Acute colitis is a form of inflammatory bowel disease (IBD) with chronic inflammatory disorder of the bowel. The precise etiology of IBD remains unknown, but it is believed that an abnormal host response to endogenous antigens causes initial tissue injury with amplification of the immune response. We investigated the protective effect of sesame oil against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in rats. Rats were intracolonically instilled with TNBS (120 mg/kg) using a cannula to induce colitis and then orally gavaged with sesame oil (4 mL/kg for 7 days) to attenuate TNBS-induced acute colitis. The acute colitis activity index (ACAI) was assessed using the colon weight/length ratio (mg/cm), thickness, extension of lesion, diarrhea, and macroscopic and microscopic damage scores. In addition, the degree of inflammation, mucins, and fibrosis was assessed by measuring mast cells, CD68(+) cells, neutral mucin, acidic mucin, collagen, and laminin on day 8 after inducing acute colitis. All tested parameters except neutral mucins were significantly higher in TNBS-induced acute colitis. Sesame oil significantly decreased the degree of inflammation, fibrosis, and acidic mucin and increased neutral mucin. We conclude that sesame oil accelerates the healing of an inflamed colon by inhibiting inflammation, acidic mucin, and fibrosis in TNBS-induced acute colitis in rats.

  18. Golimumab for the treatment of ulcerative colitis.

    PubMed

    Flamant, Mathurin; Paul, Stephane; Roblin, Xavier

    2017-07-01

    Tumor necrosis factor antagonists have revolutionized the therapeutic management of inflammatory bowel disease. Infliximab and adalimumab were the first biological agents used to induce and maintain remission in ulcerative colitis. More recently, a third tumor necrosis factor antagonist, golimumab, was approved, extending the therapeutic approach for moderate-to-severe ulcerative colitis. Areas covered: In this review, the authors review the literature on the efficacy and safety of golimumab in the context of other anti-TNF agents used in the treatment of this disease. The role of therapeutic drug monitoring in the case of loss of response to an anti-TNF agent is also discussed. Expert opinion: Golimumab is currently effective to induce and maintain remission in patients with ulcerative colitis, especially those patients who are naive for an anti-TNF agent. No large studies have evaluated the efficacy of golimumab after failure of a first-line TNF antagonist therapy. In the case of loss of response to a first anti-TNF agent, therapeutic drug monitoring is essential to determine the most suitable therapeutic option.

  19. Endogenous prion protein attenuates experimentally induced colitis.

    PubMed

    Martin, Gary R; Keenan, Catherine M; Sharkey, Keith A; Jirik, Frank R

    2011-11-01

    Although the cellular prion protein (PrP(C)) is expressed in the enteric nervous system and lamina propria, its function(s) in the gut is unknown. Because PrP(C) may exert a cytoprotective effect in response to various physiologic stressors, we hypothesized that PrP(C) expression levels might modulate the severity of experimental colitis. We evaluated the course of dextran sodium sulfate (DSS)-induced colitis in hemizygous Tga20 transgenic mice (approximately sevenfold overexpression of PrP(C)), Prnp(-/-) mice, and wild-type mice. On day 7, colon length, disease severity, and histologic activity indices were determined. Unlike DSS-treated wild-type and Prnp(-/-) animals, PrP(C) overexpressing mice were resistant to colitis induction, exhibited much milder histopathologic features, and did not exhibit weight loss or colonic shortening. In keeping with these results, pro-survival molecule expression and/or phosphorylation levels were elevated in DSS-treated Tga20 mice, whereas pro-inflammatory cytokine production and pSTAT3 levels were reduced. In contrast, DSS-treated Prnp(-/-) mice exhibited increased BAD protein expression and a cytokine expression profile predicted to favor inflammation and differentiation. PrP(C) expression from both the endogenous Prnp locus or the Tga20 transgene was increased in the colons of DSS-treated mice. Considered together, these findings demonstrate that PrP(C) has a previously unrecognized cytoprotective and/or anti-inflammatory function within the murine colon.

  20. Novel topical therapies for distal colitis.

    PubMed

    Lawrance, Ian Craig

    2010-10-06

    Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immunosuppressants and the anti-tumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel(®) enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled trials. This review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.

  1. Ulcerative Colitis: A Challenge to Surgeons

    PubMed Central

    Parray, Fazl Q; Wani, Mohd L; Malik, Ajaz A; Wani, Shadab N; Bijli, Akram H; Irshad, Ifat; Nayeem-Ul-Hassan

    2012-01-01

    Ulcerative colitis is a chronic disease that specifically affects the mucosa of the rectum and colon. Although the etiology of this recurring inflammatory disorder remains essentially unknown, there have been significant advances in identifying the likely genetic and environmental factors that contribute to its pathogenesis. The clinical course of the disease typically manifests with remissions and exacerbations characterized by rectal bleeding and diarrhea. Since ulcerative colitis most commonly affects patients in their youth or early middle age, the disease can have serious long-term local and systemic consequences. There is no specific medical therapy that is curative. Although medical therapy can ameliorate the inflammatory process and control most symptomatic flares, it provides no definitive treatment for the disease. Proctocolectomy or total removal of the colon and rectum provides the only complete cure; however, innovative surgical alternatives have eliminated the need for a permanent ileostomy. The aim of this review is to provide a detailed account of the surgical management of ulcerative colitis. PMID:23189226

  2. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

    PubMed

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A; Yaylali, Asl; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments.

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

    PubMed Central

    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

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS 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. RESULTS 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 < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation. PMID:27672276

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

    PubMed

    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 < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.

  5. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    PubMed

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  6. Deoxyschizandrin Suppresses DSS-Induced Ulcerative Colitis in Mice

    PubMed Central

    Zhang, Wen-feng; Yang, Yan; Su, Xin; Xu, Da-yan; Yan, Yu-li; Gao, Qiao; Duan, Ming-hua

    2016-01-01

    Background/Aims: Deoxyschizandrin as one of the most important component of Schisandra chinensis (Turcz.) Baill plays an immunomodulatory role in a variety of diseases, yet its role in ulcerative colitis remains to be elucidated. We aimed to investigate the role of deoxyschizandrin in DSS-induced ulcerative colitis in mice. Patients and Methods: In the present study, an inflammation model of cells was constructed to confirm the anti-inflammatory effect of deoxyschizandrin. Then a mouse model with Dextran sulfate sodium sulfate (DSS)-induced ulcerative colitis was constructed, and the effects of deoxyschizandrin on mouse colon inflammation, apoptosis, and CD4 T lymphocyte infiltration in ulcerative colitis were examined. Result: Deoxyschizandrin could improve the symptoms of ulcerative colitis, determined by hematoxylin-eosin (HE) staining and histopathological scores. Moreover, deoxyschizandrin reduced the levels of inflammatory cytokines, suppressed CD4 T cell infiltration, and effectively inhibited apoptosis in the colon of DSS-induced ulcerative colitis mice. Conclusion: In summary, deoxyschizandrin can effectively rescue the symptoms of DSS-induced ulcerative colitis in mice by inhibiting inflammation. T cell infiltration and apoptosis in the colon, suggesting that deoxyschizandrin could be a potential drug in treating ulcerative colitis. PMID:27976641

  7. Acute ischaemic colitis associated with oral phenylephrine decongestant use.

    PubMed

    Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M

    2014-06-03

    In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients' use of OTC and prescribed medications.

  8. Temporal comorbidity of mental disorder and ulcerative colitis.

    PubMed

    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.

  9. Acute rectocolitis following endoscopy in health check-up patients--glutaraldehyde colitis or ischemic colitis?

    PubMed

    Hsu, Chao-Wen; Lin, Chieh-Hsin; Wang, Jui-Ho; Wang, Hsin-Tai; Ou, Wen-Chieh; King, Tai-Ming

    2009-10-01

    Acute rectocolitis is a rare complication that follows endoscopy. It could be caused by glutaraldehyde or ischemic injury. The clinical, endoscopic, radiological, and pathological features of glutaraldehyde-induced colitis may mimic those of ischemic colitis. We reported our experiences regarding this problem. The medical records of patients with acute rectocolitis following endoscopy treated at Kaohsiung Veterans General Hospital since 2001 were reviewed. The indication of endoscopy was health check-up for all patients. Published English-language studies regarding acute rectocolitis following endoscopy were also reviewed. An outbreak of six patients occurred in April 2002 and one cirrhotic patient was admitted in July 2008. All patients developed a self-limited syndrome of abdominal pain and bloody diarrhea within 48 h of uncomplicated endoscopy. One severely ill patient required hospitalization to receive intravenous fluid and antibiotics. After the investigation in April 2002, glutaraldehyde-induced colitis was diagnosed due to a defect in the endoscope-cleansing procedure. There were no any deficiencies in the cleansing procedure in July 2008. Considering the patient's concomitant disease, we postulated that ischemic colitis with cirrhosis-related intestinal inflammation and endotoxemia was the possible diagnosis in this sporadic case. Endoscopists should be aware of this iatrogenic complication in patients presenting with acute rectocolitis, especially in those who have undergone recent endoscopic examination. An outbreak of acute rectocolitis following endoscopy should be considered glutaraldehyde-induced and should lead to an investigation of cleansing and equipment-disinfection procedures. In the absence of strong evidence of an outbreak, an infectious disease, or contamination of glutaraldehyde, a sporadic case should be considered ischemic colitis especially in patients with relevant concomitant diseases or predisposing factors.

  10. Ulcerative colitis: current and future treatment strategies.

    PubMed

    Lissner, Donata; Siegmund, Britta

    2013-01-01

    Since the incidence of inflammatory bowel diseases including ulcerative colitis is continuously increasing worldwide, there is a strong need for effective treatment strategies. However, there is no therapy allowing for healing ulcerative colitis; consequently, the available medications will have to be applied at their best. The preferred option for mild pan- or left-sided colitis is still mesalazine. One can only emphasize that the formulations allowing for once daily dosing are not only equally effective, but even facilitate the implication of long-term therapy in daily life. In case steroids are frequently required to control disease, further immunosuppressive therapy should be introduced in order to minimize steroid exposure. Thiopurines represent the first-choice immunosuppressive medication. In more severe cases, early escalation to combinatory therapies with anti-TNF antibodies should be considered with the possibility of therapy deescalation after induction of remission. Major difficulties arise with steroid-refractory acute flares. Here cyclosporine as well as anti-TNF strategies can be initiated. However, in case of severe disease, the high 1-year colectomy rate of about 50% should be considered. If short-term surgery is an option due to disease severity, cyclosporine might be advantageous since the half-life is short compared to infliximab or adalimumab. The central problem of all therapeutic approaches is that because we chase after the disease, solid markers that allow for prediction of the future disease course are desirable. In fact, the CD8+ transcriptome might fill this gap and will potentially lead to the classification of patients in low- and high-risk groups. Copyright © 2013 S. Karger AG, Basel.

  11. Nodular colitis: endoscopic image an unusual finding.

    PubMed

    Loza Vargas, L A; Núñez Rodríguez, Henar; Benito Sanz, Marina; Zamora Martínez, Tomás; Díez Redondo, Pilar; Pérez Miranda, Manuel

    2016-10-01

    An 82-year-old male with a history of high blood pressure, COPD, chronic myeloid leukemia, and stage-4 chronic renal failure. Admitted to hospital for lower-limb cellulitis and severe COPD exacerbation, he received antibiotic therapy and bronchodilators. During his hospital stay he developed severe anemia and had an hematochezia event with no diarrhea. A complete colonoscopy found small (4-7 mm) nacreous elevated lesions, circumferential in shape, in the cecum and ascending colon with some bleeding stigmata and submucosal bleeding suggestive of infectious colitis; stool culture was negative and Clostridium difficile toxins were positive. The condition was histologically confirmed.

  12. [Treatment of microscopic colitis - what's new?

    PubMed

    Gonciarz, Maciej; Szkudłapski, Dawid; Eszyk, Jerzy; Smagacz, Justyna; Kopała, Marek

    2016-10-19

    Microscopic colitis (MC) is frequent, although still uncommonly diagnosed, cause of chronic diarrhea. The etiopathology of MC is unknown but this disease has strong influence on patient's quality of life (measured by health-related quality of life - HRQoL). MC is characterized by microscopic abnormalities in large bowel's mucosa whereas endoscopic and radiological examination findings are normal. The treatment of MC is an essential social and financial problem due to its frequency in society. Thanks to the results of some controlled research which judged efficiency of some medicines as well as advisory groups recommendations, the MC therapy is nowadays going from empiric to accordance with evidence based medicine.

  13. Minimally invasive screening for colitis using attenuated total internal reflectance fourier transform infrared spectroscopy.

    PubMed

    Titus, Jitto; Viennois, Emilie; Merlin, Didier; Unil Perera, A G

    2017-03-01

    This article describes a rapid, simple and cost-effective technique that could lead to a screening method for colitis without the need for biopsies or in vivo measurements. This screening technique includes the testing of serum using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy for the colitis-induced increased presence of mannose. Chronic (Interleukin 10 knockout) and acute (Dextran Sodium Sulphate-induced) models for colitis are tested using the ATR-FTIR technique. Arthritis (Collagen Antibody Induced Arthritis) and metabolic syndrome (Toll like receptor 5 knockout) models are also tested as controls. The marker identified as mannose uniquely screens and distinguishes the colitic from the non-colitic samples and the controls. The reference or the baseline spectrum could be the pooled and averaged spectra of non-colitic samples or the subject's previous sample spectrum. This shows the potential of having individualized route maps of disease status, leading to personalized diagnosis and drug management.

  14. Inverse Association Between Helicobacter pylori Gastritis and Microscopic Colitis.

    PubMed

    Sonnenberg, Amnon; Genta, Robert M

    2016-01-01

    Inflammatory bowel disease is known to be inversely associated with Helicobacter pylori infection of the upper gastrointestinal tract. We hypothesized that a similar inverse association also applied to microscopic colitis. The associations between microscopic colitis and presence of H. pylori-positive chronic active gastritis (CAG), H. pylori-negative CAG, intestinal metaplasia, or gastric atrophy were expressed as odds ratios with their 95% confidence intervals. Multivariate logistic regression analyses were used to adjust these associations for sex, age, percentage residents per ZIP code with white, black, Hispanic, or Asian ethnicity, percentage with college education, average housing values, annual income, and population size of individual ZIP codes. H. pylori-positive CAG was less common among patients with than without microscopic colitis (odds ratio = 0.61; 95% confidence interval, 0.52-0.70). Intestinal metaplasia also occurred less frequently among patients with than without microscopic colitis (0.75, 0.65-0.86). These inverse associations remained unaffected by adjustments for parameters of ethnicity and socioeconomic status. In contradistinction with H. pylori-positive CAG, H. pylori-negative CAG was more common in patients with than without microscopic colitis (1.54, 1.17-1.97). H. pylori infection and microscopic colitis are inversely associated. This observation is consistent with similar inverse associations found between H. pylori and inflammatory bowel disease. These relationships may provide clues about the yet unknown etiology of microscopic colitis.

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

    PubMed

    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 < 0.001). Jewish patients with microscopic colitis were slightly older than the reference group (65.6 ± 13.4 years, P = 0.015). Compared with the reference group (prevalence = 1.20%), microscopic colitis was significantly less common among patients of Indian (prevalence = 0.28%, odds ratio = 0.32, 95% confidence interval = 0.13-0.65), East Asian (0.22%, 0.19, 0.14-0.26), or Hispanic decent (0.48%, 0.40, 0.36-0.45) and significantly more common among Jewish patients (1.30%, 1.10, 1.01-1.21). Microscopic colitis shows striking variations of its occurrence among different ethnic groups. Such variations could point at differences in the exposure to environmental risk factors.

  16. Obstructive ileus caused by phlebosclerotic colitis

    PubMed Central

    Lee, Seung Hyun; Park, Se Jin; Heo, Ju Yeol; Paik, Woo Hyun; Bae, Won Ki; Kim, Nam-Hoon; Kim, Kyung-Ah; Lee, June Sung

    2016-01-01

    A 57-year-old man with chronic kidney disease and a history of using numerous herbal medications visited Inje University Ilsan Paik Hospital for abdominal pain and vomiting. An abdominal radiograph showed diffuse small bowel distension containing multiple air-fluid levels and extensive calcifications along the colon. Computed tomography showed colon wall thickening with diffuse calcification along the colonic mesenteric vein and colonic wall. Colonoscopy, performed without bowel preparation, showed bluish edematous mucosa from the transverse to the distal sigmoid colon, with multiple scar changes. At the mid transverse colon, a stricture was noted and the scope could not pass through. A biopsy of the stricture site revealed nonspecific changes. The patient was diagnosed with phlebosclerotic colitis. After the colonoscopy, the obstructive ileus spontaneously resolved, and the patient was discharged without an operation. Currently, after 2 months of follow-up, the patient has remained asymptomatic. Herein, we report the rare case of an obstructive ileus caused by phlebosclerotic colitis with a colon stricture. PMID:27799889

  17. IN VITRO STUDIES OF ULCERATIVE COLITIS

    PubMed Central

    Perlmann, Peter; Broberger, Ove

    1963-01-01

    Freshly isolated fetal human colon cells were labeled with 32P-orthophosphate or 14C-amino acids and exposed to white blood cells from children with ulcerative colitis or from healthy controls. Exposure of the colon cells to patients' white cells led to a rapid isotope release, significantly higher than that obtained with normal white cells. After 150 minutes of incubation, 75 per cent of the total isotope present was found in the media of the colitis samples but only 40 per cent in those of the controls. Consistent results were obtained with white blood cells from 14 patients and 18 healthy individuals. Similar results were obtained with either fresh white cells or with white cells aged for 12 to 18 hours and consisting to 60 to 70 per cent of lymphocytes and to 20 to 30 per cent of large mononuclear cells. No specific cytotoxic activity could be conferred onto normal white cells by pretreating them with patients' serum containing antibodies against colon antigen. The cytotoxic action of the patients' white cells was immunologically specific, since no difference from the controls was found in the isotope release when cells from other organs or animals were similarly treated. Preliminary experiments suggested that the patients' white cells could be desensitized by pretreating them with colon extract. For obtaining a significant cytotoxic effect of the patients' white cells, the presence of 10 to 20 per cent of fresh guinea pig or human serum in the incubation medium was required. PMID:13942482

  18. Prebiotics and synbiotics in ulcerative colitis.

    PubMed

    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.

  19. Severe ischemic colitis following olanzapine use - A case report.

    PubMed

    Fernandes, Samuel R; Alves, Rosa; Araújo Correia, Luís; Rita Gonçalves, Ana; Malaquias, João; Oliveira, Emilia; Velosa, José

    2016-09-01

    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.

  20. Elective and emergent operative management of ulcerative colitis.

    PubMed

    Metcalf, Amanda M

    2007-06-01

    Surgical therapy of ulcerative colitis is effective, safe, and provides an improved quality of life in those whose disease cannot be managed medically. In the elective setting, widespread acceptance of restorative proctocolectomy has made surgical therapy an attractive option in the overall management of ulcerative colitis. Enthusiasm for this procedure should be tempered by the acknowledgment of the significant incidence of pouchitis in the long term, however. Proctocolectomy with ileostomy remains a good surgical option for patients who are unsuitable for restorative procedures. The standard therapy for fulminant colitis or toxic megacolon remains subtotal colectomy with ileostomy. Patients undergoing subtotal colectomy are candidates for conversion to restorative procedures.

  1. Budesonide-Related Iatrogenic Cushing's Syndrome in Microscopic Colitis.

    PubMed

    Tripathi, Kartikeya; Dunzendorfer, Thomas

    2017-01-01

    Budesonide is the treatment of choice for microscopic colitis because of its excellent risk to benefit ratio. It is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. It has fewer corticosteroid-related adverse effects than prednisone, and adrenal suppression is considered to be rare. We present a middle-aged woman with lymphocytic colitis whose symptoms responded to budesonide but developed budesonide-related iatrogenic Cushing's syndrome. Withdrawal of budesonide led to restoration of normal pituitary-adrenal responsiveness but at the price of recurrent diarrhea due to re-emergence of lymphocytic colitis.

  2. [The potentials of echography in the diagnosis of chronic colitis].

    PubMed

    Tarasiuk, B A; Tkach, S M; Klymenko, O P; Babko, S O; Denysova, M F

    1994-01-01

    Ultrasonic signs of colitis were studied in 24 adults aged 20 to 53 yr and 38 children aged 3-16 yr in whom chronic colitis was diagnosed. 2 adults and three children had ulcerative colitis. The results obtained showed that with the aid of echography it is possible to detect inflammatory lesions in the large intestine as well as to observe the time course of changes in its wall during the course of treatment. Ultrasonic investigation can be of screening type in detecting an inflammatory process in the large intestine, on the one hand, and a method of profound study of changes in its wall, on the other.

  3. Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group.

    PubMed

    Fernández-Bañares, F; Casanova, M J; Arguedas, Y; Beltrán, B; Busquets, D; Fernández, J M; Fernández-Salazar, L; García-Planella, E; Guagnozzi, D; Lucendo, A J; Manceñido, N; Marín-Jiménez, I; Montoro, M; Piqueras, M; Robles, V; Ruiz-Cerulla, A; Gisbert, J P

    2016-02-01

    Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. To develop an evidence-based clinical practice guide on MC current concepts. Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence. © 2015 John Wiley & Sons Ltd.

  4. Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study.

    PubMed

    Wickbom, Anna; Nyhlin, Nils; Montgomery, Scott M; Bohr, Johan; Tysk, Curt

    2017-05-01

    Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited. The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis. A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality. Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001). Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

  5. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

    PubMed

    Gkouskou, K K; Ioannou, M; Pavlopoulos, G A; Georgila, K; Siganou, A; Nikolaidis, G; Kanellis, D C; Moore, S; Papadakis, K A; Kardassis, D; Iliopoulos, I; McDyer, F A; Drakos, E; Eliopoulos, A G

    2016-05-12

    In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

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

    PubMed Central

    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

  7. Ulcerative colitis in the United States Army in 1944

    PubMed Central

    Nefzger, M. Dean; Acheson, E. D.

    1963-01-01

    This paper compares the mortality of 525 men admitted to U.S. Army hospitals in 1944 with ulcerative colitis compared with 518 controls matched for age, race, and rank. The excess mortality in the ulcerative colitis group as compared with the control group was due to approximately equal proportions of deaths from ulcerative colitis (2·9%) and cancer of the caecum, colon, and rectum (3·2%). The mortality from ulcerative colitis occurred mainly in the first and immediately subsequent years after diagnosis while most of the deaths from cancer occurred in later years. A striking correlation is shown between bad prognosis and the extent of radiological involvement of the colon in 1944. PMID:13937910

  8. Ulcerative Colitis in University Students (A 20 Year Interim Report)

    ERIC Educational Resources Information Center

    Ray, Mary M.

    1970-01-01

    In order to give students with colitis the best chance of completing school, a very close relationship between previous physicians and student health services, and university physicians and consulting gastroenterologists must be developed. (Author)

  9. Fulminant ulcerative colitis complicated by treatment-refractory bacteremia

    PubMed Central

    Krease, Michael; Stroup, Jeff; Som, Mousumi

    2016-01-01

    Severe ulcerative colitis is defined by more than six bloody stools daily and evidence of toxicity, demonstrated by fever, tachycardia, anemia, or an elevated erythrocyte sedimentation rate. Fulminant disease represents a subset of severe disease with signs and symptoms suggestive of increased toxicity. Treatment of severe colitis includes intravenous corticosteroid administration, with consideration of intravenous infliximab 5 mg/kg. Failure to show improvement after 3 to 5 days is an indication for colectomy or treatment with intravenous cyclosporine. We report a 23-year-old Hispanic woman with decompensated cirrhosis presenting with new-onset fulminant ulcerative colitis and resulting polymicrobial bacteremia, requiring colectomy for infection source control and colitis treatment. PMID:27695178

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

    MedlinePlus

    ... Back Crohn’s Disease & Ulcerative Colitis: A Guide for Parents Email Print + Share You recently learned that your ... are uncovering the culprits involved in IBD, and technology is making it possible to target them and ...

  11. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    PubMed

    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.

  12. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity

    PubMed Central

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

    2014-01-01

    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. PMID:24707159

  13. Mindfulness May Be Helpful for People with Ulcerative Colitis

    MedlinePlus

    ... similar in format but did not include coping skills, practice, or any information on ulcerative colitis. Participants were assessed at the study’s start, shortly after completion of the 8-week ...

  14. Primary ileal villous atrophy is often associated with microscopic colitis

    PubMed Central

    Marteau, P; Lavergne-Slove, A; Lemann, M; Bouhnik, Y; Bertheau, P; Becheur, H; Galian, A; Rambaud, J

    1997-01-01

    Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis. 

 Keywords: intestinal villous atrophy; ileum; secretory diarrhoea; bile acid malabsorption; microscopic colitis PMID:9391260

  15. Ulcerative Colitis in University Students (A 20 Year Interim Report)

    ERIC Educational Resources Information Center

    Ray, Mary M.

    1970-01-01

    In order to give students with colitis the best chance of completing school, a very close relationship between previous physicians and student health services, and university physicians and consulting gastroenterologists must be developed. (Author)

  16. Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease.

    PubMed

    Rhodes, J M; Gallimore, R; Elias, E; Allan, R N; Kennedy, J F

    1985-08-01

    Because the normal faecal flora includes bacteria which can produce mucus-digesting glycosidases, it follows that increased digestion of colonic mucus by these bacterial enzymes could be important in the pathogenesis of ulcerative colitis. Faecal activities of potential mucus-degrading glycosidases have therefore been assayed in samples from patients with inflammatory bowel disease and normal controls. The enzymes alpha-D-galactosidase, beta-D-galactosidase, beta-NAc-D-glucosaminidase alpha-L-fucosidase and neuraminidase were assayed. Considerable glycosidase activity was present in most faecal samples. Similar activities of all the enzymes assayed were found in faeces from patients with ulcerative colitis, Crohn's disease and normal controls and there was no significant correlation with disease activity. These results imply that relapse of ulcerative colitis is not initiated by increased degradation of colonic mucus by faecal glycosidases but do not exclude a role for bacterial mucus degradation in the pathogenesis of ulcerative colitis.

  17. The effect of menthol on acute experimental colitis in rats.

    PubMed

    Ghasemi-Pirbaluti, Masoumeh; Motaghi, Ehsan; Bozorgi, Homan

    2017-03-18

    Menthol is an aromatic compound with high antiinflammatory activity. The purpose of the current research is to investigate the effectiveness of menthol on acetic acid induced acute colitis in rats. Animals were injected with menthol (20 and 50 and 80mg/kg, i.p.) 24h prior to induction of colitis for 3 consecutive days. Menthol at medium and higher doses similar to dexamethasone as a reference drug significantly reduced body weight loss, macroscopic damage score, ulcer area, colon weight, colon length and improved hematocrit in rats with colitis. The histopathological examination also confirmed anti-colitic effects of menthol. Menthol also reduced significantly the colonic levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and myeloperoxidase (MPO) activity in inflamed colons. Thus, the findings of the current study provide evidence that menthol may be beneficial in patients suffering from acute ulcerative colitis.

  18. Bifidobacterium infantis attenuates colitis by regulating T cell subset responses

    PubMed Central

    Zuo, Li; Yuan, Kai-Tao; Yu, Li; Meng, Qing-Hong; Chung, Peter Chee-Keung; Yang, Ding-Hua

    2014-01-01

    AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice. METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs) were detected by flow cytometry and real-time RT-PCR. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in MLNs and histological changes of colonic tissue were examined 6 d after colitis induction. RESULTS: No significant change in cytokine profiles was observed in normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN-γ, IL-12p40), Th17-related transcription factor and cytokines (RORγt, IL-21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis. Furthermore, flow cytometry assay showed B. infantis increased the numbers of CD4+Foxp3+ Tregs and Th17 cells in MLNs. Colitis was successfully induced by TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17 responses. Feeding high dose B. infantis for 3 wk before colitis induction decreased the inflammatory cell infiltration and goblet cell depletion and restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1-related cytokines (T-bet, IL-2 and IFN-γ) and Th17-related cytokines (IL-12p40, RORγt, IL-17A, IL-21 and IL-23), and increased Treg-related molecules (Foxp3, IL-10 and TGF-β) in colitis mice. CONCLUSION: B. infantis effectively attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and increasing Foxp3+ Treg response in the colonic mucosa. PMID:25561798

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

    AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: 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 15th 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. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th 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 6th 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

  1. Proctocolectomy without ileostomy for ulcerative colitis.

    PubMed Central

    Parks, A G; Nicholls, R J

    1978-01-01

    An operation has been developed that permits total removal of all disease-prone mucosa in ulcerative colitis but avoids the need for a permanent ileostomy. The colon and upper half of the rectum are excised and the remaining inflamed mucosa is stripped from the rectal stump down to the dentate line of the anal canal. A pouch is fashioned from a triplicated loop of terminal ileum. This is drawn down through the denuded rectum and an anastomosis created, via the per-anal approach, between the ileum just distal to the pouch and the mid-anal canal. A temporary ileostomy is made. Out of eight patients so treated, five were available for assessment, and four of them were highly satisfied with the result in improved health and function. The remaining three were awaiting closure of their ileostomies. Images FIG 3 PMID:667572

  2. Stercoral colitis: diagnostic value of CT findings

    PubMed Central

    Ünal, Emre; Onur, Mehmet Ruhi; Balcı, Sinan; Görmez, Ayşegül; Akpınar, Erhan; Böge, Medine

    2017-01-01

    PURPOSE We aimed to evaluate the CT findings of stercoral colitis (SC). METHODS Forty-one patients diagnosed with SC between February 2006 and April 2015 were retrospectively reviewed. RESULTS Rectosigmoid colon was the most frequently involved segment (100%, n=41). CT findings can be summarized as follows: dilatation >6 cm and wall thickening >3 mm of the affected colon segment (100%, n=41), pericolonic fat stranding (100%, n=41), mucosal discontinuity (14.6 %, n=6), presence of free air (14.6%, n=6), free fluid (9.7%, n=4), and pericolonic abscess (2.4%, n=1). The sign most related with mortality was the length of the affected colon segment >40 cm. CONCLUSION CT has an important role in SC, since life-threatening complications can be easily revealed by this imaging modality. Increased length of involved colon segment (>40 cm) is more likely to be associated with mortality. PMID:27910814

  3. Idiopathic myelofibrosis associated with ulcerative colitis.

    PubMed

    Arellano-Rodrigo, Eduardo; Esteve, Jordi; Giné, Eva; Panés, Julián; Cervantes, Francisco

    2002-07-01

    A patient with ulcerative colitis (UC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of UC was established by colonoscopy and large bowel biopsy, performed after a one-month history of abdominal pain and bloody diarrhea. The patient showed a favorable response to prednisone and mesalamine treatment and six months later he developed a new episode of UC, which was successfully controlled with treatment. However, two years later splenomegaly and anemia were observed, with aniso-poikilocytosis, tear-drop cells, immature myeloid precursors in the peripheral blood, and increased serum LDH, arising the suspicion of IM, a diagnosis that was confirmed by bone marrow biopsy. The present case represents a new association of IM with an autoimmune disease and gives support to the hypothesis of a possible immune basis of some IM cases.

  4. Colitis detection on abdominal CT scans by rich feature hierarchies

    NASA Astrophysics Data System (ADS)

    Liu, Jiamin; Lay, Nathan; Wei, Zhuoshi; Lu, Le; Kim, Lauren; Turkbey, Evrim; Summers, Ronald M.

    2016-03-01

    Colitis is inflammation of the colon due to neutropenia, inflammatory bowel disease (such as Crohn disease), infection and immune compromise. Colitis is often associated with thickening of the colon wall. The wall of a colon afflicted with colitis is much thicker than normal. For example, the mean wall thickness in Crohn disease is 11-13 mm compared to the wall of the normal colon that should measure less than 3 mm. Colitis can be debilitating or life threatening, and early detection is essential to initiate proper treatment. In this work, we apply high-capacity convolutional neural networks (CNNs) to bottom-up region proposals to detect potential colitis on CT scans. Our method first generates around 3000 category-independent region proposals for each slice of the input CT scan using selective search. Then, a fixed-length feature vector is extracted from each region proposal using a CNN. Finally, each region proposal is classified and assigned a confidence score with linear SVMs. We applied the detection method to 260 images from 26 CT scans of patients with colitis for evaluation. The detection system can achieve 0.85 sensitivity at 1 false positive per image.

  5. Fulminant amebic colitis: a study of six cases.

    PubMed

    Nisheena, R; Ananthamurthy, Anuradha; Inchara, Y K

    2009-01-01

    Amebic colitis although common, rarely presents as fulminant colitis which has a high morbidity and mortality unless treated promptly and appropriately. To study the clinical, morphological features and outcome of fulminant amebic colitis (FAC). A retrospective study of six patients who underwent surgical resections from 2002-06 and were diagnosed with FAC, was carried out. The morphological features assessed included the average number of trophozoites per high-power field and the depth of invasion of trophozoites into the muscularis propria. The study included five adults and one child who underwent surgery for fulminant colitis. Interestingly, a definite preoperative diagnosis of amebic colitis was made only in one patient and suspected in another. Intraoperatively, multiple perforations of the intestine with peritonitis were the most common findings. Gross examination typically revealed multiple ulcers with exudate and intervening normal mucosa. Microscopically, ulceration and myonecrosis with trophozoites within the exudate were seen in all cases. Trophozoites invading the muscularis propria were seen in five cases. Of the cases that showed myoinvasion by trophozoites, two patients expired within two weeks of surgery. One of the patients who expired also showed co-infection with Actinomyces. FAC is an uncommon outcome in amebic colitis with a high mortality requiring prompt surgical intervention.

  6. The role of CXCR3 in DSS-induced colitis.

    PubMed

    Chami, Belal; Yeung, Amanda W S; van Vreden, Caryn; King, Nicholas J C; Bao, Shisan

    2014-01-01

    Inflammatory bowel disease (IBD) is a group of disorders that are characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the aetiopathogenesis is poorly understood, it is widely believed that IBD stems from a dysregulated immune response towards otherwise harmless commensal bacteria. Chemokines induce and enhance inflammation through their involvement in cellular trafficking. Reducing or limiting the influx of these proinflammatory cells has previously been demonstrated to attenuate inflammation. CXCR3, a chemokine receptor in the CXC family that binds to CXCL9, CXCL10 and CXCL11, is strongly overexpressed in the intestinal mucosa of IBD patients. We hypothesised that CXCR3 KO mice would have impaired cellular trafficking, thereby reducing the inflammatory insult by proinflammatory cell and attenuating the course of colitis. To investigate the role of CXCR3 in the progression of colitis, the development of dextran sulfate sodium (DSS)-induced colitis was investigated in CXCR3-/- mice over 9 days. This study demonstrated attenuated DSS-induced colitis in CXCR3-/- mice at both the macroscopic and microscopic level. Reduced colitis correlated with lower recruitment of neutrophils (p = 0.0018), as well as decreased production of IL-6 (p<0.0001), TNF (p = 0.0038), and IFN-γ (p = 0.0478). Overall, our results suggest that CXCR3 plays an important role in recruiting proinflammatory cells to the colon during colitis and that CXCR3 may be a therapeutic target to reduce the influx of proinflammatory cells in the inflamed colon.

  7. Activation of the Renin-Angiotensin System Promotes Colitis Development

    PubMed Central

    Shi, Yongyan; Liu, Tianjing; He, Lei; Dougherty, Urszula; Chen, Li; Adhikari, Sarbani; Alpert, Lindsay; Zhou, Guolin; Liu, Weicheng; Wang, Jiaolong; Deb, Dilip K.; Hart, John; Liu, Shu Q.; Kwon, John; Pekow, Joel; Rubin, David T.; Zhao, Qun; Bissonnette, Marc; Li, Yan Chun

    2016-01-01

    The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type controls. Treatment with aliskiren (a renin inhibitor), but not hydralazine (a smooth muscle relaxant), ameliorated colitis in RenTgMK mice, although both drugs normalized blood pressure. Chronic infusion of angiotensin II into wild-type mice mimicked the severe colitic phenotype of RenTgMK mice, and treatment with losartan [an angiotensin type 1 receptor blocker (ARB)] ameliorated colitis in wild-type mice, confirming a colitogenic role for the endogenous RAS. In human biopsies, pro-inflammatory cytokines were suppressed in patients with inflammatory bowel disease who were on ARB therapy compared to patients not receiving ARB therapy. These observations demonstrate that activation of the RAS promotes colitis in a blood pressure independent manner. Angiotensin II appears to drive colonic mucosal inflammation by promoting intestinal epithelial cell apoptosis and mucosal TH17 responses in colitis development. PMID:27271344

  8. [Ulcerative colitis and eosinophilic corpus gastritis].

    PubMed

    Nagy, Ferenc; Molnár, Tamás; F Kiss, Zsuzsanna; Tiszlavicz, László; Lonovics, János

    2004-10-31

    Ulcerative colitis seldom associated with nutritive and/or salicylate allergy. Authors present a case of both allergic events at the course of the disease. In 1996 a 19-year-old girl was referred with a history of blood in stool as well as diarrhoea, suggesting ulcerative proctitis. Biopsy revealed ulcerative colitis of the rectum mucosa with eosinophilic infiltration and 20% peripheral eosinophilia was found. Allergic origin and worm infection were ruled out, and after tinidazol treatment, four year elapsed without any signs or symptoms. In December 2000 blood in stools and upper abdominal complaints developed without peripheral eosinophilia. Gastroscopy and biopsy showed a mild chronic gastritis. Olsalazine, budesonide enema and famotidin treatment were started, but then later changed to mesalazine and pantoprazol, because of the constant stomach complaints. The next five months passed without any symptoms. The patient had to break off her seashore journey in July 2000 because of stomach complaints, vomiting and exsiccosis. Peripheral eosinophilia (27.3%) was evident. Gastroscopy revealed erosive ulcers and the biopsy showed eosinophilic gastritis. Biopsies from the jejunum, duodenum and antrum as well as enteroscopy and biopsies from the rectum showed mild eosinophilic infiltration. An allergy test proved the presence of IgE against salicylate, egg protein, seafood protein and the lymphocyte transformation test was also positive against salicylate. Oral food challenges proved to be negative and the amino-salicylate treatment was stopped. After a temporary symptom free period, bloody stools reappeared in May 2003; the peripheral eosinophilia still existed, but had decreased (22.2%). Esomeprazol, and methyl-prednisolone containing enema (40 mg/day/2 weeks) followed by budesonide enema twice a week resulted in a symptom free period and peripheral eosinophilia became almost normalised (6.2%). The authors report a case having ulcerative proctitis first, than

  9. Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.

    PubMed

    Kashima, Shin; Fujiya, Mikihiro; Konishi, Hiroaki; Ueno, Nobuhiro; Inaba, Yuhei; Moriichi, Kentaro; Tanabe, Hiroki; Ikuta, Katsuya; Ohtake, Takaaki; Kohgo, Yutaka

    2015-08-01

    Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Acute experimental distal colitis alters colonic transit in rats.

    PubMed

    Myers, B S; Dempsey, D T; Yasar, S; Martin, J S; Parkman, H P; Ryan, J P

    1997-04-01

    Data from humans with active distal colitis suggest that the proximal colon exhibits increased contractile activity and delayed transit, whereas the distal colon shows decreased contractile activity and rapid transit. The present study used the acetic acid rat model of experimental colitis to determine the effect of distal colitis on total and regional colonic transit in vivo and on the in vitro contractility of circular smooth muscle from the proximal and distal colon. Distal colitis was induced in rats by intracolonic administration of 4% acetic acid; sham control rats received saline enemas. Control and colitic rats were studied 2 days postenemas. Total colon transit was determined by calculating the geometric center of distribution of a radiolabeled marker (51Cr) instilled into the proximal colon. Regional transit was assessed by expressing the radioactivity in the cecum, proximal and distal colon, and excreted stool as a percent of total radioactivity. Muscle strips from the proximal and distal colon were stimulated with 100 microM acetylcholine (ACh) and 60 mM KCl and the tension was expressed as kilograms per square centimeter. Distal colitis was characterized by decreased total colon transit, increased retention of marker in the cecum and proximal colon, and decreased retention of marker in the distal colon. In vitro contractility studies revealed that distal colitis increased proximal colon circular smooth muscle contractility and decreased distal colon circular smooth muscle contractility to both ACh and potassium. Distal colitis is associated with regional differences in colonic circular smooth muscle contractility, which may contribute to delayed transit in the proximal colon and rapid transit in the distal colon.

  12. A practical guide to the management of distal ulcerative colitis.

    PubMed

    Ardizzone, S; Bianchi Porro, G

    1998-04-01

    This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5-aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel drugs for the treatment of distal ulcerative colitis. Short cycles of traditional, rectally administered corticosteroids (methylprednisolone, betamethasone, hydrocortisone) are effective for the treatment of mild to moderately active distal ulcerative colitis. In this context, their systemic administration is limited to patients who are refractory to either oral 5-amino-salicylates, topical mesalazine or topical corticosteroids. Of no value in maintaining remission, the long term use of either or topical corticosteroids may be hazardous. A new class of topically acting corticosteroids [budesonide, fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate, tixocortol (tixocortol pivalate)] represents a valid alternative for the treatment of active ulcerative colitis, and may be useful in the treatment of refractory distal ulcerative colitis. Although there is controversy concerning dosage or duration of therapy, oral and topical mesalazine is effective in the treatment of mild to moderately active distal ulcerative colitis. Sulfasalazine and mesalazine remain the first-choice drugs for the maintenance therapy of distal ulcerative colitis. Evidence exists showing a trend to a higher remission rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or enemas) also is effective in maintenance treatment. For patients with chronically active or corticosteroid-dependent disease, azathioprine and mercaptopurine are effective in reducing either the need for corticosteroids or clinical relapses. Moreover, they are effective for long term maintenance remission. Cyclosporin may be useful in inducing remission in patients with acutely severe disease who do not achieve remission with an intensive intravenous regimen. Existing data suggest that azathioprine and mercaptopurine may

  13. Two gastrointestinal conditions with similar symptoms and endoscopic appearance: irritable bowel syndrome and microscopic colitis.

    PubMed

    Şimşek, Zahide; Tuncer, Nazife Candan; Alagüzlü, Hakan; Karaahmet, Fatih; Çoban, Şahin; Dursun, Ayşe

    2015-01-01

    Irritable bowel syndrome (IBS) is a gastrointestinal condition characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any organic cause. This trial investigated the presence of microscopic colitis (MC) and associated factors related to MC in patients diagnosed with IBS. The study group (group I) consisted of 91 consecutive patients diagnosed with IBS based on the Rome III Criteria for whom colonoscopic examination was requested. The control group (group II) had 41 patients diagnosed with IBS considered as eligible for colonoscopic investigation due to specific conditions, and for whom colonoscopic examination was recommended for screening purposes due to a familial history of colon cancer. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. In the diarrhea-predominant IBS group, nine patients (9.89%) were diagnosed with microscopic colitis, seven with lymphocytic colitis (7.69%), and two with collagenous colitis (CC) (2.19%). None of the patients in group II were found to have MC (P = 0.007). There were no diagnoses of MC in the constipation-predominant and mixed type IBS groups. Clinicians should keep MC in mind for patients presenting with diarrhea-predominant IBS symptoms.

  14. Clostridium difficile associated infection, diarrhea and colitis

    PubMed Central

    Hookman, Perry; Barkin, Jamie S

    2009-01-01

    A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate

  15. Colitis and Colitis-Associated Cancer Are Exacerbated in Mice Deficient for Tumor Protein 53-Induced Nuclear Protein 1▿

    PubMed Central

    Gommeaux, Julien; Cano, Carla; Garcia, Stéphane; Gironella, Meritxell; Pietri, Sylvia; Culcasi, Marcel; Pébusque, Marie-Josèphe; Malissen, Bernard; Dusetti, Nelson; Iovanna, Juan; Carrier, Alice

    2007-01-01

    Tumor protein 53-induced nuclear protein 1 (TP53INP1) is an antiproliferative and proapoptotic protein involved in cell stress response. To address its physiological roles in colorectal cancer and colitis, we generated and tested the susceptibility of Trp53inp1-deficient mice to the development of colorectal tumors induced by injection of the carcinogen azoxymethane followed by dextran sulfate sodium (DSS)-induced chronic colitis. Trp53inp1-deficient mice showed an increased incidence and multiplicity of tumors compared to those of wild-type (WT) mice. Furthermore, acute colitis induced by DSS treatment was more severe in Trp53inp1-deficient mice than in WT mice. Treatment with the antioxidant N-acetylcysteine prevented colitis and colitis-associated tumorigenesis more efficiently in WT mice than in Trp53inp1-deficient mice, suggesting a higher oxidative load in the latter. Consistently, we demonstrated by electron spin resonance and spin trapping that colons derived from deficient mice produced more free radicals than those of the WT during colitis and that the basal blood level of the antioxidant ascorbate was decreased in Trp53inp1-deficient mice. Collectively, these results indicate that the oxidative load is higher in Trp53inp1-deficient mice than in WT mice, generating a more-severe DSS-induced colitis, which favors development of colorectal tumors in Trp53inp1-deficient mice. Therefore, TP53INP1 is a potential target for the prevention of colorectal cancer in patients with inflammatory bowel disease. PMID:17242209

  16. Surgical Management of Severe Colitis in the Intensive Care Unit.

    PubMed

    Halaweish, Ihab; Alam, Hasan B

    2015-12-01

    Severe colitis, an umbrella encompassing several entities, is one of the most common acute gastrointestinal disorders resulting in critical illness. Clostridium difficile infection is responsible for the majority of nosocomial diarrhea with fulminant C difficile colitis (CDC) carrying a high mortality. Optimal outcomes can be achieved by early identification and treatment of fulminant CDC, with appropriate surgical intervention when indicated. Ischemic colitis, on the other hand, is uncommon with a range of etiological factors including abdominal aortic surgery, inotropic drugs, rheumatoid diseases, or often no obvious triggering factor. Most cases resolve with nonsurgical management; however, prompt recognition of full-thickness necrosis and gangrene is crucial for good patient outcomes. Fulminant colitis is a severe disease secondary to progressive ulcerative colitis with systemic deterioration. Surgical intervention is indicated for hemorrhage, perforation, or peritonitis and failure of medical therapy to control the disease. Although, failure of medical management is the most common indication, it can be difficult to define objectively and requires a collaborative multidisciplinary approach. This article proposes some simple management algorithms for these clinical entities, with a focus on critically ill patients.

  17. Interleukin 19 reduces inflammation in chemically induced experimental colitis.

    PubMed

    Matsuo, Yukiko; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Nishiyama, Kazuhiro; Yoshida, Natsuho; Ikeda, Yoshihito; Fujimoto, Yasuyuki; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2015-12-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice. Inflammatory responses in IL-19-deficient mice were assessed using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of acute colitis. IL-19 deficiency aggravated TNBS-induced colitis and compromised intestinal recovery in mice. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of interferon-gamma, IL-12 (p40), IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5. Using this model of induced colitis, our results revealed the immunopathological relevance of IL-19 as an anti-inflammatory cytokine in intestinal inflammation in mice.

  18. Risk factors for complications after total colectomy in ulcerative colitis.

    PubMed

    Kim, In Kyoung; Park, Kyu Joo; Kang, Gyeong Hoon; Im, Jong Pil; Kim, Sang Gyun; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung

    2012-01-01

    Ulcerative colitis can be cured by total proctocolectomy. The aim of this study was to investigate the risk factors for colectomy-related complications in ulcerative colitis patients. All patients with ulcerative colitis who underwent total colectomy at Seoul National University Hospital from 1990 to 2009 were identified through a surgical database. Their demographic and clinical characteristics were reviewed retrospectively. They were followed for a mean of 6.2 years, and risk factors affecting the development of complications were analyzed. A total of 85 ulcerative colitis patients (M:F = 35:50) were enrolled and analyzed. Eighty (94.1%) patients received total proctocolectomy with ileal pouch-anal anastomosis. Thirty-nine (45.9%) patients had readmitted (95 hospitalizations) and 23 (27.1%) underwent further surgical procedures (44 operations) due to complications. Multivariate analysis showed that female gender (odds ratio [OR], 2.99; p=0.046), delayed surgery (OR, 3.45; p=0.03), and postoperative pathological diagnosis of dysplasia/cancer (OR, 4.22; p=0.03) were the risk factors for complication-related rehospitalization. Pouchitis (OR, 6.31; p=0.007) and frequent previous ulcerative colitis flare-up (OR, 1.39; p=0.023) were the risk factors for complication-related reoperation. Female gender, delayed surgery, pathological diagnosis of dysplasia/cancer, pouchitis, and frequent previous flare-up are the risk factors for postoperative complications.

  19. Recurrent Clostridium difficile colitis in cystic fibrosis: an emerging problem.

    PubMed

    Egressy, Katarine; Jansen, Michaelene; Meyer, Keith C

    2013-01-01

    To examine the incidence of recurrent Clostridium difficile infection in patients with cystic fibrosis (CF), including patients who had undergone lung transplantation, and review clinical findings in hospitalized patients with C. difficile colitis. A retrospective chart review was performed to examine the clinical presentation and management of patients with cystic fibrosis (CF) who received care at the University of Wisconsin Hospital and Clinics (UWHC) from 1994 to 2011 and were prospectively identified with C. difficile colitis. Ten cases of C. difficile associated disease (CDAD) occurred in patients with CF followed by our Adult CF Center over a period of 17 years, and 4 patients were bilateral lung transplant recipients. Two of the lung transplant recipients had recurrent CDAD that lead to fulminant pancolitis, surgical intervention, and shock. Two patients in the non-transplant group experienced recurrent C. difficile infection that led to fulminant pancolitis with associated systemic inflammatory response syndrome and required colectomy. C. difficile colitis can cause life threatening illness in patients with CF, and symptoms may be subtle and/or atypical and lead to significant delay in diagnosis. Patients with recurrent C. difficile colitis are at high risk of fatal outcome, and empiric therapy should be considered for patients with previous C. difficile colitis even in the absence of disease when broad-spectrum antibiotics are given to treat bacterial infection. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review

    PubMed Central

    Shirley, Debbie-Ann; Moonah, Shannon

    2016-01-01

    Background Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature to describe cases of fulminant amebic colitis associated with exposure to corticosteroid medications in order to identify the risk factors for poor outcome and determine difficulties in diagnosis and treatment. Methodology and Principal Findings Articles reporting severe and fulminant forms of amebic colitis between 1991 and 2016 were collected. 525 records were screened to identify 24 cases for qualitative analysis associated with corticosteroid use. Cases arose from areas of high endemicity or travel to such areas. Most cases (14 of 24, 58%) were given corticosteroids for initially misdiagnosed colitis, mainly inflammatory bowel, resulting in rapid progression of disease. Nearly half of all cases underwent surgical intervention, and 25% of cases died, despite all patients eventually receiving treatment with metronidazole. The odds of death did not differ significantly by prior misdiagnosis, co-morbidities, bowel perforation or need for surgery. Conclusions and Significance Infection with E. histolytica should be considered prior to the administration of corticosteroids, in particular for patients residing in endemic areas or those with appropriate travel history, especially prior to the diagnosis of inflammatory bowel disease. The development of preventative and treatment interventions are needed to improve outcomes of fulminant disease. PMID:27467600

  1. Endoscopic findings and lesion distribution in amebic colitis.

    PubMed

    Horiki, Noriyuki; Furukawa, Keiichi; Kitade, Takashi; Sakuno, Takashi; Katsurahara, Masaki; Harada, Tetsuro; Tano, Shunsuke; Yamada, Reiko; Hamada, Yasuhiko; Inoue, Hiroyuki; Tanaka, Kyosuke; Gabazza, Esteban C; Ishii, Naoki; Fukuda, Katsuyuki; Omata, Fumio; Fujita, Yoshiyuki; Tachibana, Hiroshi; Takei, Yoshiyuki

    2015-06-01

    A retrospective cohort study was conducted in 55 symptomatic patients with amebic colitis that visited at St. Luke's International Hospital and Mie University Hospital from 1994 through 2013. To diagnose amebic colitis, 40 patients underwent total colonoscopy within 1 week after hospital visiting and before receiving any treatment. The percentage of characteristic endoscopic findings of amebic colitis including discrete ulcers or erosions with white or yellow exudates were 0% in terminal ileum, 93% in cecum, 28% in ascending, 25% in transverse, 15% in descending, 20% in sigmoid colon and 45% in rectum. The rectal lesions in 55% of patients with amebic colitis were nonspecific. The trophozoite identification rate by direct smear of intestinal tract washings performed during colonoscopy was 88%. The protozoan identification rate was 70% in biopsy specimens taken from the periphery of the characteristic discrete ulcers. Total colonoscopy should be considered for the diagnosis of amebic colitis. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review.

    PubMed

    Shirley, Debbie-Ann; Moonah, Shannon

    2016-07-01

    Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature to describe cases of fulminant amebic colitis associated with exposure to corticosteroid medications in order to identify the risk factors for poor outcome and determine difficulties in diagnosis and treatment. Articles reporting severe and fulminant forms of amebic colitis between 1991 and 2016 were collected. 525 records were screened to identify 24 cases for qualitative analysis associated with corticosteroid use. Cases arose from areas of high endemicity or travel to such areas. Most cases (14 of 24, 58%) were given corticosteroids for initially misdiagnosed colitis, mainly inflammatory bowel, resulting in rapid progression of disease. Nearly half of all cases underwent surgical intervention, and 25% of cases died, despite all patients eventually receiving treatment with metronidazole. The odds of death did not differ significantly by prior misdiagnosis, co-morbidities, bowel perforation or need for surgery. Infection with E. histolytica should be considered prior to the administration of corticosteroids, in particular for patients residing in endemic areas or those with appropriate travel history, especially prior to the diagnosis of inflammatory bowel disease. The development of preventative and treatment interventions are needed to improve outcomes of fulminant disease.

  3. Ticlopidine induced colitis: a histopathological study including apoptosis.

    PubMed Central

    Berrebi, D; Sautet, A; Flejou, J F; Dauge, M C; Peuchmaur, M; Potet, F

    1998-01-01

    AIMS: To describe ticlopidine related microscopic colitis and to assess the occurrence of apoptosis in the colon epithelium. METHODS: A series of colorectal biopsy samples from nine patients with ticlopidine related chronic diarrhoea were analysed. Biopsies were also taken from five of these patients between two and four months after ticlopidine withdrawal. The number of apoptotic cells in the crypts/mm2 (apoptotic index) was calculated using in situ labelling by terminal deoxyribonucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling (TUNEL). All specimens were matched to normal colorectal specimens from a control group of comparable age and sex distribution. RESULTS: Histological examination of the colon biopsy specimens taken from all nine patients with ticlopidine related chronic diarrhoea showed characteristic features of microscopic colitis. The histology returned to normal when ticlopidine was withdrawn. Apoptotic cells were rarely found in controls, and the mean apoptotic index was 0.53. The apoptotic index was significantly higher (16.53) in ticlopidine related colitis, but decreased dramatically to control value when ticlopidine was withdrawn. CONCLUSION: Microscopic colitis can be induced by ticlopidine and is accompanied by an increase in epithelial apoptosis. Hence, increased apoptosis might be related to drug injury or might be part of microscopic colitis. Images PMID:9659239

  4. The effect of pentoxifylline and its metabolite-1 on inflammation and fibrosis in the TNBS model of colitis.

    PubMed

    Peterson, Theresa C; Peterson, Marc R; Raoul, Jennifer M

    2011-07-15

    TNBS-induced colitis has characteristics resembling human Crohn's disease including transmural inflammation, ulceration, and fibrosis. Current treatments target acute symptoms but do not necessarily prevent fibrotic complications of the disease. The aim of this study was to determine the effect of pentoxifylline and its primary metabolite (M-1) on fibrosis in the TNBS-induced colitis model. Myeloperoxidase activity and interleukin-18 are indicators of inflammation and were elevated in the TNBS model. The morphology damage score assesses colon damage and was also elevated in the TNBS model. Collagen as the indicator of fibrosis was quantified and visualized by the Sirius Red/Fast Green staining technique and collagen type I was assessed by Western analysis. Collagen was elevated in the TNBS-induced model. Pentoxifylline and M-1 treatment significantly attenuated colon damage and inflammation in TNBS-colitis (P<0.05). M-1 treatment significantly reduced the TNBS-induced increase in colon weight, colon thickness and total collagen content (P<0.05). Results suggest that pentoxifylline and M-1 inhibit intestinal fibrosis in this experimental model and may prove beneficial in the treatment of intestinal fibrosis associated with human Crohn's disease with the added benefit of inhibiting inflammation and ulceration. This is the first study to examine the effects of racemic M-1 in vivo and one of the few studies to examine the effect of drugs on both inflammation and fibrosis in an experimental model of colitis.

  5. Review article: problematic proctitis and distal colitis.

    PubMed

    Gionchetti, P; Rizzello, F; Morselli, C; Campieri, M

    2004-10-01

    About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure, and therefore may be effectively treated with topical treatment, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side-effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short-chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy.

  6. Proteomic Patterns of Colonic Mucosal Tissues Delineate Crohn’s Colitis and Ulcerative Colitis

    PubMed Central

    Seeley, Erin H.; Washington, Mary K.; Caprioli, Richard M.; M’Koma, Amosy E.

    2013-01-01

    Purpose Although Crohn’s colitis (CC) and ulcerative colitis (UC) share several clinical features, they have different causes, mechanisms of tissue damage, and treatment options. Therefore, the accurate diagnosis is of paramount importance in terms of medical care. The distinction between UC/CC is made on the basis of clinical, radiologic, endoscopic, and pathologic interpretations but cannot be differentiated in up to 15% of IBD patients. Correct management of this “indeterminate colitis” (IC) depends on the accuracy of future, and yet not known, destination diagnosis (CC/UC). Experimental design We have developed a proteomic methodology that has the potential to discriminate between UC/CC. The histologic layers of 62 confirmed UC/CC tissues were analyzed using MALDI-MS for proteomic profiling. Results A Support Vector Machine algorithm consisting of 25 peaks was able to differentiate spectra from CC and UC with 76.9% spectral accuracy when using a leave-20%-out cross validation. Application of the model to the entire data set resulted in accurate classification of 19/26 CC patients and 36/36 UC patients when using a 2/3 correct cutoff. A total 114 peaks were found to have Wilcoxin p-values of less than 0.05. Conclusion/Clinical relevance This information may provide new avenues for the development of novel personalized therapeutic targets. PMID:23382084

  7. Integrating Immunologic Signaling Networks: The JAK/STAT Pathway in Colitis and Colitis-Associated Cancer

    PubMed Central

    Zundler, Sebastian; Neurath, Markus F.

    2016-01-01

    Cytokines are believed to be crucial mediators of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC). Many of these cytokines trigger cellular effects and functions through signaling via janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules. In this way, JAK/STAT signaling controls important events like cell differentiation, secretion of cytokines or proliferation and apoptosis in IBD in both adaptive and innate immune cells. Moreover, JAK/STAT signaling, especially via the IL-6/STAT3 axis, is believed to be involved in the transition of inflammatory lesions to tumors leading to colitis-associated cancer (CAC). In this review, we will introduce the main cellular players and cytokines that contribute to pathogenesis of IBD by JAK/STAT signaling, and will highlight the integrative function that JAK/STATs exert in this context as well as their divergent role in different cells and processes. Moreover, we will explain current concepts of the implication of JAK/STAT signaling in CAC and finally discuss present and future therapies for IBD that interfere with JAK/STAT signaling. PMID:26938566

  8. Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish population.

    PubMed

    O'Toole, Aoibhlinn; Coss, Alan; Holleran, Grainne; Keegan, Denise; Doherty, Glen; Sheahan, Kieran; Mulcahy, Hugh; O'Donoghue, Diarmuid

    2014-07-01

    Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.

  9. NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis.

    PubMed

    Itani, Shigehiro; Watanabe, Toshio; Nadatani, Yuji; Sugimura, Naoki; Shimada, Sunao; Takeda, Shogo; Otani, Koji; Hosomi, Shuhei; Nagami, Yasuaki; Tanaka, Fumio; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2016-12-14

    The inflammasomes induce maturation of pro-interleukin-1β (IL-1β) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1β, while it reduced IL-18 expression. Either exogenous IL-1β or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1β. Compared to wild-type mice, NLRP3(-/-) mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1β and IL-18 production; this phenotype was rescued by exogenous IL-1β or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1β and IL-18 may play a protective role against UC through different mechanisms.

  10. NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis

    PubMed Central

    Itani, Shigehiro; Watanabe, Toshio; Nadatani, Yuji; Sugimura, Naoki; Shimada, Sunao; Takeda, Shogo; Otani, Koji; Hosomi, Shuhei; Nagami, Yasuaki; Tanaka, Fumio; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2016-01-01

    The inflammasomes induce maturation of pro-interleukin-1β (IL-1β) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1β, while it reduced IL-18 expression. Either exogenous IL-1β or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1β. Compared to wild-type mice, NLRP3−/− mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1β and IL-18 production; this phenotype was rescued by exogenous IL-1β or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1β and IL-18 may play a protective role against UC through different mechanisms. PMID:27966619

  11. [Cytomegalovirus in ulcerative colitis in "Hospital Nacional 2 de Mayo"].

    PubMed

    Arévalo Suarez, F; Cerrillo Sánchez, G; Sandoval Campos, J

    2007-01-01

    The association between cytomegalovirus and ulcerative colitis has been reported by many authors, but the exact pathogenesis of this relationship remains unclear. We reviewed all ulcerative colitis cases whose diagnosis were made in Hospital dos de Mayo, during period 2000-2005, these cases were evaluated for Cytomegalovirus using inmunohistochemistry, also we described histological features of our cases. CMV was identified in 22.2% of all cases, none of them had been treated with inmunosuppressants previously, histological activity was reported in all positive cases and 42.8% negative cases for CMV; Crypt architectural abnormality was the most often histological finding, and the frequency of ulcerative colitis was 1.5 per year. Our findings are similar to those reported by foreign authors and is consistent with theory which maintains inflammatory changes of UC would help CMV's activation without using inmunosuppressants.

  12. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis.

    PubMed

    Jang, Jong-Chan; Lee, Kang Min; Ko, Seong-Gyu

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.

  13. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis

    PubMed Central

    Jang, Jong-Chan; Lee, Kang Min

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis. PMID:27293323

  14. Managing acute severe ulcerative colitis in the hosptialised setting.

    PubMed

    McClements, David; Probert, Chris

    2015-10-01

    Ulcerative colitis affects approximately 146 000 people in the UK and is the most common form of inflammatory bowel disease. The majority of patients will have uncomplicated disease, but around 1 in 10 patients will develop acute severe colitis. Despite modern medical management, colectomy rates of 27% and mortality rates of 1% are still reported. Good supportive care and intravenous corticosteroids remain the mainstay of treatment, but up to one-third of patents will not respond. The Travis criteria allow early recognition of those patients failing to improve by day 3, allowing timely planning of medical rescue therapy or surgery. Rescue therapy with either infliximab or ciclosporin appears equally efficacious. Patients naive to thiopurines seem to have better colectomy-free survival rates following rescue therapy than those previously exposed. We review the published evidence behind the conventional management of acute severe ulcerative colitis.

  15. Seasonal variations in the onset of ulcerative colitis.

    PubMed Central

    Moum, B; Aadland, E; Ekbom, A; Vatn, M H

    1996-01-01

    Several retrospective studies have reported seasonal variations in the relapse of ulcerative colitis, and two studies have found seasonality in the onset of ulcerative colitis, with a peak from August to January. This study was designed to investigate possible seasonal variations of onset of ulcerative colitis (UC) and Crohn's disease (CD). Patients with symptoms of one year or less were recruited from a prospective study of the incidence of inflammatory bowel disease, and the onset of symptoms was recorded month by month for four consecutive years. A total of 420 patients with UC and 142 patients with CD were included. There was monthly seasonality (p = 0.028) in symptomatic onset in December and January for UC but not for CD. It was found that environmental agents with known seasonality can be of importance for the seasonal variations of disease onset in UC. PMID:8675089

  16. Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice.

    PubMed

    Wu, Cong; Xu, Zheng; Gai, Renhua; Huang, Kehe

    2016-07-01

    Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-γ and IL-17 in colon explant cultures as well as IFN-γ and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-γ, IL-17, IL-1β and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-γ and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-γ and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis.

  17. Pulverized konjac glucomannan ameliorates oxazolone-induced colitis in mice.

    PubMed

    Onitake, Toshiko; Ueno, Yoshitaka; Tanaka, Shinji; Sagami, Shintaro; Hayashi, Ryohei; Nagai, Kenta; Hide, Michihiro; Chayama, Kazuaki

    2015-09-01

    Pulverized konjac glucomannan (PKGM) is a natural biologically active compound extracted from konjac, a Japanese traditional food. In the present study, we investigated the role of PKGM in intestinal immunity in a mouse model of oxazolone (OXA)-induced colitis. C57BL/6(B6) mice were fed PKGM or control food from 2 weeks before the induction of OXA colitis. Body weight change, colon length, and histological change in the colon were examined. The mononuclear cells were purified from colon and stimulated with PMA/ionomycin. The levels of TNF-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 from the supernatant were measured by ELISA. Oral administration of PKGM prevented the body weight loss and shortening of colon length associated with OXA-induced colitis. Histological analysis revealed that the colonic inflammation was improved by the administration of PKGM. The levels of IL-4 and IL-13, the critical inflammatory cytokines in OXA colitis, derived from mononuclear cells from the lamina propria of the colon were significantly suppressed by PKGM administration. PKGM-fed mice showed a significantly lower IL-4/IFN-γ ratio in the colonic lamina propria compared with that in control-fed mice. Fluorescence-activated cell sorting analysis revealed that natural killer (NK) 1.1(+) T cells in the liver were significantly decreased in PKGM-fed mice. Finally, the preventive role of PKGM in OXA-induced colitis was not observed in invariant natural killer T cell-deficient mice. PKGM ameliorated OXA-induced colitis in mice. This effect is associated with a decreased population of NK1.1(+) T cells and induction of Th1-polarized immune responses.

  18. Recent advances in the management of radiation colitis

    PubMed Central

    Kountouras, Jannis; Zavos, Christos

    2008-01-01

    Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine. When dealing with radiation colitis and its complications, the most conservative modality should be employed because the areas of intestinal injury do not tend to heal. Acute radiation colitis is mostly self-limited, and usually, only supportive management is required. Chronic radiation colitis, a poorly predictable progressive disease, is considered as a precancerous lesion; radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease, including development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and cancer. Patients are commonly managed conservatively. Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery, and should be reserved for intestinal obstruction, perforation, fistulas, and severe bleeding. Owing to the difficulty in managing the complications of acute and chronic radiation colitis, particular attention should be focused onto the prevention strategies. Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches. A variety of novel, mostly experimental, agents have been used mainly as a prophylaxis, and improvements have been made in radiotherapy delivery, including techniques to reduce the amount of exposed intestine in the radiation field, as a critical strategy for prevention. PMID:19109862

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

    SciTech Connect

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

    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.

  20. Initial surgical management of ulcerative colitis in the biologic era.

    PubMed

    Geltzeiler, Cristina B; Lu, Kim C; Diggs, Brian S; Deveney, Karen E; Keyashian, Kian; Herzig, Daniel O; Tsikitis, Vassiliki L

    2014-12-01

    The initial minimum operation for ulcerative colitis is a total abdominal colectomy. Healthy patients may undergo proctectomy at the same time; however, for ill patients, proctectomy is delayed. Since the introduction of biologic medications in 2005, ulcerative colitis medical management has changed dramatically. We examined how operative management for ulcerative colitis has changed from the prebiologic to biologic eras. We conducted a retrospective review of data on patients with ulcerative colitis who were included in the Nationwide Inpatient Sample database. This study was conducted at a single university. A total of 1,547,852 patients with ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were included in the study. We examined patients whose initial operation consisted of total abdominal colectomy without proctectomy versus a total proctocolectomy with or without a pouch. We also examined which operation was done at the time of the construction of an ileoanal pouch. Patients who underwent colectomy and pouch construction in the same hospitalization were compared with those who received pouch formation at a subsequent hospitalization. Ulcerative colitis-related admissions rose by 170% during the years examined, and the number of patients who required total abdominal colectomy increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total proctocolectomy (p < 0.001). Pouch construction at a subsequent operation increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed total proctocolectomy as the most common initial surgical intervention for ulcerative colitis. The Nationwide Inpatient Sample is a retrospective database, and we were limited to examining the variables within it. Total abdominal colectomy is currently the most common initial operation for patients with ulcerative colitis, and an ileoanal pouch is more frequently constructed at a subsequent hospitalization. These trends coincide with

  1. Incidence and prevalence of ulcerative colitis in Punjab, North India

    PubMed Central

    Sood, A; Midha, V; Sood, N; Bhatia, A S; Avasthi, G

    2003-01-01

    Introduction: Ulcerative colitis occurs worldwide. It is considered common in most of Europe and North America and uncommon in most of the developing Asian countries. The incidence/prevalence of ulcerative colitis varies not only according to geographical region but also with race and ethnicity. There are no reported data from India on the incidence of the disease and its prevalence. Material and methods: A house to house survey was conducted by questionnaire, formulated to enquire about symptoms that are suggestive of ulcerative colitis. Those with prolonged diarrhoea with or without rectal bleeding were considered as suspected cases. These suspected cases were subjected to video sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already diagnosed and receiving treatment for ulcerative colitis, encountered during the survey, were reviewed. Resurvey of the same areas was conducted after a one year interval to detect new cases. Using direct methods, standardised rates were calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3, and 1 for each 10 year age group. Standardised rates were also obtained separately for males, females, and combined populations, using the Punjab state 1991 population census data. Rates were also estimated according to UK 2000 population data. Ninety five per cent confidence intervals (95% CI) of prevalence and incidence rates of ulcerative colitis were estimated under the assumption that the distribution of cases followed a Poisson probability model. Results: A total population of 51 910 were screened from January to March 1999. We identified 147 suspected cases and of these 23 were finally established as ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000 inhabitants (95% CI 29.4–66.6). A second visit to the same areas after one year identified 10 suspected cases in a population of 49 834. Of these, three were confirmed as “definite” ulcerative colitis giving a crude

  2. Protective effects of citicoline on TNBS-induced experimental colitis in rats.

    PubMed

    Ek, Rauf Onur; Serter, Mukadder; Ergin, Kemal; Cecen, Serpil; Unsal, Cengiz; Yildiz, Yuksel; Bilgin, Mehmet D

    2014-01-01

    The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.

  3. The mechanism of alopolysaccharide protecting ulceralive colitis.

    PubMed

    Lin, Hu; Honglang, Li; Weifeng, Li; Junmin, Chen; Jiantao, Yang; Junjing, Gu

    2017-04-01

    The aim of this study is to explain the mechanism of alopolysaccharide protecting ulceralive colitis in cells and animal models. We divided this study into two parts: cell and animal research parts. In the cell research, HT-29 cells were divided into normal group, model group, aloe polysacchride group and positive drug group, the cell model was used by tumor necrosis factor- α (TNF-α) combine with LPS, detecting IL-6 concentration of difference groups by Elisa testing, Apoptosis of each group was detected by flow cytometry. We detected JAK2 and STAT-3 gene expressions of difference groups by RT-PCR. WB assay was used to detect the expression of JAK2, p-JAK2, STAT-3 and p-STAT3 protein in the cells of each group. In animal experiment, SD rats were divided into normal group, model control group, aloe polysaccharide group and positive drug group. A rat model of colitis was established with 2,4,6- three nitrobenzene sulfonic acid (TNBS). IL-6 concentrations of difference groups were measured by Elisa test, and compared the colon length of difference groups, H&E staining observation of colon tissue changes in each group. We observed JAK2, p-JAK2, STAT-3 and p-STAT3 protein expression in colon tissues by immuno histochemistry and measured JAK2 and STAT-3 gene expression of difference groups by RT-PCR. We found IL-6 concentration and cell apoptosis rate of Model group were significantly up-regulation compared with normal group (P<0.05, respectively) in the cell experiment. Compared with Model group, The IL-6 concentration and apoptosis rate of aloe polysaccharide group and positive drug group were significantly down-regulation (P<0.05, respectively). In the gene expression, JAK2 and STAT-3 expression of aloe polysaccharide group and positive drug group were higher than model group (P<0.05, respectively). JAK2, p-JAK2, STAT-3 and p-STAT3 protein expression of Aloe polysaccharide group and positive drug group were lower than model group. In animal experiment, compared

  4. Managing osteoporosis in ulcerative colitis: Something new?

    PubMed Central

    Piodi, Luca Petruccio; Poloni, Alessandro; Ulivieri, Fabio Massimo

    2014-01-01

    The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX® tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that

  5. Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis.

    PubMed

    Winston, John H; Li, Qingjie; Sarna, Sushil K

    2013-08-15

    Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observed significant decline in ChAT, nNOS, and protein gene product (PGP) 9.5 protein and mRNA levels. In DSS colitis, ChAT and PGP9.5 were significantly upregulated while nNOS levels did not change. The nNOS dimer-to-monomer ratio decreased significantly in DSS- but not in TNBS-induced colitis. No differences were observed in the percentage of either ChAT (31 vs. 33%)- or nNOS (37 vs. 41%)-immunopositive neurons per ganglia or the mean number of neurons per ganglia (55 ± 5 vs. 59 ± 5, P > 0.05). Incubation of the distal colon muscularis externae in vitro with different types of inflammatory mediators showed that cytokines decreased ChAT and nNOS expression, whereas H₂O₂, a component of oxidative stress, increased their expression. NF-κB inhibitor MG-132 did not prevent the IL-1β-induced decline in either ChAT or nNOS expression. These findings showed that TNBS- and DSS-induced inflammation differentially regulates the expression of two critical proteins expressed in the colonic myenteric neurons. These differences are likely due to the exposure of the myenteric plexus neurons to different combinations of Th1-type inflammatory mediators and H₂O₂ in each model.

  6. Adherence in ulcerative colitis: an overview

    PubMed Central

    Testa, Anna; Castiglione, Fabiana; Nardone, Olga Maria; Colombo, Giorgio L

    2017-01-01

    Medication adherence is an important challenge while treating chronic illnesses, such as ulcerative colitis (UC), that require a long-term management to induce and maintain clinical remission. This review provides an overview of the role that medication adherence plays in the routine management of UC, with a focus on the results of a recent Italian study reporting the perception of patients with UC regarding adherence to treatment. A literature analysis was conducted on topics, such as measurement of adherence in real practice, causes, risk factors and consequences of non-adherence and strategies, to raise patients’ adherence. Most of the data refer to adherence to 5-aminosalicylic acid, and standard of care for the induction and maintenance of remission in UC. The adherence rate to 5-aminosalicylic acid is low in clinical practice, thus resulting in fivefold higher risk of relapse, likely increased risk of colorectal cancer, reduced quality of life and higher health care costs for in- and outpatient settings. There are various causes affecting non-adherence to therapy: forgetfulness, high cost of drugs, lack of understanding of the drug regimen – which are sometimes due to insufficient explanation by the specialist – anxiety created by possible adverse events, lack of confidence in physicians’ judgment and complex dosing regimen. The last aspect negatively influences adherence to medication both in clinical trial settings and in real-world practice. Regarding this feature, mesalamine in once-daily dosage may be preferable to medications with multiple doses per day because the simplification of treatment regimens improves adherence. PMID:28260866

  7. Surgical Indications and Procedures in Ulcerative Colitis.

    PubMed

    Cima, Robert R.; Pemberton, John H.

    2004-06-01

    Chronic ulcerative colitis (CUC) is an inflammatory bowel disease limited to the mucosa of the rectum and colon. The inflammation begins in the rectum and progresses uninterrupted for variable distances. To date, no etiologic factor has been identified. However, population studies suggest there is both a genetic and environmental component contributing to the development of CUC. The natural history is one of a chronic inflammatory state, characterized by intermittent flares of disease activity. In a small number of patients, the initial presentation of CUC is of a fulminant nature. Medical therapy for the intestinal manifestations of CUC is directed at controlling symptoms through treatment of the underlying inflammatory process. Medical therapy is not curative for either the intestinal or extraintestinal manifestation of CUC. However, surgical removal of the colon and rectum cures the intestinal manifestations of the disease and eliminates or markedly reduces the associated risk of malignancy in longstanding CUC. The indications for surgical intervention are divided into two broad categories that influence the type of surgery performed: emergent and elective surgery. Emergency operations are directed at life-threatening complications of CUC and are not intended as definitive surgical treatment for CUC. Alternatively, elective surgery is intended as definitive treatment for the intestinal component of the disease. In appropriately selected patients, the best surgical treatment option is the total proctocolectomy with an ileal pouch-anal anastomosis (IPAA). The IPAA avoids the need for a permanent stoma and maintains the normal route of defecation. This is a technically demanding operation and should be performed by surgeons comfortable with the procedure. The severity and frequency of complications related to IPAA have decreased significantly since the introduction of the operations in the early 1980s. More importantly, long-term follow-up of IPAA patients has

  8. A functional methylome map of ulcerative colitis

    PubMed Central

    Häsler, Robert; Feng, Zhe; Bäckdahl, Liselotte; Spehlmann, Martina E.; Franke, Andre; Teschendorff, Andrew; Rakyan, Vardhman K.; Down, Thomas A.; Wilson, Gareth A.; Feber, Andrew; Beck, Stephan; Schreiber, Stefan; Rosenstiel, Philip

    2012-01-01

    The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation. PMID:22826509

  9. A functional methylome map of ulcerative colitis.

    PubMed

    Häsler, Robert; Feng, Zhe; Bäckdahl, Liselotte; Spehlmann, Martina E; Franke, Andre; Teschendorff, Andrew; Rakyan, Vardhman K; Down, Thomas A; Wilson, Gareth A; Feber, Andrew; Beck, Stephan; Schreiber, Stefan; Rosenstiel, Philip

    2012-11-01

    The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation.

  10. Fecal microbiota in pouchitis and ulcerative colitis

    PubMed Central

    Li, Kai-Yu; Wang, Jian-Lin; Wei, Jiang-Peng; Gao, Sen-Yang; Zhang, Ying-Ying; Wang, Li-Tian; Liu, Gang

    2016-01-01

    AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis (UC) and pouchitis using genomic technology. METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis (IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16S rRNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16S rRNA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups (P < 0.001) and IPAA groups (P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC (r = -6.591, P < 0.01), was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis. CONCLUSION Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis. PMID:27833384

  11. Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study.

    PubMed

    Weng, Meng-Tzu; Tung, Chien-Chih; Lee, Yi-Shuan; Leong, Yew-Loong; Shieh, Ming-Jium; Shun, Chia-Tung; Wang, Cheng-Yi; Wong, Jau-Min; Wei, Shu-Chen

    2017-02-13

    Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.

  12. Prevalence of Microscopic Colitis in Patients with Chronic Diarrhea in Egypt: A Single-center Study

    PubMed Central

    Gado, Ahmed S.; Ebeid, Basel A.; El Hindawi, Ali A.; Akl, Maha M.; Axon, Anthony T.

    2011-01-01

    Background/Aim: Microscopic colitis (MC) is diagnosed when a patient with chronic watery non-bloody diarrhea (CWND) has an endoscopically normal colon, but colonic biopsies show unique inflammatory changes characteristic of lymphocytic or collagenous colitis. MC is a disorder of unknown etiology. Studies comparing the prevalence of the disease in developing countries as compared to developed countries may shed more light on the possibility of a post-infectious etiology. Most data on the incidence and prevalence of MC are from developed countries where it accounts for 4-13% of cases of CWND. There are only a few reports from developing countries. Two studies from Peru and Tunis, with high prevalence of infectious gastroenteritis, revealed MC in 40% and 29.3% of cases of CWND, respectively. The aim of this study was to investigate the prevalence of MC in patients presenting with CWND in Egypt. Materials and Methods: A total of 44 patients with CWND of unexplained etiology who had undergone full colonoscopy with no macroscopic abnormalities between January 2000 and January 2010 were assessed retrospectively. Results: The histological appearance of MC was identified in 22 (50%) patients. Twelve (55%) patients were male and 10 (45%) female. Mean age was 40 years (range: 20-65 years). Twenty (91%) of MC cases had lymphocytic colitis and 2 (9%) had collagenous colitis. Conclusions: The prevalence of MC in Egyptian patients with CWND is high when compared to that in developed countries. MC mainly affects young and middle-aged patients and it is more commonly of the lymphocytic type. PMID:22064335

  13. Clinical Characteristics of Microscopic Colitis in Korea: Prospective Multicenter Study by KASID

    PubMed Central

    Baek, Dae Hyun; Kim, Won Ho; Kim, Joo Sung; Yang, Suk-Kyun; Jung, Sung-Ae; Jang, Byung Ik; Choi, Chnag Hwan; Han, Dong Soo; Kim, Young-Ho; Chung, Yong Woo; Kim, Sang Woo; Kim, You Sun

    2011-01-01

    Background/Aims Microscopic colitis (MC) encompasses collagenous and lymphocytic colitis and is characterized by chronic diarrhea. In cases of MC, colonic mucosae are macroscopically normal, and diagnostic histopathological features are observed only upon microscopic examination. We designed a prospective multicenter study to determine the clinical features, pathological distribution in the colon and prevalence of MC in Korea. Methods We prospectively enrolled patients having watery diarrhea no more than 3 times a day between March 2008 and February 2009. We obtained patient histories and performed colonoscopies with random biopsies at each colon segment. Results A total of 100 patients with chronic diarrhea were enrolled for a normal colonoscopy and stool exam. MC was observed in 22 patients (22%) (M:F 1.2:1; mean age, 47.5 years). Of those 22 patients, 18 had lymphocytic colitis and 4 had collagenous colitis. The entire colon was affected in only 3 cases (13.6%), the ascending colon in 6 cases (27.2%), the transverse colon in 3 cases (13.6%), and the left colon in 3 cases (13.6%). More than 2 segments were affected in 7 cases (31.8%). Nonsteroidal anti-inflammatory drug-associated MCs were observed in 4 cases (18.2%), 3 of which showed improved diarrhea symptoms following discontinuation of the medication. Frequently associated symptoms were abdominal pain and weight loss. Autoimmune diseases were observed in 4 cases (18.2%). Half of the 22 patients with MC improved with conservative care by loperamide or probiotics. Conclusions In a prospective multicenter study of Korean patients with chronic diarrhea, the frequency of MC was found to be approximately 20%, similar to the percentage observed in Western countries. Therefore, the identification of MC is important for the adequate management of Korean patients with chronic diarrhea. PMID:21814598

  14. Differential immune and genetic responses in rat models of Crohn's colitis and ulcerative colitis

    PubMed Central

    Shi, Xuan-Zheng; Winston, John H.

    2011-01-01

    Crohn's disease and ulcerative colitis are clinically, immunologically, and morphologically distinct forms of inflammatory bowel disease (IBD). However, smooth muscle function is impaired similarly in both diseases, resulting in diarrhea. We tested the hypothesis that differential cellular, genetic, and immunological mechanisms mediate smooth muscle dysfunction in two animal models believed to represent the two diseases. We used the rat models of trinitrobenzene sulfonic acid (TNBS)- and dextran sodium sulfate (DSS)-induced colonic inflammations, which closely mimic the clinical and morphological features of Crohn's disease and ulcerative colitis, respectively. DSS inflammation induced oxidative stress initially in mucosa/submucosa, which then propagated to the muscularis externa to impair smooth muscle function. The muscularis externa showed no increase of cytokines/chemokines. On the other hand, TNBS inflammation almost simultaneously induced oxidative stress, recruited or activated immune cells, and generated cytokines/chemokines in both mucosa/submucosa and muscularis externa. The generation of cytokines/chemokines did not correlate with the recruitment and activation of immune cells. Consequently, the impairment of smooth muscle function in DSS inflammation was primarily due to oxidative stress, whereas that in TNBS inflammation was due to both oxidative stress and proinflammatory cytokines. The impairment of smooth muscle function in DSS inflammation was due to suppression of Gαq protein of the excitation-contraction coupling. In TNBS inflammation, it was due to suppression of the α1C1b subunit of Cav1.2b channels, CPI-17 and Gαq. TNBS inflammation increased IGF-1 and TGF-β time dependently in the muscularis externa. IGF-1 induced smooth muscle hyperplasia; both IGF-1 and TGF-β induced hypertrophy. In conclusion, both TNBS and DSS induce transmural inflammation, albeit with different types of inflammatory mediators. The recruitment or activation of

  15. Myo-inositol reduces β-catenin activation in colitis

    PubMed Central

    Bradford, Emily M; Thompson, Corey A; Goretsky, Tatiana; Yang, Guang-Yu; Rodriguez, Luz M; Li, Linheng; Barrett, Terrence A

    2017-01-01

    AIM To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-cateninS552 as a biomarker of recurrent dysplasia. METHODS We examined the effects of dietary myo-inositol treatment on inflammation, pβ-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, pβ-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pβ-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION Enumerating crypts with increased numbers of pβ-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials. PMID:28811707

  16. Diagnostic imaging advances in murine models of colitis.

    PubMed

    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-21

    Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

  17. Adolescents' Lived Experiences While Hospitalized After Surgery for Ulcerative Colitis

    PubMed Central

    Jensen, Susanne; Larsen, Lene; Sørensen, Erik Elgaard

    2016-01-01

    Adolescents are in a transitional phase of life characterized by major physical, emotional, and psychological challenges. Living with ulcerative colitis is experienced as a reduction of their life quality. Initial treatment of ulcerative colitis is medical, but surgery may be necessary when medical treatment ceases to have an effect. No research-based studies of adolescents' experience of the hospital period after surgery for ulcerative colitis exist. The objective of the study was to identify and describe adolescents' lived experiences while hospitalized after surgery for ulcerative colitis. This qualitative study was based on interviews with eight adolescents. Analysis and interpretation were based on a hermeneutic interpretation of meaning. Three themes were identified: Body: Out of order; Seen and understood; and Where are all the others? The adolescents experience a postoperative period characterized by physical and mental impairment. Being mentally unprepared for such challenges, they shun communication and interaction. The findings demonstrate the importance of individualized nursing care on the basis of the adolescent's age, maturity, and individual needs. Further study of adolescent patients' hospital stay, focusing on the implications of being young and ill at the same time, is needed. PMID:26425861

  18. Ulcerative Colitis and Crohn's Disease: Implications for College Health Programs

    ERIC Educational Resources Information Center

    Gelphi, A. P.

    1977-01-01

    The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)

  19. Tissue factor-dependent chemokine production aggravates experimental colitis.

    PubMed

    Queiroz, Karla C S; Van 't Veer, Cornelis; Van Den Berg, Yascha; Duitman, Janwillem; Versteeg, Henri H; Aberson, Hella L; Groot, Angelique P; Verstege, Marleen I; Roelofs, Joris J T H; Te Velde, Anje A; Spek, C Arnold

    2011-01-01

    Tissue factor (TF) is traditionally known as the initiator of blood coagulation, but TF also plays an important role in inflammatory processes. Considering the pivotal role of coagulation in inflammatory bowel disease, we assessed whether genetic ablation of TF limits experimental colitis. To this end, wild-type and TF-deficient (TFlow) mice were treated with 1.5% dextran sulfate sodium (DSS) for 7 d, and effects on disease severity, cytokine production and leukocyte recruitment were examined. Clinical and histological parameters showed that the severity of colitis was reduced in both heterozygous and homozygous TFlow mice compared with controls. Most notably, edema, granulocyte numbers at the site of inflammation and cytokine levels were reduced in TFlow mice. Although anticoagulant treatment with dalteparin of wild-type mice reduced local fibrin production and cytokine levels to a similar extent as in TFlow mice, it did not affect clinical and histological parameters of experimental colitis. Mechanistic studies revealed that TF expression did not influence the intrinsic capacity of granulocytes to migrate. Instead, TF enhanced granulocyte migration into the colon by inducing high levels of the granulocyte chemoattractant keratinocyte-derived chemokine (KC). Taken together, our data indicate that TF plays a detrimental role in experimental colitis by signal transduction-dependent KC production in colon epithelial cells, thereby provoking granulocyte influx with subsequent inflammation and organ damage.

  20. Association of lymphocytic colitis and lactase deficiency in pediatric population.

    PubMed

    Sun, Jihong; Lin, Jingmei; Parashette, Kalayan; Zhang, Jianjun; Fan, Rong

    2015-02-01

    Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. [Pseudomembranous colitis after surgery for a ruptured abdominal aortic aneurysm].

    PubMed

    Lozano Sánchez, F; Sánchez Fernández, J; Palacios, E; Fernández, M; Ingelmo Morin, A; Gómez Alonso, A

    1993-01-01

    We present a rare postoperative complication after surgical procedures for rupture of abdominal aortic aneurysms. The disease, a pseudomembranous colitis, was early recognized (by evidence of clostridium difficile after a coprocultive) and satisfactorily treated with vancomycin. From the literature review we found only a similar case but results were absolutely different from our case.

  2. CCR9 Antagonists in the Treatment of Ulcerative Colitis

    PubMed Central

    Bekker, Pirow; Ebsworth, Karen; Walters, Matthew J.; Berahovich, Robert D.; Ertl, Linda S.; Charvat, Trevor T.; Punna, Sreenivas; Powers, Jay P.; Campbell, James J.; Sullivan, Timothy J.; Jaen, Juan C.; Schall, Thomas J.

    2015-01-01

    While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation. PMID:26457007

  3. Ulcerative Colitis in Colonic Interposition for Esophageal Atresia

    PubMed Central

    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. PMID:27847835

  4. Ulcerative Colitis and Crohn's Disease: Implications for College Health Programs

    ERIC Educational Resources Information Center

    Gelphi, A. P.

    1977-01-01

    The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)

  5. Evaluation of dairy allergy among ulcerative colitis patients

    PubMed Central

    Judaki, Arezo; Hafeziahmadi, Mohamadreza; Yousefi, Atefe; Havasian, Mohamad Reza; Panahi, Jafar; Sayehmiri, Koroush; Alizadeh, Sajjad

    2014-01-01

    The intestine is the largest mucosal organ of the body and also the first line immune homeostasis. Inflammatory bowel disease or IBD is divided into ulcerative colitis and Crohn's disease. One of the problems that can occur with UC is dietary allergy to some foods. This study aimed to evaluated the dairy allergy among patients with ulcerative colitis. This study is a Case - control study, that studied 72 patients with Ulcerative Colitis, after recording history of the disease, colonoscopy and confirmed by biopsy and 72 person without history of colitis. In this study, in order to investigate of food allergy, used of the EUROMMUM kit with an international code number DP3420-1601-11E. We used chi-square and Monte Carlo method for analysis of data. Among UC patients, 30.6% mild, 52.8% moderate and 16.6% of cases were in sever stage. 9.7% of them reported a history of abdominal surgery due to disease. According to the chi-square and Monte Carlo methods, dairy allergy (including: cow milk, cow milk UHT and casein) in UC group was significant (P=0.00). This study indicated that there is significant relationship between UC and cow milk, cow milk UHT and casein. UC patients who are allergic to dairy products and the use of dairy products can increase the severity of UC. PMID:25512686

  6. Somatostatin regulates tight junction proteins expression in colitis mice.

    PubMed

    Li, Xiao; Wang, Qian; Xu, Hua; Tao, Liping; Lu, Jing; Cai, Lin; Wang, Chunhui

    2014-01-01

    Tight junction plays a critical role in intestinal defence. The alteration and perturbation of tight junction proteins could induce intestine barrier damage, and lead to the malabsorption of electrolytes and water. Previous studies had showed that colonic infection and inflammation could lead to the alteration of tight junction function, and somatostatin could protect intestinal epithelia. Thus, this study could explore that whether somatostatin could regulate tight junction in colitis mice. Colitis mice with diarrhea were induced by Citrobacter rodentium (CR) and Dextran sulfate sodium (DSS). In CR infected model, cladudin-1 and claudin-3 expression significantly decreased compared with the control mice (P<0.05); after octreotide treatment, claudin-1 and claudin-3 expression significantly increased compared with untreated CR infected mice (P<0.05). In DSS colitis model, occludin and claudin-3 expression significantly decreased compared with the control mice (P<0.05); and octreotide treatment could only significantly upregulate claudin-3 expression compared with untreated DSS colitis mice (P<0.05). To testify our results in vivo, we repeated the models in caco-2 cells by exposed with enteropathogenic Escherichia coli (E. Coli) and Tumor necrosis factor α (TNF-α). The results in vitro were consistent with in vivo study. The results suggested that somatostatin play a role in intestinal barrier protection by modulating tight junction proteins expression.

  7. Somatostatin regulates tight junction proteins expression in colitis mice

    PubMed Central

    Li, Xiao; Wang, Qian; Xu, Hua; Tao, Liping; Lu, Jing; Cai, Lin; Wang, Chunhui

    2014-01-01

    Tight junction plays a critical role in intestinal defence. The alteration and perturbation of tight junction proteins could induce intestine barrier damage, and lead to the malabsorption of electrolytes and water. Previous studies had showed that colonic infection and inflammation could lead to the alteration of tight junction function, and somatostatin could protect intestinal epithelia. Thus, this study could explore that whether somatostatin could regulate tight junction in colitis mice. Colitis mice with diarrhea were induced by Citrobacter rodentium (CR) and Dextran sulfate sodium (DSS). In CR infected model, cladudin-1 and claudin-3 expression significantly decreased compared with the control mice (P < 0.05); after octreotide treatment, claudin-1 and claudin-3 expression significantly increased compared with untreated CR infected mice (P < 0.05). In DSS colitis model, occludin and claudin-3 expression significantly decreased compared with the control mice (P < 0.05); and octreotide treatment could only significantly upregulate claudin-3 expression compared with untreated DSS colitis mice (P < 0.05). To testify our results in vivo, we repeated the models in caco-2 cells by exposed with enteropathogenic Escherichia coli (E. Coli) and Tumor necrosis factor α (TNF-α). The results in vitro were consistent with in vivo study. The results suggested that somatostatin play a role in intestinal barrier protection by modulating tight junction proteins expression. PMID:24966923

  8. Review-Ulcerative colitis and probiotics: An overview.

    PubMed

    Rather, Irfan Ahmad; Majumder, Rajib; Alshammari, Fanar Hamad; Park, Jae Gyu; Bajpai, Vivek Kumar

    2016-09-01

    Ulcerative colitis is an inflammatory disease of the large intestine whose effects are bloody diarrhea, cramping and bloating. The disease is usually relapsing and remitting. However, the cause of ulcerative colitis is not yet known. Due to this reason, finding an effective treatment has been a great challenge. The suggested medical treatment is usually composed of two portions; keeping the flare up from happening and treating the flare up when it has happened. Active flare ups are treated with corticosteroids. There are several hypothesis which suggest that ulcerative colitis could be due to the micro flora present in gut. For this reason, several researchers tried to modify the gut microflora with probiotics. However, there is no probiotics found that can induce emission faster than the placebo. The ulcerative colitis patients taking probiotics showed fewer and less severe symptoms during the flare up. This means that even though the probiotics did not end up the flare up faster, it slowed up the severity of the symptoms of the patients.

  9. Protein-tyrosine phosphatase sigma is associated with ulcerative colitis.

    PubMed

    Muise, Aleixo M; Walters, Thomas; Wine, Eytan; Griffiths, Anne M; Turner, Dan; Duerr, Richard H; Regueiro, Miguel D; Ngan, Bo-Yee; Xu, Wei; Sherman, Philip M; Silverberg, Mark S; Rotin, Daniela

    2007-07-17

    Inflammatory bowel disease (IBD), a relatively common chronic debilitating intestinal illness, is composed of two broadly defined groups, Crohn's disease (CD) and ulcerative colitis (UC). Although several susceptibility genes for CD have been recently described, susceptibility genes exclusive for UC have not been forthcoming. Here, we show that receptor protein-tyrosine phosphatase sigma (PTPRS-encoding PTPsigma) knockout mice spontaneously develop mild colitis that becomes severe when challenged with two known inducers of colitis. We also demonstrate that E-cadherin and beta-catenin, two important adherens junction proteins involved in maintenance of barrier defense in the colon, act as colonic substrates for PTPsigma. Furthermore, we show that three SNPs (rs886936, rs17130, and rs8100586) that flank exon 8 in the human PTPRS gene are associated with UC. The presence of these SNPs is associated with novel splicing that removes the third immunoglobulin-like domain (exon 9) from the extracellular portion of PTPsigma, possibly altering dimerization or ligand recognition. We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis.

  10. Non-specific colitis, is it a justifiable diagnosis?

    PubMed

    Haboubi, N Y; Kamal, F

    2001-07-01

    The terms non-specific and chronic colitis are often used by histopathologists. The aim of this study is to look into the validity of the label non-specific chronic colitis (NSCC), the consistency of its reporting, as well as its clinical usefulness in patients who, on review, have shown to have normal biopsies. Colonic and rectal biopsies from 35 patients who presented with acute onset diarrhoea, were initially diagnosed as nonspecific chronic colitis (NSCC) by a number of pathologists in one Department, and were reviewed by an outside pathologist (NYH) without the knowledge of the clinical details. A previously described set of histological criteria in reporting colonic biopsies in inflammatory conditions were used. Normal biopsies were found in 13 of the 35 patients (37%). These patients recovered without clinical intervention. In a further seven patients there was active inflammation with no features of chronicity, in 12 patients there were features of chronicity, in two patients there were hyperplastic polyps, and in one patient there were features of solitary ulcer syndrome. NSCC was used, without consistency, to cover a variety of conditions, including normal biopsies, sometimes relaying a wrong message. We suggest that histological criteria for chronicity should be adhered to when this label is used and the term Non-Specific Colitis should no longer be used.

  11. Agaricus bisporus attenuates dextran sulfate sodium-induced colitis.

    PubMed

    Um, Min Young; Park, Jae Ho; Gwon, So Young; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

    2014-12-01

    Agaricus bisporus (white button mushroom, WBM) is widely consumed in most countries and is reported to have anti-inflammatory and antioxidant activities. However, little is known regarding its effects in dextran sulfate sodium (DSS)-induced colitis, which are related to dysfunction of intestinal immunity. The aim of the present study was to investigate the effects of WBMs in an animal model of DSS-induced colitis. Male, 4-week-old ICR mice (n=10 per group) were fed a normal diet with or without 10% WBM for 4 weeks, and colitis was induced by 3% DSS in drinking water for 7 days. WBMs prevented DSS-induced shortening of colon length (P=.033) and diminished diarrhea (P=.049) and gross bleeding (P=.001), resulting in a decreased disease activity index. Results of histological analysis showed that WBMs suppressed mucosal damage. In addition, WBMs attenuated the DSS-induced increase in myeloperoxidase activity (P=.012) and upregulation of proinflammatory cytokine tumor necrosis factor-α (P=.020) in the colon segment. Taken together, these findings suggest a possible role for the WBM as an immunomodulator that can prevent and/or treat ulcerative colitis.

  12. Alloferon Alleviates Dextran Sulfate Sodium-induced Colitis

    PubMed Central

    Kim, Hyemin; Im, Jong Pil; Kim, Joo Sung; Lee, Wang Jae

    2015-01-01

    Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-α-induced degradation and phosphorylation of IκB in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis. PMID:26140045

  13. Alloferon Alleviates Dextran Sulfate Sodium-induced Colitis.

    PubMed

    Kim, Hyemin; Im, Jong Pil; Kim, Joo Sung; Kang, Jae Seung; Lee, Wang Jae

    2015-06-01

    Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-α-induced degradation and phosphorylation of IκB in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis.

  14. Ozone enema: a model of microscopic colitis in rats.

    PubMed

    Eliakim, R; Karmeli, F; Rachmilewitz, D; Cohen, P; Zimran, A

    2001-11-01

    Ozone is one of the most powerful oxidants available, with many applications in industry and medicine. Medically relevant features of ozone include bacterial and virucidal properties, disinfection, sterilization, circulatory stimulation, and disruption of malignant cells. Ozone therapy is administered in various ways, including intravenously, intramuscularly, and intrarectally. The latter modality is used for the treatment of colitis and hepatitis. Our aim was to examine the effect of ozone water enema on normal and inflamed rat colonic mucosa. Ozone water (20 microg/ml) was prepared via ozone generator and administered intrarectally (0.5 ml) daily. Rats were killed one, three, and seven days after rectal ozone water administration, and their colons resected, rinsed, and weighed (grams per 10 cm). Damage was assessed macro- and microscopically and tissue processed for myeloperoxidase and nitric oxide synthase activity. Rats receiving saline served as controls. In an additional experiment colitis was induced by intrarectal iodoacetamide. Ozone therapy caused no macroscopic damage. Ozone therapy induced microscopic colitis, which lasted for at least a week and was accompanied by increase in segmental weight, myeloperoxidase and nitric oxide activity, and prostaglandin E2 generation. Ozone therapy had no protective effect on inflamed mucosa. In conclusion, ozone water therapy had a deleterious effect on normal colonic mucosa, suggesting intrarectal administration be reevaluated. Ozone water enema may serve as a model of microscopic colitis.

  15. Symptomatic sensorineural hearing loss in patients with ulcerative colitis.

    PubMed

    Casella, G; Corbetta, D; Zolezzi, M; Di Bella, C; Villanacci, V; Salemme, M; Milanesi, U; Antonelli, E; Baldini, V; Bassotti, G

    2015-12-01

    Sensorineural hearing loss has been reported as an extraintestinal manifestation of inflammatory bowel disease, especially in adult patients with ulcerative colitis. However, to date only a few series have been reported in the literature, and none from Italy. The aim of the present investigation was to assess the prevalence of symptomatic sensorineural hearing loss in Italian patients with ulcerative colitis. We retrospectively assessed the charts of all patients with ulcerative colitis who underwent otolaryngologic investigation in a 10-year period. Complete charts of 57 patients were available for the observation period. Reasons for head and neck investigation were transient, mild hearing loss and sporadic vertigo. Clinical and instrumental head and neck examination was unremarkable in all but one woman who complained of mild hearing loss without vertigo or tinnitus, in whom sensorineural hearing loss was diagnosed. In our series, sensorineural hearing loss was found in less than 2 % of adult patients with ulcerative colitis evaluated in a department of otolaryngology. Systematic evaluation for this extraintestinal manifestation should not be carried out unless hearing loss is present.

  16. Familial cutaneous photosensitivity and colitis with lethal outcome.

    PubMed Central

    Labrune, P; Huguet, P; Alagille, D; Odievre, M

    1991-01-01

    Three sibs out of four, born to unrelated parents, developed early cutaneous photosensitivity and severe colitis. All of them died from untreatable diarrhoea. A fourth boy, whose father was different, did not have the same symptoms. The origin of this syndrome remains unclear and, in particular, no metabolic defect could be detected. PMID:2002480

  17. Cellulose supplementation early in life ameliorates colitis in adult mice

    USDA-ARS?s Scientific Manuscript database

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (Crohn disease and ulcerative colitis) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption dur...

  18. Critical roles of TIPE2 protein in murine experimental colitis

    PubMed Central

    Lou, Yunwei; Sun, Honghong; Morrissey, Samantha; Porturas, Thomas; Liu, Suxia; Hua, Xianxin; Chen, Youhai H.

    2014-01-01

    Both commensal bacteria and infiltrating inflammatory cells play essential roles in the pathogenesis of inflammatory bowel disease. The molecular mechanisms whereby these pathogenic factors are regulated during the disease are not fully understood. We report here that a member of the TNFAIP8 (tumor necrosis factor-α-induced protein 8) family called TIPE2 (TNFAIP8-like 2, or TNFAIP8L2) plays a crucial role in regulating commensal bacteria dissemination and inflammatory cell function in experimental colitis induced by dextran sodium sulfate (DSS). Following DSS treatment, TIPE2-deficient mice, or chimeric mice that are deficient in TIPE2 only in their hematopoietic cells, lost less body weight and survived longer than wild type controls. Consistent with this clinical observation, TIPE2-deficient mice exhibited significantly less severe colitis and colonic damage. This was associated with a marked reduction in the colonic expression of inflammatory cytokines such as TNF-α, IL-6, and IL-12. Importantly, the ameliorated DSS-induced colitis in TIPE2−/− mice was also associated with reduced local dissemination of commensal bacteria and a weaker systemic inflammatory response. Combined with our previous report that TIPE2 is a negative regulator of anti-bacterial immunity, these results indicate that TIPE2 promotes colitis by inhibiting mucosal immunity to commensal bacteria. PMID:24973456

  19. Central Retinal Vein Occlusion Associated with Ulcerative Colitis.

    PubMed

    Seo, Yuri; Kim, Min; Kim, Jin Hyoung; Park, Jae Jun; Lee, Sung Chul

    2016-12-01

    To report a case of central retinal vein occlusion without macular edema associated with ulcerative colitis and its novel treatment with intravitreal dexamethasone. A 40-year-old man with ulcerative colitis presented with sudden visual disturbances. An initial fundus examination showed subtle yellow-to-white patches within the inner retina of the right eye superotemporal to the fovea. There were intraretinal hemorrhages and cotton-wool spots within the superior vascular arcade and nasal to the optic disc. Despite initiation of systemic corticosteroids, 2 weeks later there was an increase in retinal hemorrhages, formation of cotton wool spots, and development of optic disc swelling in the right eye. The patient was eventually diagnosed with nonischemic central retinal vein occlusion associated with ulcerative colitis. He received sustained-release intravitreal dexamethasone, which led to the resolution of retinal hemorrhage, optic disc swelling, and cotton-wool spots. Three months after the injection, retinal hemorrhages were not detectable. However, ocular coherence imaging showed marked thinning of the inner retina at the locations that were previously hyper-reflective. Central retinal vein occlusion is an uncommon ophthalmologic manifestation associated with ulcerative colitis. Injection of intravitreal dexamethasone could be a viable treatment option in these patients even without the presence of macular edema.

  20. Clostridium difficile-associated diarrhea and colitis.

    PubMed

    Gerding, D N; Johnson, S; Peterson, L R; Mulligan, M E; Silva, J

    1995-08-01

    To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic

  1. Factors predicting poor prognosis in ischemic colitis

    PubMed Central

    Añón, Ramón; Boscá, Marta Maia; Sanchiz, Vicente; Tosca, Joan; Almela, Pedro; Amorós, Cirilo; Benages, Adolfo

    2006-01-01

    AIM: To determine the clinical, analytical and endoscopic factors related to ischemic colitis (IC) severity. METHODS: A total of 85 patients were enrolled in a retrospective study from January 1996 to May 2004. There were 53 females and 32 males (age 74.6 ± 9.4 years, range 45-89 years). The patients were diagnosed as IC. The following variables were analyzed including age, sex, period of time from the appearance of symptoms to admission, medical history, medication, stool frequency, clinical symptoms and signs, blood tests (hemogram and basic biochemical profile), and endoscopic findings. Patients were divided in mild IC group and severe IC group (surgery and/or death). Qualitative variables were analyzed using chi-square test and parametric data were analyzed using Student's t test (P < 0.05). RESULTS: The mild IC group was consisted of 69 patients (42 females and 27 males, average age 74.7 ± 12.4 years). The severe IC group was composed of 16 patients (11 females and 5 males, average age of 73.8 ± 12.4 years). One patient died because of failure of medical treatment (no surgery), 15 patients underwent surgery (6 after endoscopic diagnosis and 9 after peroperatory diagnosis). Eight of 85 patients (9.6%) died and the others were followed up as out-patients for 9.6 ± 3.5 mo. Demographic data, medical history, medication and stool frequency were similar in both groups (P > 0.05). Seriously ill patients had less hematochezia than slightly ill patients (37.5% vs 86.9%, P = 0.000). More tachycardia (45.4% vs 10.1%, P = 0.011) and a higher prevalence of peritonism signs (75% vs 5.7%, P = 0.000) were observed in the severe IC group while the presence and intensity of abdominal pain were similar between two groups. Two patients with severe IC had shock when admitted. Regarding analytical data, more seriously ill patients were found to have anemia and hyponatremia than the mildly ill patients (37.5% vs 10.1%, P = 0.014 and 46.6% vs 14.9%, P = 0.012, respectively

  2. Clostridium Difficile, Colitis, and Colonoscopy: Pediatric Perspective.

    PubMed

    McConnie, Randolph; Kastl, Arthur

    2017-08-01

    Review tests available for detection of Clostridium difficile (C. Diff) induced disease, including when such tests should be done in children and how they should be interpreted. Multiple tests are available for detecting disease due to C. diff. These include colonoscopy and stool analysis. Colonoscopy with biopsy is the most sensitive test for detecting the presence of colitis. The toxins produced by the C. diff. (toxin A, toxin B, and binary toxin) are the agents that cause injury and disease. Only toxin producing C. diff. Strains will cause disease. Binary toxin by itself is not thought to produce disease. Binary toxin causes disease in humans when present with toxin A and B producing bacteria, and has been implicated with fulminant life threatening disease. Stool analyses vary in sensitivity and specificity depending on the assay used. The presence of toxin producing strains of C diff. in the stool does not equate with disease. The presence of a toxin-producing bacteria or toxins (A or B) only equates with disease if diarrhea or a diseased colon (toxic megacolon, ileus, and sepsis) is present. Nucleic acid amplification testing (NAAT), when used in the stool from patients with diarrhea, appears to be the most efficient study to detect the gene that encodes for toxin A and B and thus to diagnose C. diff.-induced disease. Infants have a high carriage rate of C. diff. and are believed not to develop disease from it or its toxins. Infants should not be tested for C. difficile. The NAAT is most specific when done on patients with diarrhea with liquid stools. Testing for C. difficile should only be done on patients with diarrhea. One can assume that a patient who has no diarrhea and is not ill does not have C. diff.-induced disease. Treatment should be limited to patients with diarrhea who test positive for C. diff. toxin (A or B) or toxin-producing bacteria. Direct testing for binary toxin is not commercially available. Binary toxin is only thought to cause disease

  3. Quality of Methods Reporting in Animal Models of Colitis

    PubMed Central

    Bramhall, Michael; Flórez-Vargas, Oscar; Stevens, Robert; Brass, Andy

    2015-01-01

    Background: Current understanding of the onset of inflammatory bowel diseases relies heavily on data derived from animal models of colitis. However, the omission of information concerning the method used makes the interpretation of studies difficult or impossible. We assessed the current quality of methods reporting in 4 animal models of colitis that are used to inform clinical research into inflammatory bowel disease: dextran sulfate sodium, interleukin-10−/−, CD45RBhigh T cell transfer, and 2,4,6-trinitrobenzene sulfonic acid (TNBS). Methods: We performed a systematic review based on PRISMA guidelines, using a PubMed search (2000–2014) to obtain publications that used a microarray to describe gene expression in colitic tissue. Methods reporting quality was scored against a checklist of essential and desirable criteria. Results: Fifty-eight articles were identified and included in this review (29 dextran sulfate sodium, 15 interleukin-10−/−, 5 T cell transfer, and 16 TNBS; some articles use more than 1 colitis model). A mean of 81.7% (SD = ±7.038) of criteria were reported across all models. Only 1 of the 58 articles reported all essential criteria on our checklist. Animal age, gender, housing conditions, and mortality/morbidity were all poorly reported. Conclusions: Failure to include all essential criteria is a cause for concern; this failure can have large impact on the quality and replicability of published colitis experiments. We recommend adoption of our checklist as a requirement for publication to improve the quality, comparability, and standardization of colitis studies and will make interpretation and translation of data to human disease more reliable. PMID:25989337

  4. Spinal NMDA NR1 Subunit Expression Following Transient TNBS Colitis

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2009-01-01

    Background: N-methyl-D-aspartic acid (NMDA) receptors play an important role in the development of hypersensitivity to visceral and somatic stimuli following inflammation or tissue injury. Our objective was to investigate the role of NMDA NR1 receptors in the spinal cord (T10-L1; L4-S1) of a subset of rats that remain hypersensitive following histological resolution of TNBS-induced colitis compared to saline treated rats and rats that had recovered both behaviorally and histologically. We hypothesized that NMDA NR1 subunit expression mediates hypersensitivity following transient TNBS colitis. Methods: Male Sprague-Dawley rats (150g-250g) received 20mg/rat intracolonic trinitrobenzene sulfonic acid (TNBS) in 50% ethanol or saline. Animals underwent nociceptive visceral/somatic pain testing 16 weeks after resolution of TNBS colitis. Animals were sacrificed and their spinal cord (T10-L1; L4-S1) was retrieved and 2-dimensional polyacrylamide gel electrophoresis and immunohistocytochemistry techniques were used to investigate spinal-NMDA receptor expression. Results: NR1001 was the only NMDA NR1 receptor subunit that was expressed in recovered and control rats, whereas hypersensitive animals expressed NR1011 and NR1111 as well as NR1001 subunits. Immunohistochemistry analysis demonstrated increased expression of NMDA NR1-N1, C1, and C2-plus expression in lamina I & II of the spinal cord (T10-L1; L4-S1) in hypersensitive rats but not in recovered/control rats. Conclusions: Selective increases in the expression of the NMDA NR1 splice variants occur in hypersensitive rats following resolution of TNBS colitis. This suggests that the NMDA NR1 receptor play an important role in the development of neuronal plasticity and central sensitization. The recombination of NR1 splice variants may serve as a key functional protein that maintains hypersensitivity following resolution of TNBS colitis. PMID:19406112

  5. Light-emitting diodes at 940nm attenuate colitis-induced inflammatory process in mice.

    PubMed

    Belém, Mônica O; de Andrade, Giovana M M; Carlos, Thalita M; Guazelli, Carla F S; Fattori, Victor; Toginho Filho, Dari O; Dias, Ivan F L; Verri, Waldiceu A; Araújo, Eduardo J A

    2016-09-01

    Inflammatory bowel disease (IBD) presents intense inflammatory infiltrate, crypt abscesses, ulceration and even loss of function. Despite the clinical relevance of IBD, its current therapy remains poorly effective. Infrared wavelength phototherapy shows therapeutic potential on inflammation. Our goal was to evaluate whether light-emitting diodes (LED) at 940nm are capable of mitigating the colitis-induced inflammatory process in mice. Forty male Swiss mice were assigned into five groups: control; control treated with LED therapy; colitis without treatment; colitis treated with LED therapy; colitis treated with Prednisolone. Experimental colitis was induced by acetic acid 7.5% (pH2.5) rectal administration. LED therapy was performed with light characterized by wavelength of 940nm, 45nm bandwidth, intensity of 4.05J/cm(2), total power of 270mW and total dose of 64.8J for 4min in a single application. Colitis-induced intestinal transit delay was inhibited by LED therapy. Colitis caused an increase of colon dimensions (length, diameter, total area) and colon weight (edema), which were inhibited by LED therapy. LED therapy also decreased colitis-induced tissue gross lesion, myeloperoxidase activity, microscopic tissue damage score and the presence of inflammatory infiltrate in all intestinal layers. Furthermore, LED therapy inhibited colitis-induced IL-1β, TNF-α, and IL-6 production. We conclude LED therapy at 940nm inhibited experimental colitis-induced colon inflammation in mice, therefore, rendering it a promising therapeutic approach that deserves further investigation.

  6. Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis.

    PubMed

    Jaszewski, R; Tolia, V; Ehrinpreis, M N; Bodzin, J H; Peleman, R R; Korlipara, R; Weinstock, J V

    1990-06-01

    To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohn's colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohn's colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohn's than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohn's colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohn's Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohn's colitis.

  7. Misdiagnosed amoebic colitis leading to severe dysentery and necrotizing colitis--report of a case and review of the literature.

    PubMed

    Mogensen, Trine H; Christiansen, Jens J; Eivindson, Martin V; Larsen, Carsten S; Tøttrup, Anders

    2014-03-01

    We present a case of amoebic colitis, misdiagnosed as inflammatory bowel disease and treated with corticosteroids, leading to severe necrotizing enterocolitis. We review the literature on the epidemiology, pathogenesis, diagnosis, and treatment of amoebic dysentery, with special emphasis on the association between immunosuppressive treatment and the development of severe invasive amoebiasis.

  8. Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer

    PubMed Central

    Chellappa, Karthikeyani; Deol, Poonamjot; Evans, Jane R; Vuong, Linh M; Chen, Gang; Briançon, Nadege; Bolotin, Eugene; Lytle, Christian; Nair, Meera G; Sladek, Frances M

    2016-01-01

    HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters (P1 and P2) active in the colon is not clear. Here, we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2-HNF4α in the proliferative compartment. Exon swap mice that express only P1- or only P2-HNF4α have different colonic gene expression profiles, interacting proteins, cellular migration, ion transport and epithelial barrier function. The mice also exhibit altered susceptibilities to experimental colitis (DSS) and colitis-associated colon cancer (AOM+DSS). When P2-HNF4α-only mice (which have elevated levels of the cytokine resistin-like β, RELMβ, and are extremely sensitive to DSS) are crossed with Retnlb-/- mice, they are rescued from mortality. Furthermore, P2-HNF4α binds and preferentially activates the RELMβ promoter. In summary, HNF4α isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer. DOI: http://dx.doi.org/10.7554/eLife.10903.001 PMID:27166517

  9. The antioxidant effect of Echinacea angustifolia and Echinacea purpurea in rat colitis model induced by acetic acid.

    PubMed

    Dogan, Z; Ergul, B; Sarikaya, M; Filik, L; Gonultas, M Alparslan; Hucumenoglu, S; Can, M

    2014-01-01

    Ulcerative colitis is a chronic inflammatory condition of the colon, and reactive oxidative metabolites (ROMs) play an important role in its pathogenesis. Alternative therapies such as herbal remedies are increasingly being used in the treatment of ulcerative colitis for better clinical outcome of ulcerative colitis and less adverse effects. Echinacea has many features including antioxidant and wound-healing properties. Hence, the present study was undertaken to evaluate the protective effect of Echinacea spp. on experimental colitis model induced by acetic acid in Wistar albino rats. Acute colitis was induced by intrarectal administration of acetic acid. Rats were divided into four groups, namely control, Echinacea-administered, Echinacea-administered-colitis and colitis. Malondialdehyde and total antioxidant status were assayed in tissue samples. Histopathological evaluation was also performed. Macroscopic and microscopic scores were significantly higher in colitis group compared to control, Echinacea and Echinacea-colitis groups (p < 0.001). There was no significant differences in respect of macroscopic and microscopic scores between control, Echinacea and Echinacea-colitis groups (p > 0.3, p > 0.22). Malondialdehyde levels were elevated in colitis group compared to other groups (p < 0.001). Total antioxidant status was significantly higher in Echinacea group compared with other groups and also significantly higher in Echinacea-colitis group compared with colitis group (p < 0.001, p < 0.001, respectively). Echinacea may possibly have some therapeutic usefulness in the management of ulcerative colitis (Tab. 2, Fig. 4, Ref. 35).

  10. Towards a new paradigm of microscopic colitis: Incomplete and variant forms

    PubMed Central

    Guagnozzi, Danila; Landolfi, Stefania; Vicario, Maria

    2016-01-01

    Microscopic colitis (MC) is a chronic inflammatory bowel disease that has emerged in the last three decades as a leading cause of chronic watery diarrhoea. MC classically includes two main subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Other types of histopathological changes in the colonic mucosa have been described in patients with chronic diarrhoea, without fulfilling the conventional histopathological criteria for MC diagnosis. Whereas those unclassified alterations remained orphan for a long time, the use of the term incomplete MC (MCi) is nowadays universally accepted. However, it is still unresolved whether CC, LC and MCi should be considered as one clinical entity or if they represent three related conditions. In contrast to classical MC, the real epidemiological impact of MCi remains unknown, because only few epidemiological studies and case reports have been described. MCi presents clinical characteristics indistinguishable from complete MC with a good response to budesonide and cholestiramine. Although a number of medical treatments have been assayed in MC patients, currently, there is no causal treatment approach for MC and MCi, and only empirical strategies have been performed. Further studies are needed in order to identify their etiopathogenic mechanisms, and to better classify and treat MC. PMID:27784958

  11. Epidemiological risk factors in microscopic colitis: a prospective case-control study.

    PubMed

    Fernández-Bañares, Fernando; de Sousa, Monia R; Salas, Antonio; Beltrán, Belén; Piqueras, Marta; Iglesias, Eva; Gisbert, Javier P; Lobo, Beatriz; Puig-Diví, Valentí; García-Planella, Esther; Ordás, Ingrid; Andreu, Montserrat; Calvo, Marta; Montoro, Miguel; Esteve, Maria; Viver, Josep M

    2013-02-01

    The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC. In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

  12. Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis.

    PubMed

    Günaltay, Sezin; Nyhlin, Nils; Kumawat, Ashok Kumar; Tysk, Curt; Bohr, Johan; Hultgren, Olof; Hultgren Hörnquist, Elisabeth

    2014-09-14

    To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients. Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction. IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001). The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC.

  13. Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis

    PubMed Central

    Günaltay, Sezin; Nyhlin, Nils; Kumawat, Ashok Kumar; Tysk, Curt; Bohr, Johan; Hultgren, Olof; Hultgren Hörnquist, Elisabeth

    2014-01-01

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients. METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction. RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001). CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. PMID:25232259

  14. Chronic non-bloody diarrhoea: a prospective study in Malmö, Sweden, with focus on microscopic colitis

    PubMed Central

    2014-01-01

    Background Chronic non-bloody diarrhoea affects up to 5% of the population. Microscopic colitis is one of the most common causes, encompassing the subtypes collagenous colitis and lymphocytic colitis. The diagnosis of microscopic colitis is made by histological examination of colonic mucosal biopsy specimens. The aim of this investigation was to determine whether laboratory parameters or questions about disease history or concomitant disease could be helpful in discriminating patients with MC from those with a histologically normal colonic mucosa. Findings Patients admitted for colonoscopy because of chronic non-bloody diarrhoea (>2 loose stools for >3 weeks) at endoscopy units in Malmö during 2007 and 2009, were enrolled. A total number of 78 patients were included (60 women, 18 men, median age 59, IQR 45–69 years). Out of these 78, 15 patients (19%) had microscopic colitis (CC; n = 10, LC; n = 5). MC was especially prevalent in patients above the age of 50 (25%). No differences were found between those with normal histology and MC in laboratory analyses (inflammatory and liver parameters). Neither were differences shown in questions regarding symptoms, environmental factors or concomitant diseases except for an association with celiac disease (p = 0.019) and a trend maybe indicating an inverse association with appendectomy (p = 0.057). Conclusions Microscopic colitis is associated with female gender, celiac disease and consumption of NSAIDs. Trends were observed indicating that age above 50 years, acute onset and absence of appendectomy may be associated with MC. No associations were observed with other symptoms, calprotectin levels or liver parameters. PMID:24731750

  15. Angiogenesis blockade as a new therapeutic approach to experimental colitis

    PubMed Central

    Danese, Silvio; Sans, Miquel; Spencer, David M; Beck, Ivy; Doñate, Fernando; Plunkett, Marian L; de la Motte, Carol; Redline, Raymond; Shaw, David E; Levine, Alan D; Mazar, Andrew P; Fiocchi, Claudio

    2007-01-01

    Background Neoangiogenesis is a critical component of chronic inflammatory disorders. Inhibition of angiogenesis is an effective treatment in animal models of inflammation, but has not been tested in experimental colitis. Aim To investigate the effect of ATN‐161, an anti‐angiogenic compound, on the course of experimental murine colitis. Method Interleukin 10‐deficient (IL10−/−) mice and wild‐type mice were kept in ultra‐barrier facilities (UBF) or conventional housing, and used for experimental conditions. Dextran sodium sulphate (DSS)‐treated mice were used as a model of acute colitis. Mice were treated with ATN‐161 or its scrambled peptide ATN‐163. Mucosal neoangiogenesis and mean vascular density (MVD) were assessed by CD31 staining. A Disease Activity Index (DAI) was determined, and the severity of colitis was determined by a histological score. Colonic cytokine production was measured by ELISA, and lamina propria mononuclear cell proliferation by thymidine incorporation. Result MVD increased in parallel with disease progression in IL10−/− mice kept in conventional housing, but not in IL10−/− mice kept in UBF. Angiogenesis also occurred in DSS‐treated animals. IL10−/− mice with established disease treated with ATN‐161, but not with ATN‐163, showed a significant and progressive decrease in DAI. The histological colitis score was significantly lower in ATN‐161‐treated mice than in scrambled peptide‐treated mice. Inhibition of angiogenesis was confirmed by a significant decrease of MVD in ATN‐161‐treated mice than in ATN‐163‐treated mice. No therapeutic effects were observed in the DSS model of colitis. ATN‐161 showed no direct immunomodulatory activity in vitro. Conclusion Active angiogenesis occurs in the gut of IL10−/− and DSS‐treated colitic mice and parallels disease progression. ATN‐161 effectively decreases angiogenesis as well as clinical severity and histological inflammation in IL10

  16. Alterations in the immunohistochemical expression of Das-1 and CG-3 in colonic mucosal biopsy specimens helps distinguish ulcerative colitis from Crohn disease and from other forms of colitis.

    PubMed

    Yantiss, Rhonda K; Das, Kiron M; Farraye, Francis A; Odze, Robert D

    2008-06-01

    Distinction between ulcerative colitis (UC) and Crohn disease (CD) in mucosal biopsies is often difficult. Das-1 and CG-3 are monoclonal antibodies directed against an unknown colonic epithelial protein and human tropomyosin isoform-5, respectively, both show altered expression in patients with UC. In this study, we evaluated the utility of Das-1 and CG-3 in distinguishing UC from CD and from other types of colitis. One colonic biopsy specimen from each of 85 patients with confirmed UC (n=25), CD (n=15), lymphocytic (n=15), collagenous (n=15), and ischemic (n=15) colitis, and also 10 samples from normal controls, were stained for Das-1 and CG-3 using standard techniques. Reactivity for Das-1 and CG-3 was noted to be absent or present, and the location (ie, surface+/-crypt epithelium) and degree (weak or strong) of CG-3 staining was recorded. Loss of Das-1 staining occurred more frequently in UC (96%) compared with CD (20%), lymphocytic (20%), collagenous (13%), and ischemic colitis (0%) cases, as well as controls (10%, P<0.001 for all comparisons). CG-3 positivity in crypt epithelium was significantly more common in UC (52%) compared with the other groups (P< or =0.02 for all comparisons). The combination of strong crypt CG-3 staining and loss of Das-1 staining was noted in 44% of UC cases, but not in any other type of colitis (P=0.003 for all comparisons). We conclude that the patterns of Das-1 and CG-3 staining in colonic mucosal biopsies may be clinically useful in distinguishing UC from CD and from other colitidies.

  17. Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis.

    PubMed

    Jin, Younggeon; Pridgen, Tiffany A; Blikslager, Anthony T

    2015-12-01

    We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice. We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited. This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.

  18. Circulating auto-antibody against hepatoma-derived growth factor (HDGF) in patients with ulcerative colitis.

    PubMed

    Nahamura, Hideji; Yoshida, Kenya; Kishima, Yoshihiko; Enomoto, Hirayuki; Uyama, Hirokazu; Kuroda, Toshifumi; Okuda, Yorihide; Hirotani, Tomonori; Ito, Hiroaki; Kawase, Ichiro

    2004-01-01

    Various circulating auto-antibodies have been reported in patients with ulcerative colitis. Hepatoma-derived growth factor (HDGF) is a mitogen, localized dominantly in the nucleus of proliferating cells. In this study, we demonstrated the circulating anti-HDGF auto-antibody and investigated its clinical roles in patients with ulcerative colitis. Anti-HDGF IgG antibodies were measured by the enzyme-linked immunosorbent assay with recombinant HDGF in 20 healthy volunteers and 40 patients with ulcerative colitis. Circulating anti-HDGF antibody was detected in the serum of a patient with total colitis by Western blotting. Anti-HDGF auto-antibodies were detected at 65.6% in the serum of patients with total/left-sided colitis, compared with healthy subjects at 10%. During active stage, the circulating anti-HDGF auto-antibodies were detected at a higher frequency of 78.3% than those in remission stage at 37.5%. Furthermore, the titers during active colitis were higher than those during the remission stage. Anti-HDGF auto-antibodies were not detected in any patients with proctitis. These findings suggest that anti-HDGF auto-antibodies in the serum of patients with ulcerative colitis would help to classify the total/left-sided colitis from proctitis, and the serial measurement of the titer would also be a good marker for the active colitis.

  19. Iloprost reduces colitis induced oxidative stress: An experimental study in rats.

    PubMed

    Aytaç, Erman; Teksöz, Serkan; Saygılı, Seha; Tortum, Osman Baran; Yavuz, Nihat; Sözer, Volkan; Göksel, Süha; Uzun, Hafize; Seymen, Hakkı Oktay; Göksoy, Ertuğrul

    2013-01-01

    Reactive oxygen species have a known potent role in the pathogenesis of ulcerative colitis. Iloprost, a pharmaceutical, is a chemically stable derivative of a naturally- occurring human prostacyclin. Several studies have demonstrated protective effects of iloprost via its antioxidant and its anti-inflammatory activity. The aim of this study is to evaluate the effects of iloprost on oxidant/antioxidant status, as well as the large bowel histopathology in experimental colitis. Forty adult male Wistar-albino rats were randomly divided in to four equal weight-matched groups: sham group (n=10), iloprost administered sham group (n=10), colitis group (n=10), iloprost administered colitis group (n=10). Acetic acid (1 ml of 4% solution) was used to induce colonic inflammation in the rats. Colonic tissue and plasma malondialdehyde levels were significantly lower in the iloprost administered colitis group than the colitis group (p<0.01). Tissue glutathione levels of the iloprost administered colitis group were significantly higher than the colitis group (p<0.001). We have demonstrated in this study iloprost to be an antioxidant, as well as iloprost demonstrating protective activity against colitis induced oxidative stress.

  20. Ischemic Colitis Secondary to Ergotamine Use: A Case Study

    PubMed Central

    Rodman, Regina E.; Willson, Thomas D.; Connolly, Mark M.; Podbielski, Francis J.

    2011-01-01

    A 48-year-old woman with a history of chronic migraines, initially admitted for inpatient management of intractable migraine headaches, developed new onset abdominal pain, hypotension, and diarrhea on hospital day number ten. In our institution's headache unit, patients are treated by a multidisciplinary approach, including individualized drug therapy based on diagnosis and previous response to therapy. Given the patient's hypotension and clinical appearance, she was transferred to the intensive care unit and treated for septic shock and metabolic acidosis. A bedside colonscopy revealed diffuse ischemic colitis. Final pathology after colon resection showed widespread, transmural necrosis of the colonic wall. We review the pathophysiology of ergotamine use and its potential association with ischemic colitis. PMID:22347148

  1. Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories?

    PubMed Central

    Sands, B E

    2006-01-01

    Immunosuppressive drugs have become a mainstay of therapy for the inflammatory bowel diseases. Although robust evidence exists in support of the use of these drugs in Crohn's disease, a close evaluation of the available data in ulcerative colitis reveals a much weaker evidence base. In particular, randomised controlled trials of azathioprine, the most commonly used immunosuppressive agent, do not provide rich evidence of efficacy whereas observational cohorts suggest this agent is effective, particularly in patients with relapsing disease who require corticosteroids. Ciclosporin is also effective in the most refractory cases but its efficacy needs to be carefully weighed against the possibility of rare but life threatening complications. Although the evidence base in support of immunosuppressive drugs in ulcerative colitis is not as strong as in Crohn's disease, these agents clearly have a role in the treatment of this disease. PMID:16531519

  2. Non-invasive Imaging of Colitis using Multispectral Optoacoustic Tomography.

    PubMed

    Bhutiani, Neal; Grizzle, William E; Galandiuk, Susan; Otali, Denis; Dryden, Gerald W; Egilmez, Nejat K; McNally, Lacey R

    2016-12-01

    Currently, several non-invasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease (IBD). Here, we assess the applicability and utility of multispectral optoacoustic tomography (MSOT) in evaluating the presence and severity of colitis. Mice with bacterial colitis demonstrated a temporally associated increase in mesenteric and colonic vascularity with an increase in mean signal intensity of oxygenated hemoglobin (p=0.004) by MSOT two days after inoculation. These findings were significantly more prominent 7 days after inoculation, with increased mean signal intensity of oxygenated hemoglobin (p=0.0002) and the development of punctate vascular lesions on the colonic surface, which corresponded to changes observed on colonoscopy as well as histology. With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, non-invasive imaging tool in evaluation of patients with IBD.

  3. Simultaneous acute appendicitis and pseudomembranous colitis in a pediatric patient.

    PubMed

    Vidrine, Steven R; Cortina, Chandler; Black, Marissa; Vidrine, Steven B

    2012-01-01

    Acute appendicitis is a common cause for pediatric surgery, with an increasing incidence as this population ages. Pseudomembranous colitis (PMC) from Clostridum difficle is being seen more frequently in pediatric patients, especially after treatment with antibiotics and in those with Hirschsprung's disease. Only three prior cases of appendicitis associated with PMC have been described in the literature, and all of them occurred in adult patients. Here, we describe the first documented pediatric case: a 16-year-old female who developed acute appendicitis while concomitantly being treated for suspected pseudomembranous colitis. We concur with previous authors that there may be an association between these two pathologies; furthermore, this association may not always be clinically apparent and may be both under-diagnosed and under-reported.

  4. Ulcerative colitis associated with chronic granulomatous disease: case report

    PubMed Central

    Imanzade, Farid; Sayarri, Aliakbar; Tajik, Pantea

    2015-01-01

    Chronic Granulomatous Disease (CGD) is an inherited primary immunodeficiency disease which increases the body’s susceptibility to infections caused by certain bacteria and fungi. CGD is a rare disease, caused by four genes, one type is 1X linked and the other three are “autosomal recessive”. Although clinical presentation is variable, but characteristic features are recurrent pneumonia, lymphadenitis, hepatic or other abscesses. Gastrointestinal tract symptoms are common in x-linked recessive form of CGD. These include gastric and esophageal obstruction and inflammatory bowel disease. GI involvement including small and large intestines, the findings of luminal narrowing and the presence of granuloma can make it difficult to distinguish from Crohn’s disease. On the other hands according to the literature ulcerative colitis is rarely reported in patients with CGD. Our case presented with ulcerative colitis with CGD. PMID:26328046

  5. Vitiligo in a patient receiving infliximab for refractory ulcerative colitis.

    PubMed

    Ismail, Waleed A; Al-Enzy, Saleh A; Alsurayei, Saqer A; Ismail, Ali E

    2011-06-01

    Infliximab is a chimerical monoclonal antibody that inhibits pro-inflammatory activity of tumour-necrosis factor alpha (TNFα) and it is the primary biological agent used in the treatment of moderate-to-severe ulcerative colitis (UC). We report a case of vitiligo following infliximab administration in a patient with refractory UC. The case serves as a reminder of adverse cutaneous reactions induced by TNFα-antagonist therapy.

  6. Immunological studies in ulcerative colitis. IV. Origin of autoantibodies.

    PubMed

    Lagercrantz, R; Hammarström, S; Perlmann, P; Gustafsson, B E

    1968-12-01

    The incidence and height of antibody titers to colon, assayed by indirect hemagglutination with a heat stable colon extract from germ free rats, is significantly higher in sera from patients with ulcerative colitis than in those from healthy controls or from patients with amebic liver abscess or dysentery. While sera from ulcerative colitis patients and controls are indistinguishable in regard to incidence and height of antibody titers to Forsman antigen, Staphylococcus aureus S 209, Clostridium difficile, and several common strains of E. coli, they have elevated titers and increased incidence of antibodies to a heat stable antigen of E. coli O14. Patients with amebic dysentery have normal titers of such antibodies. Absorption of patients' sera with E. coli O14 antigen inhibits the colon directed hemagglutination reaction in approximately 30% of the cases tested. Likewise, the anti-E. coli O14 reaction can sometimes be inhibited with the colon extract. Other E. coli strains and other bacteria are inactive or have only weak inhibitory activity. Hemagglutination inhibition experiments show that germ free rat colon and E. coli O14 contain common structures, depicted by antibodies in the patients' sera. This pattern of reactivity closely resembles that seen in rats made autoimmune to colon by injection of newborn rabbit colon. E. coli O14 is known to carry a heterogenetic antigen present in lower concentration (or activity) in most Enterobacteriaceae. Hemagglutination inhibition experiments with rabbit antisera to E. coli O14 suggest that the antigen common for E. coli O14 and colon is related to this heterogenetic antigen. The findings imply that this antigen, which is constantly present in low concentrations in the human colon, may give rise to anticolon antibody formation in ulcerative colitis through breakage of tolerance. Since this antigen is present in healthy individuals as well, additional factors are required to explain the induction of anti

  7. TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.

    PubMed

    Lapointe, Tamia K; Basso, Lilian; Iftinca, Mircea C; Flynn, Robyn; Chapman, Kevin; Dietrich, Gilles; Vergnolle, Nathalie; Altier, Christophe

    2015-07-15

    Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation. Copyright © 2015 the American Physiological Society.

  8. Oral microbiome composition changes in mouse models of colitis.

    PubMed

    Rautava, Jaana; Pinnell, Lee J; Vong, Linda; Akseer, Nadia; Assa, Amit; Sherman, Philip M

    2015-03-01

    Oral mucosal pathologies are frequent in inflammatory bowel disease (IBD). Since host-microbiome interactions are implicated in the pathogenesis of IBD, in this study the potential for changes affecting the oral microbiome was evaluated using two complementary mouse models of colitis: either chemically (dextran sulfate sodium) or with Citrobacter rodentium infection. After sacrifice, the tongue, buccal mucosa, saliva, colon, and stool samples were collected for analyses. Denaturing gradient gel electrophoresis was performed to assess bacterial 16S rRNA gene profiles. Relative changes were determined using quantitative polymerase chain reaction analysis for the phyla Bacteroidetes, Firmicutes, Spirochetes, and Actinobacteria, classes Gammaproteobacteria and Betaproteobacteria, and the genera Bacillus and Lactobacillus. These groups represent over 99% of the oral microbiota of healthy C57BL/6 mice. Both models of colitis changed the oral microbiome, with the buccal microbiome being the most resistant to alterations in composition (maximum 1.8% change, vs tongue maximum 2.5% change, and saliva which demonstrated up to 7.2% total changes in microbiota composition). Changes in the oral microbiota were greater after dextran sulfate sodium challenge, compared with C. rodentium-induced colitis. Using cluster analysis, tongue and buccal mucosal microbiota composition changed ∼ 5%, saliva ∼ 35%, while stool changed ∼ 10%. These findings indicate that dysbiosis observed in murine models of colitis is associated with changes in the composition of bacteria present in the oral cavity and in saliva. Such changes in the oral microbiota could be relevant to the etiology and management of oral mucosal pathologies observed in IBD patients. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    PubMed Central

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  10. MANAGEMENT OF ACUTE SEVERE ULCERATIVE COLITIS: A CLINICAL UPDATE

    PubMed Central

    SOBRADO, Carlos Walter; SOBRADO, Lucas Faraco

    2016-01-01

    ABSTRACT Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency

  11. Repeated fecal microbiota transplantation in a child with ulcerative colitis.

    PubMed

    Shimizu, Hirotaka; Arai, Katsuhiro; Abe, Jun; Nakabayashi, Kazuhiko; Yoshioka, Takako; Hosoi, Kenji; Kuroda, Makoto

    2016-08-01

    We report the case of an 11-year-old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.

  12. Modulation in Natriuretic Peptides System in Experimental Colitis in Rats.

    PubMed

    Lee, Chang Ho; Ha, Gi Won; Kim, Jong Hun; Kim, Suhn Hee

    2016-04-01

    Renin-angiotensin system is involved in the pathophysiology of colonic inflammation. However, there are a few reports about modulation of natriuretic peptide system. This study investigates whether a local atrial natriuretic peptide (ANP) system exists in rat colon and whether ANP plays a role in the regulation of colonic motility in experimental colitis rat model. Experimental colitis was induced by an intake of 5 % dextran sulfate sodium (DSS) dissolved in tap water for 7 days. After rats were killed, plasma hormone concentrations and mRNAs for natriuretic peptide system were measured. Functional analysis of colonic motility in response to ANP was performed using taenia coli. DSS-treated colon showed an increased necrosis with massive infiltration of inflammatory cells. The colonic natriuretic peptide receptor-A mRNA level and particulate guanylyl cyclase activity in response to ANP from colonic tissue membranes were higher, and the mRNA levels of ANP and natriuretic peptide receptor-B were lower in DSS-treated rats than in control rats. ANP decreased the frequency of basal motility in a dose-dependent manner but did not change the amplitude. The inhibitory responses of frequency of basal motility to ANP and 8-bromo-cGMP were enhanced in DSS-treated rat colon. In conclusion, augmentation of inhibitory effect on basal motility by ANP in experimental colitis may be due an increased expression of colonic natriuretic peptide receptor-A mRNA. These data suggest that local natriuretic peptide system is partly involved in the pathophysiology of experimental colitis.

  13. Granulocyte macrophage colony stimulating factor ameliorates DSS induced experimental colitis

    PubMed Central

    Sainathan, Satheesh K.; Hanna, Eyad M.; Gong, Qingqing; Bishnupuri, Kumar S.; Luo, Qizhi; Colonna, Marco; White, Frances V.; Croze, Ed; Houchen, Courtney; Anant, Shrikant; Dieckgraefe, Brian K.

    2015-01-01

    Background Sargramostim, granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Clinical trials show that Sargramostim induces clinical response and remission in patients with active Crohn's disease. To study the mechanism, we examined the effects of GM-CSF in the dextran sulphate sodium (DSS) induced acute colitis model. We hypothesized that GM-CSF may work through effects on dendritic cells (DCs). Methods Acute colitis was induced in Balb/c mice by administration of DSS in drinking water. Mice were treated with daily GM-CSF or PBS. To probe the role of plasmacytoid DCs (pDCs) in the response to GM-CSF, we further examine the effects of monoclonal antibody 440c, which is specific for a sialic acid-binding immunoglobulin (Ig)-like lectin expressed on pDCs. Results GM-CSF ameliorates acute DSS-induced colitis; resulting in significantly improved clinical parameters and histology. Microarray analysis showed reduced expression of pro-inflammatory genes including TNFα and IL1β; results further confirmed by real-time RT-PCR and serum Bio-plex analysis. GM-CSF treatment significantly expands pDCs and type 1 IFN production. Administration of mAb 440c completely blocked the therapeutic effect of GM-CSF. GM-CSF is also effective in RAG1−/− mice, demonstrating activity independent effects on T and B cells. IFN-β administration mimics the therapeutic effect of GM-CSF in DSS-treated mice. GM-CSF increases systemic and mucosal type 1 IFN expression and exhibits synergy with pDC activators, such as microbial CpG DNA. Conclusions GM-CSF is effective in the treatment of DSS colitis in a mechanism involving the 440c+ plasmacytoid DC population. PMID:17932977

  14. Perioperative Considerations in Crohn Disease and Ulcerative Colitis

    PubMed Central

    Nickerson, T. Paul; Merchea, Amit

    2016-01-01

    The management of inflammatory bowel disease (IBD) is medically and surgically complex. Numerous patient- and disease-oriented factors must be considered in treating patients with IBD, including nutritional replenishment/support, effect of immunosuppressive medications, extent of resection, and use of proximal diversion. Perioperative planning and optimization of the patient is imperative to ensuring favorable outcomes and limiting morbidity. These perioperative considerations in Crohn disease and ulcerative colitis are reviewed here. PMID:27247531

  15. Risk factors for complications in patients with ulcerative colitis.

    PubMed

    Manser, Christine N; Borovicka, Jan; Seibold, Frank; Vavricka, Stephan R; Lakatos, Peter L; Fried, Michael; Rogler, Gerhard

    2016-04-01

    Patients with ulcerative colitis may develop extraintestinal manifestations like erythema nodosum or primary sclerosing cholangitis or extraintestinal complications like anaemia, malabsorption or they may have to undergo surgery. The aim of this study was to investigate potential risk factors for complications like anaemia, malabsorption or surgery in ulcerative colitis. Data on 179 patients with ulcerative colitis were retrieved from our cross-sectional and prospective Swiss Inflammatory Bowel Disease Cohort Study data base for a median observational time of 4.2 years. Data were compared between patients with (n = 140) or without (n = 39) complications. Gender, age at diagnosis, smoking status, disease extent, delay of diagnosis or therapy, mesalamine (5-ASA) systemic and topical therapy, as well as other medication were analysed as potential impact factors. In the multivariate regression analysis a delay of 5-ASA treatment by at least two months (odds ratio (OR) 6.21 (95% confidence interval (CI) 2.13-18.14), p = 0.001) as well as a delay with other medication with thiopurines (OR 6.48 (95% CI 2.01-20.91), p = 0.002) were associated with a higher risk for complications. This significant impact of a delay of 5-ASA therapy was demonstrated for extraintestinal manifestations (EIMs) as well as extraintestinal complications (EICs). Extensive disease as well as therapy with methotrexate showed a significantly increased risk for surgery (extensive disease: OR 2.62 (1.02-6.73), p = 0.05, methotrexate: OR 5.36 (1.64-17.58), p = 0.006). A delay of 5-ASA therapy of more than two months in the early stage of ulcerative colitis (UC) constitutes a risk for complications during disease course. Extensive disease is associated with a higher risk for surgery.

  16. Risk factors for complications in patients with ulcerative colitis

    PubMed Central

    Borovicka, Jan; Seibold, Frank; Vavricka, Stephan R; Lakatos, Peter L; Fried, Michael; Rogler, Gerhard

    2016-01-01

    Background Patients with ulcerative colitis may develop extraintestinal manifestations like erythema nodosum or primary sclerosing cholangitis or extraintestinal complications like anaemia, malabsorption or they may have to undergo surgery. Objective The aim of this study was to investigate potential risk factors for complications like anaemia, malabsorption or surgery in ulcerative colitis. Methods Data on 179 patients with ulcerative colitis were retrieved from our cross-sectional and prospective Swiss Inflammatory Bowel Disease Cohort Study data base for a median observational time of 4.2 years. Data were compared between patients with (n = 140) or without (n = 39) complications. Gender, age at diagnosis, smoking status, disease extent, delay of diagnosis or therapy, mesalamine (5-ASA) systemic and topical therapy, as well as other medication were analysed as potential impact factors. Results In the multivariate regression analysis a delay of 5-ASA treatment by at least two months (odds ratio (OR) 6.21 (95% confidence interval (CI) 2.13–18.14), p = 0.001) as well as a delay with other medication with thiopurines (OR 6.48 (95% CI 2.01–20.91), p = 0.002) were associated with a higher risk for complications. This significant impact of a delay of 5-ASA therapy was demonstrated for extraintestinal manifestations (EIMs) as well as extraintestinal complications (EICs). Extensive disease as well as therapy with methotrexate showed a significantly increased risk for surgery (extensive disease: OR 2.62 (1.02–6.73), p = 0.05, methotrexate: OR 5.36 (1.64–17.58), p = 0.006). Conclusions A delay of 5-ASA therapy of more than two months in the early stage of ulcerative colitis (UC) constitutes a risk for complications during disease course. Extensive disease is associated with a higher risk for surgery. PMID:27087958

  17. Toxic megacolon during pregnancy in ulcerative colitis: A case report

    PubMed Central

    Quddus, Ayyaz; Martin-Perez, Beatriz; Schoonyoung, Henry; Albert, Matthew; Atallah, Sam

    2015-01-01

    Introduction Ulcerative colitis is an idiopathic inflammatory bowel condition whose peak incidence coincides with fertility in female patients. In pregnancy, acute fulminant colitis is rare, and, when it becomes refractory to maximum medical therapy, emergency colectomy is mandated. Over the past quarter century, there have been few reports of this rare event in the literature. Presentation of case We report a 26 year old primigravida female who presented with toxic megacolon during the third trimester of pregnancy, unresponsive to medical therapy. She subsequently underwent an urgent low transverse caesarean section with a total colectomy. Both mother and child made a satisfactory recovery post operatively. Discussion Although the fetus is at higher risk than the mother in such a circumstance, morbidity and mortality rates are still noticeably high for both, and therefore, prompt diagnosis is key. Conclusion It is imperative that female patients planning to conceive with a known diagnosis of ulcerative colitis liaise with their obstetricians and gastroenterologists early to optimise medical treatment to prevent the development of a toxic megacolon and that conception is planned during a state of remission. Should surgical intervention become required, this can be performed with favourable outcomes for mother and child, as demonstrated in this report. PMID:25942749

  18. Eosinophilic colitis: epidemiology, clinical features, and current management

    PubMed Central

    Alfadda, Abdulrahman A.; Storr, Martin A.; Shaffer, Eldon A.

    2011-01-01

    Primary eosinophilic gastrointestinal disorders (EGIDs) represent a spectrum of inflammatory gastrointestinal disorders in which eosinophils infiltrate the gut in the absence of known causes for such tissue eosinophilia. EGIDs can be subgrouped as eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC). The least frequent manifestation of EGIDs is EC. EC is a heterogeneous entity with a bimodal age distribution, presenting with either an acute self-limited bloody diarrhea in otherwise healthy infants or as a more chronic relapsing colitis in young adults. The pathophysiology of primary EC appears related to altered hypersensitivity, principally as a food allergy in infants and T lymphocyte-mediated (i.e. non-IgE associated) in young adults. In adults, symptoms include diarrhea, abdominal pain, and weight loss. Endoscopic changes are generally modest, featuring edema and patchy granularity. Although standardized criteria are not yet established, the diagnosis of EC depends on histopathology that identifies an excess of eosinophils. Therapeutic approaches are based on case reports and small case series, as prospective randomized controlled trials are lacking. Eosinophilic colitis in infants is a rather benign, frequently food-related entity and dietary elimination of the aggressor often resolves the disorder within days. Adolescent or older patients require more aggressive medical management including: glucocorticoids, anti-histamines, leukotriene receptors antagonists as well as novel approaches employing biologics that target interleukin-5 (IL-5) and IgE. This review article summarizes the current knowledge of EC, its epidemiology, clinical manifestations, diagnosis, and treatment. PMID:21922029

  19. Protective Effect of Laminaria japonica with Probiotics on Murine Colitis

    PubMed Central

    Bu, Youngmin; Bae, Jinhyun; Bang, Yu-mi; Kim, Jinsung; Lee, Hyejung; Beom-Joon, Lee; Hyun, Yoo Hye

    2014-01-01

    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. PMID:24948848

  20. Protective effect of Laminaria japonica with probiotics on murine colitis.

    PubMed

    Ko, Seok-Jae; Bu, Youngmin; Bae, Jinhyun; Bang, Yu-mi; Kim, Jinsung; Lee, Hyejung; Beom-Joon, Lee; Hyun, Yoo Hye; Park, Jae-Woo

    2014-01-01

    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-1 β , 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-1 β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1 β , 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.

  1. Exacerbated experimental colitis in TNFAIP8-deficient mice.

    PubMed

    Sun, Honghong; Lou, Yunwei; Porturas, Thomas; Morrissey, Samantha; Luo, George; Qi, Ji; Ruan, Qingguo; Shi, Songlin; Chen, Youhai H

    2015-06-15

    The TNF-α-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and bacterial infection, and its expression is upregulated in a number of human cancers. However, its physiologic and pathologic functions are unclear. In this study, we describe the generation of TIPE-deficient mice and their increased sensitivity to colonic inflammation. TIPE-deficient mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities. Their major organs, including lymphoid organs and intestines, were macroscopically and microscopically normal. However, after drinking dextran sodium sulfate-containing water, TIPE-deficient mice developed more severe colitis than wild type mice did, as demonstrated by decreased survival rates, increased body weight loss, and enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production in the colon. Bone marrow chimeric experiments revealed that TIPE deficiency in nonhematopoietic cells was responsible for the exacerbated colitis in TIPE-deficient mice. Consistent with this result, TIPE-deficient intestinal epithelial cells had increased rate of cell death and decreased rate of proliferation as compared with wild type controls. These findings indicate that TIPE plays an important role in maintaining colon homeostasis and in protecting against colitis.

  2. Exacerbated Experimental Colitis In TNFAIP8-deficient Mice

    PubMed Central

    Sun, Honghong; Lou, Yunwei; Porturas, Thomas; Morrissey, Samantha; Luo, George; Qi, Ji; Ruan, Qingguo; Shi, Songlin; Chen, Youhai H.

    2015-01-01

    The TNF-α-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and bacterial infection, and its expression is upregulated in a number of human cancers. However, its physiological and pathological functions are unclear. We describe here the generation of TIPE-deficient mice and their increased sensitivity to colonic inflammation. TIPE-deficient mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities. Their major organs including lymphoid organs and intestines were macroscopically and microscopically normal. However, after drinking dextran sodium sulfate-containing water, TIPE-deficient mice developed more severe colitis than wild type mice, as demonstrated by decreased survival rates, increased body weight loss, and enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production in the colon. Bone marrow chimeric experiments revealed that TIPE deficiency in non-hematopoietic cells was responsible for the exacerbated colitis in TIPE-deficient mice. Consistent with this result, TIPE-deficient intestinal epithelial cells had increased rate of cell death and decreased rate of proliferation as compared to wild type controls. Taken together, these findings indicate that TIPE plays an important role in maintaining colon homeostasis and in protecting against colitis. PMID:25948814

  3. Effect of ulcerative colitis and smoking on rectal blood flow.

    PubMed Central

    Srivastava, E D; Russell, M A; Feyerabend, C; Rhodes, J

    1990-01-01

    Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history. PMID:2210447

  4. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2010-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2–28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14–28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity. PMID:17703363

  5. Circulating antibodies to cow's milk proteins in ulcerative colitis

    PubMed Central

    Jewell, D. P.; Truelove, S. C.

    1972-01-01

    Sera from patients with ulcerative colitis (51), Crohn's disease (30), hypolactasia (13), untreated adult coeliac disease (11), irritable colon syndrome (24), and sera from 38 healthy control subjects were tested for antibodies to the principal cow's milk proteins—casein, α-lactalbumin, and β-lactoglobulin. The red-cell-linked antigen-antiglobulin reaction was used to determine the titres of direct agglutinating antibodies and IgA and IgG incomplete antibodies. Apart from patients with coeliac disease, direct agglutinating antibodies were found infrequently and then in low titres. Approximately 50% of subjects had low titres of IgA and IgG antibodies. However, the titres found in sera from patients with ulcerative colitis did not differ from those found in the control subjects or in patients with Crohn's disease, hypolactasia, or irritable colon syndrome. Patients with untreated coeliac disease frequently had high antibody titres to the milk proteins. In all subjects tested, incomplete antibodies of IgA or IgG immunoglobulin class occurred with equal frequency. The frequent occurrence in adults of low titres of antibodies to the milk proteins may be due to continued absorption of minute amounts of protein. Absorption of allergens may be facilitated by mucosal damage, such as that of coeliac disease, with stimulation of antibody production. At the present time, however, there is little evidence to suggest that milk allergy is a factor in the aetiology of ulcerative colitis. PMID:5087069

  6. Well-differentiated adenocarcinoma associated with ulcerative colitis

    PubMed Central

    Yamamoto, Tomoko; Hiroi, Atsuko; Itagaki, Hiroko; Kato, Yoichiro; Iizuka, Bunei; Itabashi, Michio; Shibata, Noriyuki; Nagashima, Yoji

    2017-01-01

    Objectives: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. Methods and Results: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. Conclusions: These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed. PMID:28255443

  7. Attenuation of colitis injury in rats using Garcinia cambogia extract.

    PubMed

    dos Reis, Samara Bonesso; de Oliveira, Caroline Candida; Acedo, Simone Coghetto; Miranda, Daniel Duarte da Conceição; Ribeiro, Marcelo Lima; Pedrazzoli, José; Gambero, Alessandra

    2009-03-01

    Inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis are chronic enteropathies that probably result from a dysregulated mucosal immune response. These pathologies are characterized by oxidative and nitrosative stress, leukocyte infiltration and up-regulation of pro-inflammatory substances. Current IBD treatment presents limitations in both efficacy and safety that stimulated the search for new active compounds. Garcinia cambogia extract has attracted interest due to its pharmacological properties, including gastroprotective effects. In this study, the antiinflammatory activity of a garcinia extract was assessed in TNBS-induced colitis rats. The results obtained revealed that garcinia administration to colitic rats significantly improved the macroscopic damage and caused substantial reductions in increases in MPO activity, COX-2 and iNOS expression. In addition, garcinia extract treatment was able to reduce PGE(2) and IL-1beta colonic levels. These antiinflammatory actions could be related to a reduction in DNA damage in isolated colonocytes, observed with the comet assay. Finally, garcinia extract caused neither mortality nor toxicity signals after oral administration. As such, the antiinflammatory effects provided by the Garcinia cambogia extract result in an improvement of several parameters analysed in experimental colitis and could provide a source for the search for new antiinflammatory compounds useful in IBD treatment.

  8. A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.

    PubMed

    Goretsky, Tatiana; Bradford, Emily M; Ryu, Hyunji; Tahir, Maryam; Moyer, Mary Pat; Gao, Tianyan; Li, Linheng; Barrett, Terrence A

    2016-02-19

    Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85(ΔIEC)) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β-catenin signaling. Despite worse colitis, p85(ΔIEC) mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients.

  9. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis.

    PubMed

    Johansson, Malin E V; Gustafsson, Jenny K; Holmén-Larsson, Jessica; Jabbar, Karolina S; Xia, Lijun; Xu, Hua; Ghishan, Fayez K; Carvalho, Frederic A; Gewirtz, Andrew T; Sjövall, Henrik; Hansson, Gunnar C

    2014-02-01

    The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10(-/-) mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.

  10. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis

    PubMed Central

    Johansson, Malin E V; Gustafsson, Jenny K; Holmén-Larsson, Jessica; Jabbar, Karolina S; Xia, Lijun; Xu, Hua; Ghishan, Fayez K; Carvalho, Frederic A; Gewirtz, Andrew T; Sjövall, Henrik; Hansson, Gunnar C

    2014-01-01

    Objective The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? Methods and results The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10−/− mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. Conclusions Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology. PMID:23426893

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

    PubMed

    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.

  12. Low concentrations of human neutrophil peptide ameliorate experimental murine colitis.

    PubMed

    Maeda, Takuro; Sakiyama, Toshio; Kanmura, Shuji; Hashimoto, Shinichi; Ibusuki, Kazunari; Tanoue, Shiroh; Komaki, Yuga; Arima, Shiho; Nasu, Yuichiro; Sasaki, Fumisato; Taguchi, Hiroki; Numata, Masatsugu; Uto, Hirofumi; Tsubouchi, Hirohito; Ido, Akio

    2016-12-01

    Human neutrophil peptides (HNPs) not only have antimicrobial properties, but also exert multiple immunomodulatory effects depending on the concentration used. We have previously demonstrated that the intraperitoneal administration of high-dose HNP-1 (100 µg/day) aggravates murine dextran sulfate sodium (DSS)-induced colitis, suggesting a potential pro-inflammatory role for HNPs at high concentrations. However, the role of low physiological concentrations of HNPs in the intestinal tract remains largely unknown. The aim of this study was to examine the effects of low concentrations of HNPs on intestinal inflammation. We first examined the effects of the mild transgenic overexpression of HNP-1 in DSS-induced colitis. HNP-1 transgenic mice have plasma HNP-1 levels similar to the physiological concentrations in human plasma. Compared to wild-type mice treated with DSS, HNP-1 transgenic mice treated with DSS had significantly lower clinical and histological scores, and lower colonic mRNA levels of pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. We then injected low-dose HNP-1 (5 µg/day) or phosphate-buffered saline (PBS) intraperitoneally into C57BL/6N and BALB/c mice administered DSS. The HNP-1-treated mice exhibited significantly milder colitis with reduced expression levels of pro-inflammatory cytokines compared with the PBS-treated mice. Finally, we examined the in vitro effects of HNP-1 on the expression of cytokines associated with macrophage activation. Low physiological concentrations of HNP-1 did not significantly affect the expression levels of IL-1β, TNF-α, IL-6 or IL-10 in colonic lamina propria mononuclear cells activated with heat-killed Escherichia coli, suggesting that the anti-inflammatory effects of HNP-1 on murine colitis may not be exerted by direct action on intestinal macrophages. Collectively, our data demonstrated a biphasic dose-dependent effect of HNP-1 on DSS-induced colitis: an

  13. Preventive and Therapeutic Euphol Treatment Attenuates Experimental Colitis in Mice

    PubMed Central

    Bento, Allisson F.; Marcon, Rodrigo; Schmidt, Éder C.; Bouzon, Zenilda L.; Pianowski, Luiz F.; Calixto, João B.

    2011-01-01

    Background The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action. Methodology/Principal Findings Colitis was induced in mice either with dextran sulfate sodium (DSS) or with 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the effect of euphol (3, 10 and 30 mg/kg) on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR) and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI), histological/microscopic damage score and myeloperoxidase (MPO) activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB). In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin) and integrin (ICAM-1, VCAM-1 and LFA-1) expression in colonic tissue. Conclusions/Significance Together, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest this plant

  14. Hydrogen sulfide and colonic epithelial metabolism: implications for ulcerative colitis.

    PubMed

    Jørgensen, J; Mortensen, P B

    2001-08-01

    Hydrogen sulfide (HS-) impairs the oxidation of butyrate in colonocytes and is found in excess in feces of patients with ulcerative colitis. The possible pathogenic role of HS- in ulcerative colitis was further investigated. To investigate the metabolic effect of free and bound fecal HS-, isolated rat colonocytes were incubated in the presence of butyrate without and with the addition of (1) HS- in water, (2) sterile filtrates of fecal homogenates supplemented and incubated with HS- and known sources of fecal HS- production, and (3) HS- incubated with fecal agents known to bind HS-. Oxidation rates were obtained by quantifying the production of CO2. Total and free HS-, as well as the fecal ability to bind HS-, were determined in health and ulcerative colitis. Compared to the production of CO2 by colonocytes incubated with 2 mmol/liter of butyrate, the further addition of 1.25 and 2.5 mmol/liter of HS- in water reduced the production of CO2 by 57.6+/-10.0 and 98.9+/-1.4%, respectively. However, when adding fecal filtrate of homogenate supplemented with HS- corresponding to 1.25 and 2.5 mmol/liter of HS- in water, the reduction of CO2 production was only 30.7+/-12.0 and 53.2+/-14.0%, respectively. Neither the fecal level of total or free HS- nor the remarkable fecal ability to bind HS- differed in health or quiescent and active ulcerative colitis. Bound HS- had no or little effect on CO2 production. Addition of fecal filtrate of nonsupplemented homogenate to colonocytes significantly reduced the oxidation of butyrate to CO2 about 25%, which could not be ascribed to fecal HS-. In conclusion, fecal HS- has little effect on butyrate oxidation in colonocytes and does not seem to play a pathogenic role for UC by impairing colonic epithelial metabolism. Other fecal agents seem to be more potent metabolic inhibitors than fecal HS-. The role of colonic contents in the pathogenesis of ulcerative colitis remains circumstantial.

  15. Low concentrations of human neutrophil peptide ameliorate experimental murine colitis

    PubMed Central

    Maeda, Takuro; Sakiyama, Toshio; Kanmura, Shuji; Hashimoto, Shinichi; Ibusuki, Kazunari; Tanoue, Shiroh; Komaki, Yuga; Arima, Shiho; Nasu, Yuichiro; Sasaki, Fumisato; Taguchi, Hiroki; Numata, Masatsugu; Uto, Hirofumi; Tsubouchi, Hirohito; Ido, Akio

    2016-01-01

    Human neutrophil peptides (HNPs) not only have antimicrobial properties, but also exert multiple immunomodulatory effects depending on the concentration used. We have previously demonstrated that the intraperitoneal administration of high-dose HNP-1 (100 µg/day) aggravates murine dextran sulfate sodium (DSS)-induced colitis, suggesting a potential pro-inflammatory role for HNPs at high concentrations. However, the role of low physiological concentrations of HNPs in the intestinal tract remains largely unknown. The aim of this study was to examine the effects of low concentrations of HNPs on intestinal inflammation. We first examined the effects of the mild transgenic overexpression of HNP-1 in DSS-induced colitis. HNP-1 transgenic mice have plasma HNP-1 levels similar to the physiological concentrations in human plasma. Compared to wild-type mice treated with DSS, HNP-1 transgenic mice treated with DSS had significantly lower clinical and histological scores, and lower colonic mRNA levels of pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. We then injected low-dose HNP-1 (5 µg/day) or phosphate-buffered saline (PBS) intraperitoneally into C57BL/6N and BALB/c mice administered DSS. The HNP-1-treated mice exhibited significantly milder colitis with reduced expression levels of pro-inflammatory cytokines compared with the PBS-treated mice. Finally, we examined the in vitro effects of HNP-1 on the expression of cytokines associated with macrophage activation. Low physiological concentrations of HNP-1 did not significantly affect the expression levels of IL-1β, TNF-α, IL-6 or IL-10 in colonic lamina propria mononuclear cells activated with heat-killed Escherichia coli, suggesting that the anti-inflammatory effects of HNP-1 on murine colitis may not be exerted by direct action on intestinal macrophages. Collectively, our data demonstrated a biphasic dose-dependent effect of HNP-1 on DSS-induced colitis: an amelioration at

  16. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis.

    PubMed

    Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

    2015-08-01

    Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators. Published by the BMJ Publishing

  17. [Microscopic colitis--more common cause of diarrhea than believed. Biopsies are the only way to diagnosis, drug treatment is effective].

    PubMed

    Tysk, Curt; Bohr, Johan; Olesen, Martin; Eriksson, Sune; Järnerot, Gunnar

    Microscopic colitis, encompassing collagenous and lymphocytic colitis, is a fairly common cause of chronic watery diarrhoea, especially in elderly women. In recent epidemiological studies the annual incidence of each disorder was 4-6/100.000 inhabitants. The aetiology is unknown. The main clinical symptoms are watery diarrhoea, weight loss and abdominal pain. Laboratory analyses are nondiagnostic, and the diagnoses rely on histopathological examination of colonic mucosal biopsies. There is an association to autoimmune diseases such as thyroid disorders, diabetes mellitus, celiac disease and arthritis. Budesonide is the best-documented treatment of collagenous colitis. It is superior to placebo in short-term therapy, but the long-term efficacy is not well studied. The evidence for other therapeutic alternatives such as loperamide, cholestyramine, bismuth subsalicylate, or 5-aminosalicylates is weak. In unresponsive severe disease azathioprine or methotrexate may be tried. There are at present no controlled data on the treatment of lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality.

  18. Differential Acute Effects of Selenomethionine and Sodium Selenite on the Severity of Colitis

    PubMed Central

    Hiller, Franziska; Oldorff, Lisa; Besselt, Karolin; Kipp, Anna Patricia

    2015-01-01

    The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. PMID:25867950

  19. Diffuse perforated necrotising amoebic colitis with histoplasmosis in an immunocompetent individual presenting as an acute abdomen.

    PubMed

    Badyal, Rama Kumari; Gupta, Rajesh; Vaiphei, Kim

    2013-06-27

    Perforated necrotising amoebic colitis associated with intestinal histoplasmosis has rarely been reported in an immunocompetent individual. Radiology and preoperative features are non-specific and requires histopathological examination for a definitive diagnosis. Hence, this condition needs to be considered in the differential diagnosis of complicated infective colitis.

  20. Colorectal cancers in ulcerative colitis from a low-prevalence area for colon cancer.

    PubMed

    Desai, Devendra; Shah, Sudeep; Deshmukh, Abhijit; Abraham, Philip; Joshi, Anand; Gupta, Tarun; Deshpande, Ramesh; Khandagale, Varun; George, Siji

    2015-03-28

    To determine the incidence and risk factors for colorectal cancer (CRC) in patients with ulcerative colitis from a low prevalence region for CRC. Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men (57.7%)] with ulcerative colitis (median disease duration 6, range: 1-39 years) for analysis. Of these, 131 (30.5%) had left-sided colitis and 159 (37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of CRC. Twelve patients (2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease - 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained significant. CRC occurred in 2.8% of patients with ulcerative colitis in our population - an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our population. The risk increased with extent and duration of disease.

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

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    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. PMID:26798415

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

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    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.

  3. Outbreak of acute colitis on a horse farm associated with tetracycline-contaminated sweet feed.

    PubMed Central

    Keir, A A; Stämpfli, H R; Crawford, J

    1999-01-01

    Exposure of a group of horses to tetracycline-contaminated feed resulted in acute colitis and subsequent death in one horse and milder diarrhea in 3 others. The most severely affected animal demonstrated clinical and pathological findings typical of colitis X. The other herdmates responded well to administration of zinc bacitracin. PMID:10572668

  4. Diffuse perforated necrotising amoebic colitis with histoplasmosis in an immunocompetent individual presenting as an acute abdomen

    PubMed Central

    Badyal, Rama Kumari; Gupta, Rajesh; Vaiphei, Kim

    2013-01-01

    Perforated necrotising amoebic colitis associated with intestinal histoplasmosis has rarely been reported in an immunocompetent individual. Radiology and preoperative features are non-specific and requires histopathological examination for a definitive diagnosis. Hence, this condition needs to be considered in the differential diagnosis of complicated infective colitis. PMID:23814195

  5. Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis.

    PubMed

    Esteve, M; Mallolas, J; Klaassen, J; Abad-Lacruz, A; Gonzàlez-Huix, F; Cabré, E; Fernández-Bañares, F; Menacho, M; Condom, E; Martí-Ragué, J; Gassull, M A

    1998-04-01

    Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa.

  6. The effect of sodium valproate on acetic acid-induced colitis in rats.

    PubMed

    Najafi, Ali; Motaghi, Ehsan; Hosseini, Mohammad Javad; Ghasemi-Pirbaluti, Masoumeh

    2017-02-01

    Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.

  7. Boswellia serrata has beneficial anti-inflammatory and antioxidant properties in a model of experimental colitis.

    PubMed

    Hartmann, Renata Minuzzo; Fillmann, Henrique Sarubbi; Martins, Maria Isabel Morgan; Meurer, Luise; Marroni, Norma Possa

    2014-09-01

    Ulcerative colitis is an inflammatory disease that involves only the colon and rectum, being characterized by leukocyte infiltrate and superficial ulcers in the intestinal mucosa. To evaluate the anti-inflammatory and antioxidant effects of extract from the Boswellia serrata plant in an experimental rat model of acute ulcerative colitis induced by the administration of acetic acid (AA). An extract of B. serrata (34.2 mg/kg/day) was administered by oral gavage for 2 days before and after the induction of colitis with 4 mL of 4% AA. The anal sphincter pressure in the colitis group showed a significant decrease compared to that of the control groups (p < 0.001). The analysis of the values of lipid peroxidation (LPO) obtained by substances that react with thiobarbituric acid (TBARS) showed a significantly increased LPO in the colitis group compared to the control groups (p < 0.001). The nitric oxide levels and the expression of inducible nitric oxide synthase (iNOS) showed a significant increase in the colitis group compared to control groups (p < 0.01). Both pretreatment and treatment with B. serrata exhibited significantly reduced lipid peroxidation, nitric oxide and iNOS and showed improvements in tissue injury and anal sphincter pressure in animals with ulcerative colitis. The B. serrata extract has protective anti-inflammatory and antioxidant effects that inhibit inflammatory mediators in acute experimental colitis.

  8. Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results.

    PubMed

    Sandborn, W J

    1999-05-01

    Smoking is protective against developing ulcerative colitis. Nicotine may be the cause of this protective effect. Controlled trials have demonstrated efficacy of transdermal nicotine for active ulcerative colitis. Side effects observed with transdermal nicotine include contact dermatitis, nausea, and lightheadedness. Topical administration of nicotine to the colon reduces nicotine blood concentrations and side effects, and may be of clinical benefit.

  9. Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.

    PubMed

    Neufert, Clemens; Becker, Christoph; Türeci, Özlem; Waldner, Maximilian J; Backert, Ingo; Floh, Katharina; Atreya, Imke; Leppkes, Moritz; Jefremow, Andre; Vieth, Michael; Schneider-Stock, Regine; Klinger, Patricia; Greten, Florian R; Threadgill, David W; Sahin, Ugur; Neurath, Markus F

    2013-04-01

    Molecular mechanisms specific to colitis-associated cancers have been poorly characterized. Using comparative whole-genome expression profiling, we observed differential expression of epiregulin (EREG) in mouse models of colitis-associated, but not sporadic, colorectal cancer. Similarly, EREG expression was significantly upregulated in cohorts of patients with colitis-associated cancer. Furthermore, tumor-associated fibroblasts were identified as a major source of EREG in colitis-associated neoplasms. Functional studies showed that Ereg-deficient mice, although more prone to colitis, were strongly protected from colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted tumor growth rather than initiation. Additionally, we demonstrated that fibroblast-derived EREG requires ERK activation to induce proliferation of intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate the functional relevance of EREG-producing tumor-associated fibroblasts, we developed a novel system for adoptive transfer of these cells via mini-endoscopic local injection. It was found that transfer of EREG-producing, but not Ereg-deficient, fibroblasts from tumors significantly augmented growth of colitis-associated neoplasms in vivo. In conclusion, our data indicate that EREG and tumor-associated fibroblasts play a crucial role in controlling tumor growth in colitis-associated neoplasms.

  10. Tumor fibroblast–derived epiregulin promotes growth of colitis-associated neoplasms through ERK

    PubMed Central

    Neufert, Clemens; Becker, Christoph; Türeci, Özlem; Waldner, Maximilian J.; Backert, Ingo; Floh, Katharina; Atreya, Imke; Leppkes, Moritz; Jefremow, Andre; Vieth, Michael; Schneider-Stock, Regine; Klinger, Patricia; Greten, Florian R.; Threadgill, David W.; Sahin, Ugur; Neurath, Markus F.

    2013-01-01

    Molecular mechanisms specific to colitis-associated cancers have been poorly characterized. Using comparative whole-genome expression profiling, we observed differential expression of epiregulin (EREG) in mouse models of colitis-associated, but not sporadic, colorectal cancer. Similarly, EREG expression was significantly upregulated in cohorts of patients with colitis-associated cancer. Furthermore, tumor-associated fibroblasts were identified as a major source of EREG in colitis-associated neoplasms. Functional studies showed that Ereg-deficient mice, although more prone to colitis, were strongly protected from colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted tumor growth rather than initiation. Additionally, we demonstrated that fibroblast-derived EREG requires ERK activation to induce proliferation of intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate the functional relevance of EREG-producing tumor-associated fibroblasts, we developed a novel system for adoptive transfer of these cells via mini-endoscopic local injection. It was found that transfer of EREG-producing, but not Ereg-deficient, fibroblasts from tumors significantly augmented growth of colitis-associated neoplasms in vivo. In conclusion, our data indicate that EREG and tumor-associated fibroblasts play a crucial role in controlling tumor growth in colitis-associated neoplasms. PMID:23549083

  11. Amebic colitis can mimic tuberculosis and inflammatory bowel disease on endoscopy and biopsy.

    PubMed

    Pai, Sanjay A

    2009-04-01

    Biopsies of 11 patients with histopathologically diagnosed amebic colitis was evaluated; endoscopically, they were suspected to have tuberculosis or inflammatory bowel disease. Amebiasis was suggested in the differential diagnosis in only 3 cases. Three patients had purely rectal or sigmoid involvement, whereas the others had ileocecal, cecal, ascending, or transverse colon disease. The biopsies showed cryptitis and depletion of mucin but no crypt branching. Crypt abscesses were seen in one biopsy. Trophozoites of Entamoeba histolytica were seen in the exudate in all cases. The trophozoites were round to oval, approximately 25 to 40 microm in diameter and had a single, round nucleus and periodic acid-Schiff-positive cytoplasm. Phagocytosed erythrocytes were present in the trophozoites. Some features of ulcerative colitis and infectious colitis, such as cryptitis and crypt abscesses, are also seen in amebic colitis. Amebic colitis must be included in the differential diagnosis of all patients with suspected inflammatory bowel disease and tuberculosis.

  12. Effects of Malva sylvestris and Its Isolated Polysaccharide on Experimental Ulcerative Colitis in Rats.

    PubMed

    Hamedi, Azadeh; Rezaei, Hossein; Azarpira, Negar; Jafarpour, Mehrnaz; Ahmadi, Fatemeh

    2016-01-01

    Malva sylvestris is an edible plant that is consumed as a herbal supplement for its antiulcer and colon cleansing properties in traditional Persian medicine. This study was designed to evaluate its effects on ulcerative colitis, which is a chronic gastrointestinal inflammation. Colitis was induced by rectal instillation of acetic acid solution. Rats in different groups received aqueous, n-hexane, or ethanolic fractions of the plant before induction of colitis. Isolated polysaccharide of plant was also tested in 2 groups before and after induction of colitis. Macroscopic and microscopic evaluation of colitis showed that the aqueous fraction was very effective in preventing the inflammation and efficacy was lower for ethanolic and n-hexane fractions. Polysaccharide was effective in reducing signs of inflammation, especially as pretreatment. These beneficial effects provide evidences that this plant can be suggested for patients with this disease to improve their health condition or to reduce adverse effects of their medication.

  13. Modulation of inflammatory response via α2-adrenoceptor blockade in acute murine colitis

    PubMed Central

    Bai, A; Lu, N; Guo, Y; Chen, J; Liu, Z

    2009-01-01

    Inflammatory bowel disease (IBD) is characterized by heavy production of proinflammatory cytokines such as tumour necrosis factor (TNF)-α and interleukin (IL)-1β. Interactions of the autonomic nervous system with local immune cells play an important role in the development of IBD, and the balance of autonomic nerve function is broken in IBD patients with sympathetic overactivity. However, the function of catecholamines in the progress of colitis is unclear. In this study, we examined the role of catecholamines via α2-adrenoreceptor in acute murine colitis. The expression of tyrosine hydroxylase (TH) and dopamine b-hydroxylase (DBH), two rate-limiting enzymes in catecholamine synthesis, was detected by immunohistochemistry in murine colitis. Murine colitis was induced by dextran sodium sulphate or trinitrobenzene sulphonic acid (TNBS), and the mice were administered RX821002 or UK14304, α2-adrenoceptor antagonists or agonists. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, TNF-α and IL-1β production and histology. Lamina propria mononuclear cells (LPMCs) from mice with TNBS colitis were cultured in the absence or presence of RX821002 or UK14304, and stimulated further by lipopolysaccharide. TH and DBH are induced in LPMCs of inflamed colon, the evidence of catecholamine synthesis during the process of colitis. RX821002 down-regulates the production of proinflammatory cytokines from LPMCs, while UK14304 leads to exacerbation of colitis. Together, our data show a critical role of catecholamines via α2-adrenoreceptors in the progress of acute colitis, and suggest that use of the α2-adrenoceptor antagonist represents a novel therapeutic approach for the management of colitis. PMID:19250273

  14. Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice With Colitis.

    PubMed

    MacEachern, Sarah J; Patel, Bhavik A; Keenan, Catherine M; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C; Beck, Paul L; MacNaughton, Wallace K; Sharkey, Keith A

    2015-08-01

    Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in epithelial hyporesponsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulfonic acid- or dextran sodium sulfate-induced colitis and in Il10(-/-) mice. Electrically evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10(-/-) mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen, and blood of mice. Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared with mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulfonic acid-induced colitis and associated bacterial translocation. Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces

  15. Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice with Colitis

    PubMed Central

    MacEachern, Sarah J.; Patel, Bhavik A.; Keenan, Catherine M.; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C.; Beck, Paul L.; MacNaughton, Wallace K.; Sharkey, Keith A.

    2015-01-01

    Background & Aims Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in the epithelial hypo-responsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulphonic acid- or dextran sodium sulfate-induced colitis and in Il10−/− mice. Methods Electrically-evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10−/− mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen and blood of mice. Results Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared to mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulphonic acid -induced colitis and associated bacterial translocation. Conclusions Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these

  16. Vitamin D treatment attenuates 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis

    PubMed Central

    Liu, Tianjing; Shi, Yongyan; Du, Jie; Ge, Xin; Teng, Xu; Liu, Lu; Wang, Enbo; Zhao, Qun

    2016-01-01

    Crohn’s disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability. Interestingly, it has more of an effect on local structure preservation and inflammation inhibition in CD than in UC mice. Vitamin D blocked the increase of helper T-cell type 1 (Th1)- and helper T-cell type 17 (Th17)-related cytokines in TNBS-induced colitis. But the increase of helper T-cell type 2 (Th2)- and regulatory T cells (Treg)-related cytokines was augmented at the same time in oxazolone-induced colitis which counteracted each other. Our study helps elucidate the differential protective effects of vitamin D on CD and UC patients, as reported in literature. PMID:27620138

  17. Intraperitoneal but Not Intravenous Cryopreserved Mesenchymal Stromal Cells Home to the Inflamed Colon and Ameliorate Experimental Colitis

    PubMed Central

    Castelo-Branco, Morgana T. L.; Soares, Igor D. P.; Lopes, Daiana V.; Buongusto, Fernanda; Martinusso, Cesonia A.; do Rosario, Alyson; Souza, Sergio A. L.; Gutfilen, Bianca; Fonseca, Lea Mirian B.; Elia, Celeste; Madi, Kalil; Schanaider, Alberto; Rossi, Maria Isabel D.; Souza, Heitor S. P.

    2012-01-01

    Background and Aims Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)–induced colitis. Methods After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. Results Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. Conclusions Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis. PMID:22432015

  18. [Medical therapy of inflammatory bowel diseases: ulcerative colitis].

    PubMed

    Lakatos, László; Lakatos, Péter László

    2007-06-24

    There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to

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

    PubMed

    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

  20. Dimethyl Fumarate Reduces Inflammatory Responses in Experimental Colitis

    PubMed Central

    Casili, Giovanna; Cordaro, Marika; Impellizzeri, Daniela; Bruschetta, Giuseppe; Paterniti, Irene; Cuzzocrea, Salvatore

    2016-01-01

    Background and Aims: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. Methods: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks’ treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8–10 weeks of age. The mechanism of this pharmacological potential of DMF [10 μM] was investigated in colonic epithelial cell monolayers [Caco-2] exposed to H2O2. The barrier function was evaluated by the tight junction proteins. Results: The treatment with DMF significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. DMF [30 and 100mg/kg] also caused a substantial reduction in the degree of colon injury, in the rise in myeloperoxidase [MPO] activity, and in the increase in tumour necrosis factor [TNF]-α expression, as well as in the up-regulation of ICAM-1 caused by DNBS in the colon. Molecular studies demonstrated that DMF impaired NF-κB signalling via reduced p65 nuclear translocalisation. DMF induced a stronger antioxidant response as evidenced by a higher expression of Mn-superoxide dismutase. Moreover, DMF protected human intestinal epithelial cells against H2O2-induced barrier dysfunction, restoring ZO-1 occludin expression, via the HO-1 pathway. Conclusions: DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease. PMID:26690241

  1. Protective pathways against colitis mediated by appendicitis and appendectomy

    PubMed Central

    Cheluvappa, R; Luo, A S; Palmer, C; Grimm, M C

    2011-01-01

    Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription–polymerase chain reaction (RT–PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group samples (false discovery rates < 1%; P-value < 0·001). Time–course RT–PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD. PMID:21707591

  2. Andrographis paniculata Extract (HMPL-004) for Active Ulcerative Colitis

    PubMed Central

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

    2013-01-01

    OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PMID:23044768

  3. Crohn’s and colitis in children and adolescents

    PubMed Central

    Day, Andrew S; Ledder, Oren; Leach, Steven T; Lemberg, Daniel A

    2012-01-01

    Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications. PMID:23139601

  4. Sarcoidosis associated with infliximab therapy in ulcerative colitis

    PubMed Central

    Gîlcă, Georgiana-Emmanuela; Diaconescu, Smaranda; Bălan, Gheorghe Gh.; Timofte, Oana; Ştefănescu, Gabriela

    2017-01-01

    Abstract Rationale: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs. Patient concerns: We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough. Diagnoses: Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis. Interventions: Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated. Patient outcomes: After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis. Lessons: Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon

  5. The effect of melatonin on TNBS-induced colitis.

    PubMed

    Necefli, Ahmet; Tulumoğlu, Burcu; Giriş, Murat; Barbaros, Umut; Gündüz, Mücteba; Olgaç, Vakur; Güloğlu, Recep; Toker, Gülçin

    2006-09-01

    Ulcerative colitis is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. The present study was undertaken to investigate the effect of melatonin administration on oxidative damage and apoptosis in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats were divided into four groups as follows: Group 1 (n=8)-T-NBS colitis; Group 2 (n=8)--melatonin, 10 mg/kg/day ip, for 15 days in addition to TNBS; Group 3 (n=8)--melatonin alone, 10 mg/kg/day ip, for 15 days; and Group 4 (n=8)-isotonic saline solution, 1 ml/rat ip, for 15 days (sham control group). Colonic myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels, and glutathione (GSH) levels are indicators of oxidative damage, while caspase-3 activities reveal the degree of apoptosis of the colonic tissue. In all TNBS-treated rats, colonic MPO activity and MDA levels were found to be increased significantly compared to those in the sham group. Colonic MPO activity and MDA levels were significantly lower in the melatonin treatment group compared to TNBS-treated rats. GSH levels of colonic tissues were found to be significantly lower in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly increased GSH levels compared to those in TNBS-treated rats. Caspas-3 activity of colonic tissues was found to be significantly higher in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly decreased caspase-3 activity compared to that in TNBS-treated rats. These results imply a reduction in mucosal damage due to anti-inflammatory and anti-apoptotic effects of melatonin.

  6. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults.

    PubMed

    Turner, Kevin O; Sinkre, Richa A; Neumann, William L; Genta, Robert M

    2017-02-01

    The normal content of eosinophils in the adult colon and the criteria for the histopathologic diagnosis of eosinophilic colitis remain undefined. This study aimed at: (1) establishing the numbers of eosinophils in the normal adult colon; and (2) proposing a clinicopathologic framework for the diagnosis of primary colonic eosinophilia and eosinophilic colitis. To accomplish these goals, we counted the eosinophils in the right, transverse, and left colon of 159 adults with normal colonic histology. Using a database of 1.2 million patients with colonic biopsies, we extracted all adults with a diagnosis of colonic eosinophilia. We reviewed the slides from all cases and captured demographic, clinical, and pathologic data, including information about eosinophilia in other organs. We then compared the clinical manifestations of the study patients (those with no identifiable cause of eosinophilia) to those of patients with other types of colitis. The normal eosinophil counts (per mm) were 55.7±23.4 in the right, 41.0±18.6 in the transverse, and 28.6±17.2 in the left colon. Of the 194 study patients (eosinophil counts 166-5050/mm), 63 were asymptomatic and had a normal colonoscopy. Diarrhea and abdominal pain were the commonest indications for colonoscopy (38% and 27%, respectively) among the 131 patients who had symptoms, endoscopic abnormalities, or both. Neither clinical manifestations nor endoscopic appearance were sufficiently characteristic to elicit the suspicion of colonic eosinophilia. In conclusion, primary colonic eosinophilia was extremely rare in this series (<1 in 6000 patients); one third of these patients were asymptomatic. Their clinical manifestations were not distinctive and could not have led clinicians to suspect this condition; one third of the patients were asymptomatic. We suggest that regularly reporting high colonic eosinophilia may result in increased opportunities for clinicopathologic studies that might lead to a better definition of this

  7. [Anti-TNF-alpha therapy in ulcerative colitis].

    PubMed

    Lakatos, Péter László; Lakatos, László

    2008-05-18

    The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.

  8. Pseudomembranous colitis following bortezomib therapy in a myeloma patient.

    PubMed

    Moon, Sung-Jin; Min, Chang-Ki; Lee, Dong-Gun; Lee, Seok; Lee, Jong-Wook; Min, Woo-Sung; Kim, Chun-Choo; Kim, Myungshin; Park, Gyeongsin; Kim, Younggu

    2007-01-01

    The proteasome inhibitor, bortezomib, has antimyeloma activity even in myeloma cells refractory to multiple prior treatments. The most commonly reported adverse events in patients receiving bortezomib are sensory neuropathy, thrombocytopenia and gastrointestinal events. We report a patient with myeloma who developed pseudomembranous colitis after bortezomib treatment. Bortezomib has the boronic acid moiety which improves the specificity of proteasome inhibition and can be used as non-beta-lactam-based beta-lactamase inhibitors. This case indicates that gastrointestinal toxicities by bortezomib may be caused, in part, as a result of change in the colonization of colonic microflora.

  9. Ulcerative Colitis: Current Treatment Strategies and Future Prospects

    PubMed Central

    Peppercorn, Mark A.

    2009-01-01

    Ulcerative colitis (UC) is a disease of unknown etiology characterized by inflammation of the mucosa and occasionally the submucosa of the colon. Conventional drug therapy for UC involves use of aminosalicylates, corticosteroids, azathioprine/6-mercaptopurine, cyclosporine and anti-tumor necrosis factor therapy. Alternative therapies include probiotics, nicotine and fish oil. Drugs like tacrolimus, rosiglitazone and Trichuris suis ova are being evaluated for use in UC patients. With the new biologic agents, new treatment options for UC continue to evolve. In this article we will discuss the conventional drugs, the alternative therapies and the management strategies according to the severity and extent of UC. PMID:21180538

  10. Ulcerative colitis: current treatment strategies and future prospects.

    PubMed

    Garud, Sagar; Peppercorn, Mark A

    2009-03-01

    Ulcerative colitis (UC) is a disease of unknown etiology characterized by inflammation of the mucosa and occasionally the submucosa of the colon. Conventional drug therapy for UC involves use of aminosalicylates, corticosteroids, azathioprine/6-mercaptopurine, cyclosporine and anti-tumor necrosis factor therapy. Alternative therapies include probiotics, nicotine and fish oil. Drugs like tacrolimus, rosiglitazone and Trichuris suis ova are being evaluated for use in UC patients. With the new biologic agents, new treatment options for UC continue to evolve. In this article we will discuss the conventional drugs, the alternative therapies and the management strategies according to the severity and extent of UC.

  11. Prevention of colitis-associated colorectal cancer with 8-hydroxydeoxyguanosine.

    PubMed

    Ock, Chan Young; Kim, Eun-Hee; Hong, Hua; Hong, Kyung Sook; Han, Young-Min; Choi, Ki-Seok; Hahm, Ki-Baik; Chung, Myung-Hee

    2011-09-01

    Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC.

  12. Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

    PubMed

    Rumessen, J J; Vanderwinden, J-M; Horn, T

    2010-10-01

    Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.

  13. Irritable Bowel Syndrome and Microscopic Colitis: A Systematic Review and Meta-analysis.

    PubMed

    Kamp, Eline J C A; Kane, John S; Ford, Alexander C

    2016-05-01

    Patients with microscopic colitis and patients with irritable bowel syndrome (IBS) present with similar symptoms. We examined the association between IBS and microscopic colitis in a systematic review and meta-analysis. We searched the medical literature to identify cross-sectional surveys or case-control studies reporting the association between microscopic colitis and IBS in 50 or more unselected adult patients. We recorded the prevalence of IBS symptoms in patients with histologically confirmed microscopic colitis, or the prevalence of histologically confirmed microscopic colitis in patients with IBS. Data were pooled using a random-effects model; the association between microscopic colitis and IBS was summarized using an odds ratio (OR) with a 95% confidence interval (CI). The search strategy identified 3926 citations, of which 10 were eligible for our analysis. The pooled prevalence of IBS in patients with microscopic colitis was 33.4% (95% CI, 31.5%-40.6%), but was not significantly higher in patients with microscopic colitis than in patients with diarrhea (OR, 1.39; 95% CI, 0.43-4.47). In 3 cross-sectional surveys, the pooled OR for microscopic colitis in participants with IBS, compared with other patients with diarrhea, was 0.68 (95% CI, 0.44-1.04). In 4 case-control studies the prevalence of IBS in patients with microscopic colitis was significantly higher than in asymptomatic controls (OR, 5.16; 95% CI, 1.32-20.2). Based on a meta-analysis, one third of patients with microscopic colitis reported symptoms compatible with IBS, but the prevalence of IBS was no higher than in other patients with diarrhea. The odds of microscopic colitis were no higher in patients with IBS compared with other patients with diarrhea. The value of routine colonoscopy and biopsy to exclude microscopic colitis in patients with typical IBS symptoms, unless other risk factors or alarm symptoms are present, remains uncertain. Copyright © 2016 AGA Institute. Published by Elsevier Inc

  14. Protective effect of alpha-lipoic acid, aerobic or resistance exercise from colitis in second hand smoke exposed young rats.

    PubMed

    Özbeyli, Dilek; Berberoglu, Ayşe Cansu; Özen, Anıl; Erkan, Oktay; Başar, Yunus; Şen, Tunahan; Akakın, Dilek; Yüksel, Meral; Kasımay Çakır, Özgür

    2017-01-01

    The role of second hand smoke (SHS) exposure on ulcerative colitis is not known. Our aim was to examine the effects of α-lipoic acid (ALA), chronic aerobic (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague-Dawley male rats (150-200 g, n=54) were selected for colitis induction. Among the colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the other was not. The SHS group was divided into subgroups as follows: sedentary; AE (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis was induced by intrarectal acetic acid. All groups had subgroups that were given subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and Student's t-test were used for statistical analysis. The increased macroscopic and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis and SHS-colitis groups were decreased via ALA (P<.05-.001). AE declined macroscopic and microscopic scores, MDA, lucigenin compared to colitis and SHS-colitis groups (P<.01-.001). RE reduced microscopic score, MPO, MDA, luminol, lucigenin (P<.05-.001) that were increased with colitis. Decreased GSH levels (P<.01) in the SHS-colitis group approached to control levels when given ALA. According to our results SHS and colitis induction increased inflammatory damage. SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE might be protective for SHS exposed ulcerative colitis conditions. © 2016 John Wiley & Sons Australia, Ltd.

  15. Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis

    PubMed Central

    McBee, Megan E.; Zeng, Yu; Parry, Nicola; Nagler, Cathryn R.; Tannenbaum, Steven R.

    2010-01-01

    Background Diagnosis of chronic intestinal inflammation, which characterizes inflammatory bowel disease (IBD), along with prediction of disease state is hindered by the availability of predictive serum biomarker. Serum biomarkers predictive of disease state will improve trials for therapeutic intervention, and disease monitoring, particularly in genetically susceptible individuals. Chronic inflammation during IBD is considered distinct from infectious intestinal inflammation thereby requiring biomarkers to provide differential diagnosis. To address whether differential serum biomarkers could be identified in murine models of colitis, immunological profiles from both chronic spontaneous and acute infectious colitis were compared and predictive serum biomarkers identified via multivariate modeling. Methodology/Principal Findings Discriminatory multivariate modeling of 23 cytokines plus chlorotyrosine and nitrotyrosine (protein adducts from reactive nitrogen species and hypochlorite) in serum and tissue from two murine models of colitis was performed to identify disease-associated biomarkers. Acute C. rodentium-induced colitis in C57BL/6J mice and chronic spontaneous Helicobacter-dependent colitis in TLR4−/− x IL-10−/− mice were utilized for evaluation. Colon profiles of both colitis models were nearly identical with chemokines, neutrophil- and Th17-related factors highly associated with intestinal disease. In acute colitis, discriminatory disease-associated serum factors were not those identified in the colon. In contrast, the discriminatory predictive serum factors for chronic colitis were neutrophil- and Th17-related factors (KC, IL-12/23p40, IL-17, G-CSF, and chlorotyrosine) that were also elevated in colon tissue. Chronic colitis serum biomarkers were specific to chronic colitis as they were not discriminatory for acute colitis. Conclusions/Significance Immunological profiling revealed strikingly similar colon profiles, yet distinctly different serum

  16. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system.

    PubMed

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-03-03

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18

  17. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system

    PubMed Central

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-01-01

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C18:1-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C18:1-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C18:1-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C18:1-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C18:1-ceramide, a

  18. Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis.

    PubMed

    Fujimoto, Yasuyuki; Azuma, Yasu-Taka; Matsuo, Yukiko; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Miki, Mariko; Azuma, Naoki; Teramoto, Midori; Nishiyama, Kazuhiro; Izawa, Takeshi; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2017-03-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.

  19. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

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

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

    2015-01-01

    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.

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

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

    2015-01-01

    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. PMID:26713317

  2. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-09-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.

  3. Drug consumption and additional risk factors associated with microscopic colitis: Case-control study.

    PubMed

    Guagnozzi, Danila; Lucendo, Alfredo J; Angueira, Teresa; González-Castillo, Sonia; Tenías, José María

    2015-06-01

    Microscopic colitis has now emerged as a common cause of chronic diarrhoea, but its aetiology remains unknown. Some studies suggest that commonly prescribed drugs and other additional risk factors may be triggers. To evaluate the effects of drug intake and other risk factors on microscopic colitis patients. A prospective, case-control study with all consecutive adult patients referred to the Hospital General de Tomelloso (Ciudad Real, Spain) for chronic watery diarrhoea (from 2008 to 2011) was performed. Microscopic colitis was diagnosed following the commonly accepted histopathological criteria. 46 consecutive new cases of microscopic colitis and 317 chronic diarrhoea controls were recruited. Five independent risk factors significantly associated with microscopic colitis were identified: Abdominal pain (OR 3.25; 95%CI, 1.49-7.08), weight loss (OR 2.67; 95%CI, 1.16-6.15), celiac disease (OR 15.3; 95%CI, 3.70-63.5), topiramate intake (OR 13.6; 95%CI, 1.84- 100.8), and older age at diagnosis (OR 1 year increase 1.022; 95%CI, 1.002-1.042). Use of non-steroidal anti-inflammatory drugs was associated with microscopic colitis in the subgroup of patients who fulfilled irritable bowel syndrome criteria (38.5% vs. 10.8%; p < 0.017). Microscopic colitis is associated with autoimmune disease, an increased age at diagnosis, topiramate intake and only in a sub-group of irritable bowel disease patients with non-steroidal anti-inflammatory drugs.

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

    PubMed

    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.

  5. Cancer surveillance of patients with longstanding ulcerative colitis: a clinical, endoscopical, and histological study.

    PubMed Central

    Broström, O; Löfberg, R; Ost, A; Reichard, H

    1986-01-01

    An eight year endoscopical and histological cancer surveillance programme comprising 71 patients with ulcerative colitis is presented. Forty one patients had total colitis and 30 substantial colitis. Mean duration of the disease was 19.7 years (range 9-46 years). An average of 2.6 colonoscopies per patient in the total colitis group were carried out, and at least two biopsies were taken at 10 locations in the colon. In the total colitis group, seven had either low (four), or high grade dysplasia (two), or Dukes' A cancer (one). In the group with substantial colitis two patients with low grade dysplasia were found. Dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having had total colitis for 25 to 44 years. The dysplasia and cancer findings at the colonoscopy preceding surgery corresponded well with the surgical specimens. In three operated patients a sequence of dysplasia development was recorded. With the exception of long duration and dysplasia, nothing in the clinical course distinguished the operated cases. Using this surveillance programme prophylactic colectomy can be limited to patients in a high risk group developing dysplasia. The risk of missing a cancer before it becomes incurable seems to be low. PMID:3804019

  6. Interleukin 10 gene transfer prevents experimental colitis in rats

    PubMed Central

    Barbara, G; Xing, Z; Hogaboam, C; Gauldie, J; Collins, S

    2000-01-01

    BACKGROUND—The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results.
AIMS—To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats.
METHODS—Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations.
RESULTS—Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect.
CONCLUSIONS—Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.


Keywords: gene therapy; colitis; interleukin 10; adenovirus vector; leukotrienes; inflammatory bowel disease; maintenance therapy PMID:10673295

  7. Ulcerative colitis with inflammatory polyposis in a teenage boy: A case report

    PubMed Central

    Feng, Jin-Shan; Ye, Ying; Guo, Can-Can; Luo, Bo-Tao; Zheng, Xue-Bao

    2015-01-01

    Ulcerative colitis in addition to inflammatory polyposis is common. The benign sequel of ulcerative colitis can sometimes mimic colorectal carcinoma. This report describes a rare case of inflammatory polyposis with hundreds of inflammatory polyps in ulcerative colitis which was not easy to distinguish from other polyposis syndromes. A 16-year-old Chinese male suffering from ulcerative colitis for 6 mo underwent colonoscopy, and hundreds of polyps were observed in the sigmoid, causing colonic stenosis. The polyps were restricted to the sigmoid. Although rectal inflammation was detected, no polyps were found in the rectum. A diagnosis of inflammatory polyposis and ulcerative colitis was made. The patient underwent total colectomy and ileal pouch anal anastomosis. The patient recovered well and was discharged on postoperative day 8. Endoscopic surveillance after surgery is crucial as ulcerative colitis with polyposis is a risk factor for colorectal cancer. Recognition of polyposis requires clinical, endoscopic and histopathologic correlation, and helps with chemoprophylaxis of colorectal cancer, as the drugs used postoperatively for colorectal cancer, ulcerative colitis and polyposis are different. PMID:25624746

  8. Infliximab for the treatment of ulcerative colitis: outcomes in Oxford from 2000 to 2006.

    PubMed

    Jakobovits, S L; Jewell, D P; Travis, S P L

    2007-05-01

    Infliximab has been shown to be of benefit in the treatment of ulcerative colitis but long-term colectomy rates remain unknown. To review the rate of colectomy after infliximab for ulcerative colitis and to identify factors that might predict the need for colectomy. We conducted a retrospective cohort study of patients with active ulcerative colitis treated with infliximab between 2000 and 2006. The primary outcome was colectomy-free survival. Disease and treatment characteristics and complications were documented. Thirty patients were treated with infliximab for refractory ulcerative colitis. Sixteen (53%) came to colectomy a median of 140 days after their first infusion (range 4-607). There was no difference in colectomy between those receiving infliximab for acute severe ulcerative colitis failing intravenous steroids (8/14) and out-patients with steroid-refractory ulcerative colitis (8/16). Only 17% (5/30) achieved a steroid-free remission after a median follow-up of 13 months (range 2-72). Univariate analysis showed that a younger age at diagnosis of colitis was significantly associated with an increased rate of colectomy (27.5 years vs. 38.7 years, P = 0.016). Over half the patients studied came to colectomy. Of those avoiding colectomy, only five (17%) sustained a steroid-free remission.

  9. Ulcerative colitis with inflammatory polyposis in a teenage boy: a case report.

    PubMed

    Feng, Jin-Shan; Ye, Ying; Guo, Can-Can; Luo, Bo-Tao; Zheng, Xue-Bao

    2015-01-21

    Ulcerative colitis in addition to inflammatory polyposis is common. The benign sequel of ulcerative colitis can sometimes mimic colorectal carcinoma. This report describes a rare case of inflammatory polyposis with hundreds of inflammatory polyps in ulcerative colitis which was not easy to distinguish from other polyposis syndromes. A 16-year-old Chinese male suffering from ulcerative colitis for 6 mo underwent colonoscopy, and hundreds of polyps were observed in the sigmoid, causing colonic stenosis. The polyps were restricted to the sigmoid. Although rectal inflammation was detected, no polyps were found in the rectum. A diagnosis of inflammatory polyposis and ulcerative colitis was made. The patient underwent total colectomy and ileal pouch anal anastomosis. The patient recovered well and was discharged on postoperative day 8. Endoscopic surveillance after surgery is crucial as ulcerative colitis with polyposis is a risk factor for colorectal cancer. Recognition of polyposis requires clinical, endoscopic and histopathologic correlation, and helps with chemoprophylaxis of colorectal cancer, as the drugs used postoperatively for colorectal cancer, ulcerative colitis and polyposis are different.

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

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    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. PMID:26218284

  11. Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Spp.

    PubMed Central

    Nguyen, Deanna D.; Muthupalani, Suresh; Goettel, Jeremy A.; Eston, Michelle A.; Mobley, Melissa; Taylor, Nancy S.; McCabe, Amanda; Marin, Romela; Snapper, Scott B.; Fox, James G.

    2014-01-01

    Background Wiskott-Aldrich Syndrome protein (WASP)-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which, Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in WASP-deficient (WKO) mice. Methods Feces from WKO mice raised under specific pathogen free conditions were evaluated for the presence of Helicobacter spp., after which, a subset of mice were rederived in Helicobacter spp.-free conditions. Helicobacter spp.-free WKO animals were subsequently infected with Helicobacter bilis. Results Helicobacter spp. were detected in feces from WKO mice. After re-derivation in Helicobacter spp.-free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on WASP-deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis-infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. Conclusions Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.-free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa. PMID:23820270

  12. Role of metallothioneins as danger signals in the pathogenesis of colitis.

    PubMed

    Devisscher, Lindsey; Hindryckx, Pieter; Lynes, Michael A; Waeytens, Anouk; Cuvelier, Claude; De Vos, Filip; Vanhove, Christian; Vos, Martine De; Laukens, Debby

    2014-05-01

    Inflammatory bowel diseases (IBDs) are recurrent intestinal pathologies characterized by a compromised epithelial barrier and an exaggerated immune activation. Mediators of immune cell infiltration may represent new therapeutic opportunities. Metallothioneins (MTs) are stress-responsive proteins with immune-modulating functions. Metallothioneins have been linked to IBDs, but their role in intestinal inflammation is inconclusive. We investigated MT expression in colonic biopsies from IBDs and acute infectious colitis patients and healthy controls and evaluated MT's role in experimental colitis using MT knockout mice and anti-MT antibodies. Antibody potential to target extracellular MT and its mechanism was tested in vitro. Biopsies of patients with active colitis showed infiltration of MT-positive cells in a pattern that correlated with the grade of inflammation. MT knockout mice displayed less severe acute dextran sulphate sodium (DSS)-induced colitis compared to congenic wild-type mice based on survival, weight loss, colon length, histological inflammation and leukocyte infiltration. Chronic DSS-colitis confirmed that Mt1 and Mt2 gene disruption enhances clinical outcome. Blockade of extracellular MT with antibodies reduced F4/80-positive macrophage infiltration in DSS- and trinitrobenzene sulphonic acid-colitis, with a tendency towards a better outcome. Whole-body single-photon emission computer tomography of mice injected with radioactive anti-MT antibodies showed antibody accumulation in the colon during colitis and clearance during recovery. Necrotic and not apoptotic cell death resulted in western blot MT detection in HT29 cell supernatant. In a Boyden chamber migration assay, leukocyte attraction towards the necrotic cell supernatant could be abolished with anti-MT antibody, indicating the chemotactic potential of endogenous released MT. Our results show that human colitis is associated with infiltration of MT-positive inflammatory cells. Since antibody

  13. Divergent influence of microRNA-21 deletion on murine colitis phenotypes.

    PubMed

    Wu, Feng; Dong, Fengshi; Arendovich, Nikolai; Zhang, Jing; Huang, Yong; Kwon, John H

    2014-11-01

    MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functions of miRNAs in murine colitis facilitates elucidating the role of specific miRNAs in human IBD. We aimed to determine the miRNA signature of several models of colitis and to assess the influence of miR-21 on intestinal inflammation. miR-21-deficient mouse and littermate controls were assessed in the standard DSS, TNBS, and CD4+ T-cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RB High cells were analyzed by miRNA and mRNA microarray, and quantitative reverse transcription polymerase chain reaction. T helper (Th) cell polarization was accessed by flow cytometry and enzyme-linked immunosorbent assay. Alterations in miRNA expression were identified for acute and chronic DSS and TNBS colitis, respectively. The expression of miRs-21, -142-3p, and -223 were distinct between DSS and TNBS models while overlap of numerous miRNAs was found. Importantly, miRs-19b, -192, and -215, that are decreased in IBD, were decreased in these models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis. Furthermore, the deletion of miR-21 resulted in the exacerbation of both the TNBS and T-cell transfer models of colitis. CD4+CD45RB High T cells from miR-21 mice were prone to Th1 polarization. MiRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21-/- deletion exacerbated CD4+ T-cell-mediated models of colitis provide further evidence that miRNAs play significant roles in the pathogenesis of IBD.

  14. Interaction of Ethnicity and H. pylori Infection in the Occurrence of Microscopic Colitis.

    PubMed

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

    2017-04-01

    Previous studies found that microscopic colitis is inversely associated with Helicobacter pylori infection and that microscopic colitis is characterized by a marked ethnic variation. The aim of the present study was to test whether an underlying ethnic variation of H. pylori infection is responsible for the ethnic variation of microscopic colitis. The Miraca Life Sciences Database is a large national electronic repository of histopathologic records of patients distributed throughout the entire USA. A cross-sectional study evaluated the influence of age, gender, ethnicity, and histologic diagnosis of H. pylori on the occurrence of microscopic colitis among subjects who underwent esophago-gastro-duodenoscopies plus colonoscopy. The total study population comprised 228,506 subjects, of whom 28,890 carried a diagnosis of H. pylori gastritis and 3460 microscopic colitis. Female sex, old age, and H. pylori infection exerted the strongest influence on the occurrence of microscopic colitis. In comparison with the population comprising Caucasians and African-Americans, microscopic colitis was less common among subjects of Hispanic (0.34, 0.27-0.47), East Asian (0.13, 0.06-0.22), Indian (0.31, 0.10-0.73), or Middle Eastern descent (0.28, 0.07-0.74). All these ethnic subgroups were also characterized by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of microscopic colitis (R (2) = 0.91, p < 0.001). Ethnic variations in the gastric infection with H. pylori may be partly responsible for the observed ethnic distribution of microscopic colitis.

  15. Histopathologic Features of Colitis Due to Immunotherapy With Anti-PD-1 Antibodies.

    PubMed

    Chen, Jonathan H; Pezhouh, Maryam K; Lauwers, Gregory Y; Masia, Ricard

    2017-05-01

    Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis. We describe here the histopathologic findings in 8 patients who developed colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt atrophy/dropout. These latter features are reminiscent of other colitides with prominent apoptosis such as acute graft-versus-host disease or certain drug-induced colitides. The remainder of cases (3/8) showed a lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1 colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1 colitis. Interestingly, recurrent colitis was observed in patients who had been off anti-PD-1 therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1 colitis among pathologists, to facilitate its timely diagnosis

  16. The Unfolded Protein Response and Chemical Chaperones Reduce Protein Misfolding and Colitis in Mice

    PubMed Central

    CAO, STEWART SIYAN; ZIMMERMANN, ELLEN M.; CHUANG, BRANDY–MENGCHIEH; SONG, BENBO; NWOKOYE, ANOSIKE; WILKINSON, J. ERBY; EATON, KATHRYN A.; KAUFMAN, RANDAL J.

    2013-01-01

    BACKGROUND & AIMS Endoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress–induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis. METHODS We used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6α or the protein chaperone P58IPK. We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58IPK−/−, and Atf6α−/− mice with colitis; and in Il10−/− mice. RESULTS P58IPK−/− and Atf6α−/− mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58IPK−/− mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6α−/− mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10−/− mice, and DSS-induced colitis in P58IPK−/− and Atf6α−/− mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells. CONCLUSIONS The unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases. PMID:23336977

  17. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis.

    PubMed

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I Metin; Sutcu, Recep

    2016-09-01

    Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD.

  18. Creatine maintains intestinal homeostasis and protects against colitis

    PubMed Central

    Turer, Emre; McAlpine, William; Wang, Kuan-wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R.; Beutler, Bruce

    2017-01-01

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea–mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury. PMID:28137860

  19. Second Korean guidelines for the management of ulcerative colitis

    PubMed Central

    Choi, Chang Hwan; Moon, Won; Kim, You Sun; Kim, Eun Soo; Lee, Bo-In; Jung, Yunho; Yoon, Yong Sik; Lee, Heeyoung; Park, Dong Il

    2017-01-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations. PMID:28239313

  20. A case of reactive arthritis due to Clostridium difficile colitis

    PubMed Central

    Essenmacher, Alex C.; Khurram, Nazish; Bismack, Gregory T.

    2016-01-01

    Reactive arthritis is an acute, aseptic, inflammatory arthropathy following an infectious process but removed from the site of primary infection. It is often attributed to genitourinary and enteric pathogens, such as Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia, in susceptible individuals. An uncommon and less recognized cause of this disease is preceding colonic infection with Clostridium difficile, an organism associated with pseudomembranous colitis and diarrhea in hospitalized patients and those recently exposed to antibiotics. Recognition of this association may be complicated by non-specific presentation of diarrhea, the interval between gastrointestinal and arthritic symptoms, and the wide differential in mono- and oligoarthritis. We present the case of a 61-year-old, hospitalized patient recently treated for C. difficile colitis who developed sudden, non-traumatic, right knee pain and swelling. Physical examination and radiographs disclosed joint effusion, and sterile aspiration produced cloudy fluid with predominant neutrophils and no growth on cultures. Diagnostic accuracy is enhanced by contemporaneous laboratory investigations excluding other entities such as gout and rheumatoid arthritis and other infections that typically precede reactive arthritis. Contribution of Clostridium infection to reactive arthritis is an obscure association frequently difficult to prove, but this organism is warranted inclusion in the differential of reactive arthritis. PMID:26908381

  1. Clostridium difficile colitis in children following lung transplantation.

    PubMed

    Rosen, J B; Schecter, M G; Heinle, J S; McKenzie, E D; Morales, D L; Dishop, M K; Danziger-Isakov, L; Mallory, G B; Elidemir, O

    2010-08-01

    Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.

  2. Eosinophilic Colitis: University of Minnesota Experience and Literature Review

    PubMed Central

    Gaertner, Wolfgang B.; MacDonald, Jennifer E.; Kwaan, Mary R.; Shepela, Christopher; Madoff, Robert; Jessurun, Jose; Melton, Genevieve B.

    2011-01-01

    Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal). The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders). Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults) presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 2–48) months. PMID:21837236

  3. Cytokine networks in animal models of colitis-associated cancer.

    PubMed

    Antoniou, Efstathios; Margonis, Georgios Antonios; Angelou, Anastasios; Zografos, George C; Pikoulis, Emmanouil

    2015-01-01

    It is well-known that inflammatory bowel disease (IBD) poses an increased, yet not definitely estimated, risk of colitis-associated colon cancer (CAC), which is considered a more aggressive and distinct in both genetic and molecular levels clinical entity compared to sporadic colorectal cancer (CRC). The present review discusses the cytokine networks involved in CAC-based translational findings from suitable animal models of the disease. Moreover, we summarize the most prominent data concerning the role of Th1, Th2, Th17 and anti-inflammatory cytokines in the pathogenesis of CAC. Last, we briefly address the controversies between basic science findings in IBD and CAC and suggest further directions regarding research on cytokines. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of cytokines in the context of CAC. The MEDLINE database was thoroughly searched using the keywords: cytokines, colitis-associated cancer, animal models, carcinogenesis. Additional articles were gathered and evaluated. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility.

    PubMed

    Li, Pingping; Shi, Junxiu; Zhang, Peng; Wang, Ke; Li, Jinglong; Liu, Hongju; Zhou, Yu; Xu, Xi; Hao, Jie; Sun, Xiuyuan; Pang, Xuewen; Li, Yan; Wu, Hounan; Chen, Xiaoping; Ge, Qing

    2015-08-01

    The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.

  5. Infrared spectroscopy as a screening technique for colitis

    NASA Astrophysics Data System (ADS)

    Titus, Jitto; Ghimire, Hemendra; Viennois, Emilie; Merlin, Didier; Perera, A. G. Unil

    2017-05-01

    There remains a great need for diagnosis of inflammatory bowel disease (IBD), for which the current technique, colonoscopy, is not cost-effective and presents a non-negligible risk for complications. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy is a new screening technique to evaluate colitis. Comparing infrared spectra of sera to study the differences between them can prove challenging due to the complexity of its biological constituents giving rise to a plethora of vibrational modes. Overcoming these inherent infrared spectral analysis difficulties involving highly overlapping absorbance peaks and the analysis of the data by curve fitting to improve the resolution is discussed. The proposed technique uses colitic and normal wild type mice dried serum to obtain ATR/FTIR spectra to effectively differentiate colitic mice from normal mice. Using this method, Amide I group frequency (specifically, alpha helix to beta sheet ratio of the protein secondary structure) was identified as disease associated spectral signature in addition to the previously reported glucose and mannose signatures in sera of chronic and acute mice models of colitis. Hence, this technique will be able to identify changes in the sera due to various diseases.

  6. Achilles tendinitis as a rare extraintestinal manifestation of ulcerative colitis.

    PubMed

    Zenda, Takahiro; Araki, Ichiro; Nakamiya, Otoyuki; Tokuumi, Yuji; Shimada, Yuka; Komai, Keigo; Taniuchi, Yukie

    2016-06-01

    Patients with inflammatory bowel disease often have extraintestinal manifestations (EIMs) involving almost all organ systems, but little has been reported on Achilles tendinitis. Herein, we present a unique case of Achilles tendinitis, which manifested shortly after initiation of mesalazine therapy for ulcerative colitis. A 26-year-old Japanese woman with bloody diarrhea and abdominal cramps lasting for 7 days was referred to our hospital. The Lichtiger clinical activity index (CAI) score was 9 at the first visit. Based on the clinical symptoms and examination results, she was diagnosed with ulcerative pancolitis in the active phase, and treatment with mesalazine (2.4 g/day) and probiotics was initiated. Her symptoms resolved within 7 days of treatment (CAI 3). However, she then developed bilateral Achilles tendinitis without any apparent cause. The Achilles tendinitis subsided with conservative management within 2 weeks, despite continuation of mesalazine therapy. This case instructively suggests that Achilles tendinitis should be noted as an EIM of ulcerative colitis.

  7. Ipilimumab-Induced Enteritis without Colitis: A New Challenge

    PubMed Central

    Messmer, Marcus; Upreti, Sunita; Tarabishy, Yaman; Mazumder, Nikhilesh; Chowdhury, Reezwana; Yarchoan, Mark; Holdhoff, Matthias

    2016-01-01

    Introduction Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4), approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. Case Report An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days. One month prior, he had started treatment with ipilimumab for metastatic melanoma. On presentation, he was found to have severe electrolyte disturbances, including hyponatremia, hypokalemia, and acute kidney injury. Causes of infectious diarrhea were excluded, and he was treated with corticosteroids for presumed ipilimumab-associated enterocolitis. However, colonoscopy revealed normal mucosa, both grossly and on pathology of random biopsies. Steroids were weaned but his symptoms recurred. He then underwent upper endoscopy with enteroscopy. Biopsy of the duodenum was notable for acute inflammation, villous blunting, and other changes consistent with ipilimumab-associated injury. He was restarted on high-dose steroids and his symptoms resolved. Discussion Ipilimumab-induced enteritis is a serious and potentially life-threatening immune related adverse event that warrants prompt recognition and aggressive management. As in cases of ipilimumab-associated enterocolitis, steroids are an effective therapy. Enteritis without colitis should be suspected in patients on ipilimumab who present with severe diarrhea but have a normal colonoscopy. PMID:27920706

  8. Cellulose Supplementation Early in Life Ameliorates Colitis in Adult Mice

    PubMed Central

    Nagy-Szakal, Dorottya; Hollister, Emily B.; Luna, Ruth Ann; Szigeti, Reka; Tatevian, Nina; Smith, C. Wayne; Versalovic, James; Kellermayer, Richard

    2013-01-01

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC]) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS) colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001]), and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]). Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation. PMID:23437211

  9. Nicotine: therapeutic potential for the treatment of ulcerative colitis.

    PubMed

    Green, J T; Thomas, G A; Rhodes, J

    1997-01-01

    Ulcerative colitis (UC) is predominantly a disease of non-smokers, and nicotine may be the agent responsible for this association. Transdermal nicotine has been shown to improve disease activity and sigmoidoscopic appearance in the active disease but in one study had no effect on maintenance of remission. Since side-effects with nicotine patches occur in up to two thirds of patients, attempts to reduce systemic levels and improve drug tolerance have been developed with colonic delivery systems of nicotine. Preliminary observations with nicotine enemas in UC have shown clinical benefit, but controlled trials are needed. Mechanisms responsible for the association of smoking with colitis and for the therapeutic effect of nicotine remain an enigma; possibilities include: modulation of the immune response, alterations of colonic mucus and eicosanoid production, changes in rectal blood flow, decreased intestinal permeability and the release of endogenous glucocorticoids. With current treatment for UC limited to corticosteroids and formulations of 5-aminosalicylic acid, alternative treatments are required and nicotine may fulfil this role.

  10. Review article: the long-term management of ulcerative colitis.

    PubMed

    Hanauer, S B

    2004-10-01

    After the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The 'optimal' maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate-induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long-term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long-term goals of maintenance therapy (e.g. prevention of relapse, reduction of long-term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti-inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.

  11. [Ulcerative colitis and amyloidosis. Presentation of a case and review of the literature].

    PubMed

    Triviño, A; Sánchez Lombraña, J L; Linares, A; Pérez, R; Herrero Zapatero, A; Rodrigo, L

    1992-08-01

    A case of ulcerative colitis associated with secondary amyloidosis in a 62-year-old man who died from septic shock and pneumonia complicating head injury is reported. Amyloid deposition was incidentally found at autopsy. Proteinuria and hepatomegaly discovered a few days before his death were the only signs of amyloidosis. The postmortem examination showed chronic ulcerative colitis (remitting form) with pseudo-polyps and amyloid deposition in the liver, spleen, pancreas, rectum, adrenals and kidneys. Although secondary amyloidosis complicating with Crohn's disease has been frequently reported, amyloidosis associated with ulcerative colitis has been exceptionally described and only 10 cases have been collected from the literature.

  12. Proteins and peptides: The need to improve them as promising therapeutics for ulcerative colitis.

    PubMed

    Sahu, Kantrol Kumar; Minz, Sunita; Kaurav, Monika; Pandey, Ravi Shankar

    2016-01-01

    The present review briefly describes the nature, type and pathogenesis of ulcerative colitis, and explores the potential use of peptides and proteins in the treatment of inflammatory bowel disease, especially ulcerative colitis. Intestinal absorption and the barrier mechanism of peptide and protein drugs are also discussed, with special emphasis on various strategies which make these drugs better therapeutics having high specificity, potency and molecular targeting ability. However, the limitation of such therapeutics are oral administration, poor pharmacokinetic profile and decreased bioavailability. The recent findings illustrated in this review will be helpful in designing the peptide/protein drugs as a promising treatment of choice for ulcerative colitis.

  13. Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation.

    PubMed

    Yates, B; Murphy, D M; Fisher, A J; Gould, F K; Lordan, J L; Dark, J H; Corris, P A

    2007-06-01

    Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.

  14. [Amebic colitis and amebic liver abscess--epidemiology and personal case report].

    PubMed

    Kassahun, W; Steinert, M; Schwokowski, C; Petzold, A; Emmrich, P

    1997-01-01

    The large intestine reacts relatively monomorphically to different stimuli. From this differential-diagnostic problems may result. The history of a patient is described which could be pursued clinically over 12 weeks and during the course of which the correction of the diagnosis ulcerative colitis into amoebic colitis was necessary. It is concluded that in every symptomatology of colitis bacterial and parasitologic examinations of the faeces should be performed primarily specially if there is a history of overseas travel. In these cases it must be also thought of spontaneous amoebic infections.

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

    PubMed Central

    Hale, Laura P; Cianciolo, George

    2008-01-01

    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 of TNF but may not

  16. Effectiveness of infliximab in the treatment of perianal fistulas in ulcerative colitis: report of two cases.

    PubMed

    de la Piscina, Patricia Ramírez; Duca, Ileana; Estrada, Silvia; Spicakova, Katerina; Calderón, Rosario; Urtasun, Leire; Marra-López, Carlos; Salvador, Marta; Delgado, Elvira; Campos, Francisco García

    2013-01-01

    Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiopathogenesis and increasing incidence in recent years. Perianal complications of ulcerative colitis are rare and seem to be associated with higher extent of inflammation and a more severe course of the disease. The cases of two male patients with severe corticoid-dependent ulcerative colitis of protracted clinical course who developed perianal fistulas and abscesses successfully treated with infliximab are reported. Treatment with infliximab was followed by perianal fistula closure with marked improvement in the quality of life over 2-year follow-up period.

  17. Effectiveness of infliximab in the treatment of perianal fistulas in ulcerative colitis: report of two cases

    PubMed Central

    de la Piscina, Patricia Ramírez; Duca, Ileana; Estrada, Silvia; Spicakova, Katerina; Calderón, Rosario; Urtasun, Leire; Marra-López, Carlos; Salvador, Marta; Delgado, Elvira; Campos, Francisco García

    2013-01-01

    Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiopathogenesis and increasing incidence in recent years. Perianal complications of ulcerative colitis are rare and seem to be associated with higher extent of inflammation and a more severe course of the disease. The cases of two male patients with severe corticoid-dependent ulcerative colitis of protracted clinical course who developed perianal fistulas and abscesses successfully treated with infliximab are reported. Treatment with infliximab was followed by perianal fistula closure with marked improvement in the quality of life over 2-year follow-up period. PMID:24714219

  18. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

    PubMed

    Komeno, Yukiko; Ogawa, Seishi; Ishida, Tateru; Takeuchi, Kengo; Tsujino, Shiho; Kurokawa, Mineo; Aoki, Katsunori; Kanda, Yoshinobu; Chiba, Shigeru; Motokura, Toru; Fukayama, Masashi; Hirai, Hisamaru

    2003-12-01

    Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

  19. The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression.

    PubMed

    Silva, Marcelo Jose Dias; Vilegas, Wagner; da Silva, Marcelo Aparecido; Paiotti, Ana Paula Ribeiro; Pastrelo, Mauricio Mercaldi; Ruiz, Pedro Luiz Menin; de Moura, Carolina Foot Gomes; Oshima, Celina Tizuko Fujiyama; Ribeiro, Daniel Araki

    2017-10-09

    The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 - Sham group:; G2 - TNBS group; G3, G4 -colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 - colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis

    PubMed Central

    Fukata, Masayuki; Shang, Limin; Santaolalla, Rebeca; Sotolongo, John; Pastorini, Cristhine; España, Cecilia; Ungaro, Ryan; Harpaz, Noam; Cooper, Harry S.; Elson, Greg; Kosco-Vilbois, Marie; Zaias, Julia; Perez, Maria T.; Mayer, Lloyd; Vamadevan, Arunan S.; Lira, Sergio A.; Abreu, Maria T.

    2010-01-01

    Chronic intestinal inflammation culminates in cancer and a link to TLR4 has been suggested by our observation that TLR4 deficiency prevents colitis-associated neoplasia. In the current study, we address the effect of the aberrant activation of epithelial TLR4 on induction of colitis and colitis-associated tumor development. We take a translational approach to address the consequences of increased TLR signaling in the intestinal mucosa. Mice transgenic for a constitutively-active TLR4 under the intestine-specific villin promoter (villin-TLR4 mice) were treated with DSS for acute colitis and azoxymethane-dextran sulfate sodium. TLR4 expression was analyzed by immunohistochemistry in colonic tissue from patients with ulcerative colitis and ulcerative colitis associated cancer. The effect of an antagonist TLR4 Ab was tested in prevention of colitis-associated neoplasia in the AOM-DSS model. Villin-TLR4 mice were highly susceptible to both acute colitis and colitis-associated neoplasia. Villin-TLR4 mice had increased epithelial expression of COX-2 and mucosal PGE2 production at baseline. Increased severity of colitis in villin-TLR4 mice was characterized by enhanced expression of inflammatory mediators and increased neutrophilic infiltration. In human UC samples, TLR4 expression was upregulated in almost all CAC and progressively increases with grade of dysplasia. As a proof of principle, a TLR4/MD-2 antagonist antibody inhibited colitis-associated neoplasia in the mouse model. Our results show that regulation of TLR's can affect the outcome of both acute colitis and its consequences—cancer. Targeting TLR4 and other TLR's may ultimately play a role in prevention or treatment of colitis-associated cancer. PMID:21674704

  1. Unfractionated Heparin and New Heparin Analogues from Ascidians (Chordate-Tunicate) Ameliorate Colitis in Rats*

    PubMed Central

    Belmiro, Celso L. R.; Castelo-Branco, Morgana T. L.; Melim, Leandra M. C.; Schanaider, Alberto; Elia, Celeste; Madi, Kalil; Pavão, Mauro S. G.; de Souza, Heitor S. P.

    2009-01-01

    The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-α, TGF-β, and VEGF was observed, as well as a reduction of NF-κB and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin. PMID:19258310

  2. Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice.

    PubMed

    Sasaki, Soichiro; Baba, Tomohisa; Shinagawa, Kei; Matsushima, Kouji; Mukaida, Naofumi

    2014-09-15

    Patients with inflammatory bowel diseases often develop colon carcinoma. Combined treatment of azoxymethane (AOM) and dextran sulfate sodium (DSS) recapitulates colitis-associated cancer in mice. AOM/DSS-induced tumor formation was reduced in CCL3- or its specific receptor, CCR5-deficient mice despite the presence of a massive infiltration of inflammatory cells. However, AOM/DSS-induced type I collagen-positive fibroblast accumulation in the colon was reduced in CCL3- or CCR5-deficient mice. This was associated with depressed expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is expressed mainly by fibroblasts. Moreover in vitro, CCL3 induced fibroblasts to proliferate and to enhance HB-EGF expression. Furthermore, CCR5 blockade reduced tumor formation together with reduced fibroblast accumulation and HB-EGF expression, even when administered after the development of multiple colon tumors. Thus, CCL3-CCR5-mediated fibroblast accumulation may be required, in addition to leukocyte infiltration, to induce full-blown colitis-associated carcinogenesis. Our studies shed light on a therapeutic potential of CCR5 antagonist for patients with colitis-associated cancer.

  3. Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

    PubMed Central

    Kim, Mi Na; Koh, Seong-Joon; Kim, Jung Mogg; Im, Jong Pil; Jung, Hyun Chae; Kim, Joo Sung

    2014-01-01

    AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease. METHODS: Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10-/-mice were stimulated for 4 h with C. difficile toxin A (200 μg/mL), and gene expression of interferon (IFN)-γ, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10-/- mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10-/-) were then challenged with oral administration of C. difficile (1 × 105 colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis. RESULTS: C. difficile toxin A treatment induced IFN-γ gene expression to a level that was significantly higher in BDMCs from IL-10-/- compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10-/- compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10-/- and WT mice. The histopathologic severity score was significantly higher in the IL-10-/- than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-γ gene expression in colonic tissues from IL-10-/- than from WT mice challenged with C. difficile (P < 0.05). CONCLUSION: These results indicate that colitis is more severe after C. difficile infection in IL-10-/-mice, and that IFN-γ expression is involved in this process. PMID:25493020

  4. /sup 111/Indium leucocyte scanning in ampicillin-associated right-sided hemorrhagic colitis

    SciTech Connect

    Keshavarzian, A.; Saverymuttu, S.H.; Chadwick, V.S.

    1984-07-01

    Hemorrhagic colitis is a rare but well-recognized complication with ampicillin or penicillin derivative treatment. Early colonoscopy has been advocated in establishing the diagnosis by demonstrating the characteristic pattern of only right-sided involvement and so distinguishing it from other colitides. The authors report a patient who developed colitis after amoxycillin therapy in whom /sup 111/Indium leucocyte scan demonstrated right-sided colitis which alerted them to the diagnosis. Discontinuation of the antibiotic resulting in rapid improvement, and return of the /sup 111/Indium leucocyte scan to normal in this patient suggests that ampicillin-associated colitis should not be considered purely as a hemorrhagic disease but may in some cases have an inflammatory component.

  5. Antioxidant properties of mesenchymal stem cells against oxidative stress in a murine model of colitis.

    PubMed

    da Costa Gonçalves, Fabiany; Grings, Mateus; Nunes, Natália Schneider; Pinto, Fernanda Otesbelgue; Garcez, Tuane Nerissa Alves; Visioli, Fernanda; Leipnitz, Guilhian; Paz, Ana Helena

    2017-04-01

    To investigate the effects of oxidative stress injury in dextran sulfate sodium (DSS)-induced colitis in mice treated with mesenchymal stem cells (MSC). Mice exposed to oral administration of 2% DSS over 7 days presented a high disease activity index and an intense colonic inflammation. Systemic infusion of MSC protected from severe colitis, reducing weight loss and diarrhea while lowering the infiltration of inflammatory cells. Moreover, toxic colitis injury increased oxidative stress. Administration of DSS decreased reduced glutathione (GSH) and superoxide dismutase (SOD) activity, and increased thiobarbituric acid-reactive substances levels in the colon. No alteration was found in catalase (CAT) and glutathione peroxidase (GPx) activity. Otherwise, MSC transplantation was able to prevent the decrease of GSH levels and SOD activity suggestive of an antioxidant property of MSC. The oxidative stress is a pathomechanism underlying the pathophysiology of colitis and MSC play an important role in preventing the impairment of antioxidants defenses in inflamed colon.

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

    PubMed Central

    Bhatt, Vijaya R.; Murukutla, Srujitha; DiPoce, Jason; Gustafson, Steven; Sarkany, David; Mody, Kokila; Widmann, Warren D.; Gottesman, Aaron

    2014-01-01

    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. PMID:24596650

  7. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

    PubMed

    Dubin, Krista; Callahan, Margaret K; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G; Wolchok, Jedd D

    2016-02-02

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.

  8. Colonic mucormycosis presented with ischemic colitis in a liver transplant recipient.

    PubMed

    Do, Gi Won; Jung, Seok Won; Jun, Jae-Bum; Seo, Jae Hee; Nah, Yang Won

    2013-06-14

    Mucormycosis is an uncommon opportunistic fungal infection with high mortality in liver transplant recipients. Mucormycosis of the gastrointestinal tract can manifest with features similar to ischemic colitis. Typically signs and symptoms of non-gangrenous ischemic colitis resolve spontaneously within 24-48 h. On the other hand, the clinical course of the mucormycosis is commonly fulminant. We encountered a case of invasive fungal colitis presenting with abdominal pain and hematochezia in a liver transplant recipient. Endoscopic examination showed multiple shallow ulcerations and edema with mucosal friabilities on the sigmoid and distal descending colon, which was consistent with ischemic colitis. However, the histological examination obtained from endoscopic biopsies showed fungal hyphae with surrounding inflammatory cells and mucosal necrosis. The patient was successfully managed with antifungal agent without surgical treatment. Thus, early diagnosis and treatment is essential for improving the prognosis of invasive fungal infection after liver transplantation.

  9. The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis.

    PubMed

    Birtwistle, J

    1996-12-01

    Epidemiological evidence suggests that ulcerative colitis is a disease of nonsmokers, while Crohn's disease is a disease of smokers. The relative risk of developing ulcerative colitis is not only greater in nonsmokers, in addition there appears to be a rebound effect in smokers who quit, with the heaviest (ex-)smokers increasing their relative risk of the disease the most. This factor poses an ethical dilemma for health professionals giving advice on stopping smoking, which may thus have a serious detrimental effect on the health of some patients. Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial effect and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.

  10. Preparation, characterization and anti-colitis activity of curcumin-asafoetida complex encapsulated in turmeric nanofiber.

    PubMed

    Gopi, Sreeraj; Amalraj, Augustine; Jude, Shintu; Varma, Karthik; Sreeraj, T R; Haponiuk, Józef T; Thomas, Sabu

    2017-12-01

    Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD). Asafoetida (ASF) and turmeric have traditionally been used for the treatment of various inflammatory diseases, including UC, because ASF is rich in sulfur compounds and turmeric contains curcumin (CUR). Turmeric nanofiber (TNF), the modified cell wall component of turmeric is considered to play important role in the human diet, health and can be used as a carrier agent to encapsulate bioactive components. A novel gut health product (GHP) was formulated by encapsulation of ASF and CUR complex onto TNF. The GHP was characterized by UPLC, GC-MS, FTIR, XRD, SEM with EDS and DSC studies. GHP was evaluated for anti-colitis activity in a rat model of 5% dextran sulfate sodium (DSS) induced UC. Treatment with GHP significantly attenuated the disease activity index, colitis score, histopathological changes and myeloperoxidase activity. GHP has significant protective effects against DSS induced colitis. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Intractable colitis associated with chronic granulomatous disease in a young girl.

    PubMed

    Yaman, Aytaç; Kuloğlu, Zarife; Doğu, Figen; İkincioğulları, Aydan; Ensari, Arzu; Çiftçi, Ergin; Kansu, Aydan

    2015-01-01

    Chronic granulomatous disease (CGD) is an autosomal recessive or X-linked disorder caused by NADPH oxidase deficiency leading to an impaired ability of reactive superoxide anion and metabolite formation and recurring severe bacterial and fungal infections, with a high mortality rate. Diarrhea, colitis, ileus, perirectal abscess formation and anal fissures are reported gastrointestinal findings in these patients. We report a case of intractable colitis associated with CGD in a young girl.

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

    PubMed Central

    Gupta, Ram; Chaudhary, Anita R; Shah, Binita N; Jadhav, Avinash V; Zambad, Shitalkumar P; Gupta, Ramesh Chandra; Deshpande, Shailesh; Chauthaiwale, Vijay; Dutt, Chaitanya

    2014-01-01

    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 ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD. PMID:24493931

  13. Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation.

    PubMed

    Yates, B; Murphy, D M; Fisher, A J; Gould, F K; Lordan, J L; Dark, J H; Corris, P A

    2009-01-01

    In the present study, 4 patients with cystic fibrosis undergoing lung transplantation (from a total of 137) who developed fulminant pseudomembranous colitis are described. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.

  14. Carcinoid tumor of the ileoanal pouch in a patient with ulcerative colitis.

    PubMed

    Resnick, Murray; Pricolo, Victor; Chen, Sonja

    2013-01-04

    Carcinoid tumors have been reported to occur in various locations, particularly in the gastrointestinal tract. The relationship between the development of carcinoids and ulcerative colitis has been an unclear and controversial one. The association of ulcerative colitis and the development of ileal-pouch carcinoids has not, however, been well documented. We report a case of carcinoid tumor arising in an ileoanal pouch and discuss its unique diagnostic and therapeutic considerations.

  15. Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

    PubMed Central

    Wang, Arthur; Fernando, Maria; Leung, Gabriella; Phan, Van; Smyth, David; McKay, Derek M.

    2010-01-01

    Substantial data show that infection with helminth parasites ameliorates colitis; however, oxazolone-induced colitis is exaggerated in mice infected with the tapeworm, Hymenolepis diminuta. We tested the hypothesis that the IL-5 response to helminth infection enhances the severity of oxazolone-induced colitis. Mice were infected with H. diminuta and 8 days later were treated with oxazolone ± anti–IL-5 antibodies. Colitis was assessed 72 hours postoxazolone treatment by disease activity scores, myeloperoxidase activity, and histopathology. Other mice received injections of a replication-deficient adenovirus that carried the IL-5 (Ad.IL-5) gene or a control adenovirus (Ad.delete) ± oxazolone. The effect of H. diminuta+oxazolone in CCL11/CCL22 (eotaxin-1 and 2) knockout (KO) mice was determined. Helminth infection and Ad.IL-5 treatment increased IL-5 and eosinophil numbers. In vivo neutralization of IL-5 significantly reduced the severity of colitis in H. diminuta+oxazolone-treated mice, and H. diminuta did not exaggerate oxazolone-induced colitis in CCL11/CCL22 KO mice. Mice receiving Ad.IL-5 only had no colitis, while oxazolone-induced colitis was more severe in animals cotreated with Ad.IL-5 (Ad.delete + oxazolone was not significantly different from oxazolone only). Thus, while there is much to be gleaned about antiinflammatory mechanisms from rodent-helminth model systems, these data illustrate the caveat that infection with helminth parasites as a therapy could be contraindicated in patients with eosinophilia or elevated IL-5 unless coupled to appropriate measures to block IL-5 and/or eosinophil activity. PMID:21037078

  16. Adoptive transfer of macrophage from mice with depression-like behavior enhances susceptibility to colitis.

    PubMed

    Ghia, Jean-Eric; Park, Amber J; Blennerhassett, Patricia; Khan, Waliul I; Collins, Stephen M

    2011-07-01

    Depression is common in patients with inflammatory bowel disease (IBD) but the pathway is not well understood. We examined whether the locus of susceptibility to colitis in mice with depression-like behavior (DLB) resides with the macrophage and implicates the vagus nerve. Chronic colitis mimicking ulcerative colitis (UC) was induced by dextran sulfate sodium administered to C57BL/6-mice. Depression was induced by intracerebroventricular infusion of reserpine in healthy or vagotomized mice treated with antidepressant desmethylimipramine (DMI). Colitis was assessed macroscopically, histologically, and by C-reactive protein measurement in serum and by cytokines in colonic samples. Cytokine release was measured on macrophages isolated from these models. Naive macrophage colony-stimulating factor-deficient mice (op/op) were injected with peritoneal macrophages obtained from the different groups and acute colitis was induced. Vagotomy reactivated inflammation in mice with chronic colitis. DLB reactivated colitis and this was prevented by DMI only in mice with intact vagi. Macrophages isolated from vagotomized or DLB-mice showed a selective increase of proinflammatory cytokine release and this was not seen in macrophages isolated from DLB-DMI-treated mice; moreover, vagotomy abolished this beneficial effect. In op/op, adoptive transfer of macrophages from non-DLB mice significantly increased the inflammatory markers. These parameters were significantly increased when transferred with macrophages isolated from DLB or VXP mice. Op/op mice that received macrophages from DLB-DMI-treated mice showed a significant decrease of all parameters and vagotomy abolished this effect. These data identify the critical role of macrophage in linking depression and susceptibility to intestinal inflammation via the vagus nerve. The results provide a basis for developing new approaches to the management of UC patients with coexisting depression by rebalancing cytokine production by the cell

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

    PubMed

    Veerappan, Sundaram G; O'Morain, Colm A

    2009-07-01

    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.

  18. A new combination of multiple autoimmune syndrome? Coexistence of vitiligo, autoimmune thyroid disease and ulcerative colitis.

    PubMed

    Topal, Firdevs; Senel, Engin; Akbulut, Sabiye; Topal, Fatih; Dölek, Yasemin

    2011-08-03

    The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto's thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

  19. Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease

    SciTech Connect

    Balestra, D.J.; Balestra, S.T.; Wasson, J.H.

    1988-07-01

    The authors describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitital and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

  20. Ulcerative colitis associated with the herbal weight loss supplement Hydroxycut

    PubMed Central

    Sivarajah, Vernon; Abdul, Quddus; Pardoe, Helen; Lunniss, Peter

    2013-01-01

    A 25-year-old Iranian gentleman was admitted to hospital with severe bloody diarrhoea and abdominal pain. He had similar episodes in the past. On each occasion his symptoms developed following the consumption of the herbal weight loss supplement Hydroxycut Hardcore X. On this admission, a (CT) scan demonstrated bowel wall thickening and peri-colonic fat stranding in the sigmoid colon. On flexible sigmoidoscopy, a continuous length of congested mucosa with multiple small ulcers was seen extending up to the mid-transverse colon, in keeping with ulcerative colitis. Histological analysis of biopsies was taken at the time and confirmed this. He was started on steroids early during his admission but this only provided a transient clinical improvement. The addition of cyclosporine, which was later changed to azathioprine, did not improve his condition either. He therefore underwent an open subtotal colectomy with end ileostomy. He made a slow but steady recovery and was discharged 3 weeks later. PMID:23291814

  1. Biologics for the treatment of pyoderma gangrenosum in ulcerative colitis

    PubMed Central

    Arivarasan, K; Bhardwaj, Vaishali; Sud, Sukrit; Sachdeva, Sanjeev

    2016-01-01

    Pyoderma gangrenosum (PG) is an uncommon extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite limited published literature, biologics have caused a paradigm shift in the management of this difficult-to-treat skin condition. The clinical data and outcomes of three patients with active ulcerative colitis and concurrent PG treated with biologics (infliximab two and adalimumab one) are reviewed in this report. Biologics were added because of the sub-optimal response of the colonic symptoms and skin lesions to parenteral hydrocortisone therapy. All three patients showed a dramatic response to the addition of the biologics. In view of the rapid healing of the skin lesions, superior response rate, and the additional benefit of improvement in the underlying colonic disease following treatment, anti-tumor necrosis factor blockers should be considered as a first line therapy in the management of PG with underlying IBD. PMID:27799888

  2. Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats.

    PubMed

    Liu, Chun-Jie; Jin, Ji-De; Lv, Tong-De; Wu, Zu-Ze; Ha, Xiao-Qin

    2011-06-07

    To investigate the effect of keratinocyte growth factor (KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model. The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5% (v/v) acetic acid. Twenty-four hours after exposed to acetic acid, rats were divided into three experimental groups: control group, attenuated Salmonella typhimurium Ty21a strain (SP) group and SP strain carrying human KGF gene (SPK) group, and they were separately administered orally with 10% NaHCO(3), SP or SPK. Animals were sacrificed and colonic tissues were harvested respectively on day 3, 5, 7 and 10 after administration. Weights of rats, colonic weight/length ratio and stool score were evaluated. Histological changes of colonic tissues were examined by hematoxylin and eosin (HE) staining method. The expression of KGF, KGF receptor (KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting. Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents in the homogenate were measured. Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups (body weight: 272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g, P < 0.01; colonic weight/length ratio: 115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm, P < 0.01). Moreover, pathological changes of damaged colon were improved in SPK group as well. After administration of SPK strain, KGF expression increased markedly from the 3rd d, and remained at a high level till the 10th d. Furthermore, KGFR expression and Ki67 expression elevated, whereas TNF-α expression was inhibited in SPK group. In the group administered with SPK, SOD activity increased significantly (d 5: 26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg, P < 0.01; d 7: 35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg, P < 0.01; d 10

  3. Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

    PubMed Central

    Liu, Chun-Jie; Jin, Ji-De; Lv, Tong-De; Wu, Zu-Ze; Ha, Xiao-Qin

    2011-01-01

    AIM: To investigate the effect of keratinocyte growth factor (KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model. METHODS: The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5% (v/v) acetic acid. Twenty-four hours after exposed to acetic acid, rats were divided into three experimental groups: control group, attenuated Salmonella typhimurium Ty21a strain (SP) group and SP strain carrying human KGF gene (SPK) group, and they were separately administered orally with 10% NaHCO3, SP or SPK. Animals were sacrificed and colonic tissues were harvested respectively on day 3, 5, 7 and 10 after administration. Weights of rats, colonic weight/length ratio and stool score were evaluated. Histological changes of colonic tissues were examined by hematoxylin and eosin (HE) staining method. The expression of KGF, KGF receptor (KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting. Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents in the homogenate were measured. RESULTS: Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups (body weight: 272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g, P < 0.01; colonic weight/length ratio: 115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm, P < 0.01). Moreover, pathological changes of damaged colon were improved in SPK group as well. After administration of SPK strain, KGF expression increased markedly from the 3rd d, and remained at a high level till the 10th d. Furthermore, KGFR expression and Ki67 expression elevated, whereas TNF-α expression was inhibited in SPK group. In the group administered with SPK, SOD activity increased significantly (d 5: 26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg, P < 0.01; d 7: 35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U

  4. Engineered lymphocytes to treat dinitrobenzene sulphonic acid colitis in mice.

    PubMed

    Felley, Christian; Michetti, Pierre

    2003-12-01

    Current treatments of inflammatory bowel diseases are limited either by their lack of efficacy or their potential toxicity. In recent years, major advances have been obtained by the development of biological therapies. However, these types of treatment are systemic and can lead to serious adverse events. The new venue of local biological treatments would be most welcome. In this issue of the Journal, Castagliuolo et al. show that lymphocytes engineered to produce TGF-beta1 can reverse dinitrobenzene sulphonic acid-induced colitis in mice. These engineered lymphocytes selectively accumulate in the intestinal mucosa due to the homing properties of their alpha4beta7 integrins, a ligand for MAdCAM1. A local treatment restricted to the inflamed mucosa can thus be obtained. This opens a brand new area of research with the hope of restoring the immunoregulatory balance selectively in the inflamed tissues.

  5. [Management of severe ulcerative colitis: An up-to-date].

    PubMed

    Hernández-Rocha, Cristian; Ibáñez, Patricio; Molina, María Elena; Klaassen, Julieta; Valenzuela, Andrea; Candia, Roberto; Bellolio, Felipe; Zúñiga, Álvaro; Miguieles, Rodrigo; Miquel, Juan Francisco; Chianale, José; Álvarez-Lobos, Manuel

    2017-01-01

    Ulcerative Colitis (UC) is a chronic inflammatory disease involving the colon, with alternating periods of remission and activity. Exacerbations can be severe and associated with complications and mortality. Diagnosis of severe UC is based on clinical, biochemical and endoscopic variables. Patients with severe UC must be hospitalized. First line therapy is the use of intravenous corticoids which achieve clinical remission in most patients. However, 25% of patients will be refractory to corticoids, situation that should be evaluated at the third day of therapy. In patients without response, cytomegalovirus infection must be quickly ruled out to escalate to second line therapy with biological drugs or cyclosporine. Total colectomy must not be delayed if there is no response to second line therapy, if there is a contraindication for second line therapies or there are complications such as: megacolon, perforation or massive bleeding. An active management with quick escalation on therapy allows to decrease the prolonged exposure to corticoids, reduce colectomy rates and its perioperative complications.

  6. Ulcerative colitis associated with the herbal weight loss supplement Hydroxycut.

    PubMed

    Sivarajah, Vernon; Abdul, Quddus; Pardoe, Helen; Lunniss, Peter

    2013-01-03

    A 25-year-old Iranian gentleman was admitted to hospital with severe bloody diarrhoea and abdominal pain. He had similar episodes in the past. On each occasion his symptoms developed following the consumption of the herbal weight loss supplement Hydroxycut Hardcore X. On this admission, a (CT) scan demonstrated bowel wall thickening and peri-colonic fat stranding in the sigmoid colon. On flexible sigmoidoscopy, a continuous length of congested mucosa with multiple small ulcers was seen extending up to the mid-transverse colon, in keeping with ulcerative colitis. Histological analysis of biopsies was taken at the time and confirmed this. He was started on steroids early during his admission but this only provided a transient clinical improvement. The addition of cyclosporine, which was later changed to azathioprine, did not improve his condition either. He therefore underwent an open subtotal colectomy with end ileostomy. He made a slow but steady recovery and was discharged 3 weeks later.

  7. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease.

    PubMed Central

    Rachmilewitz, D; Stamler, J S; Bachwich, D; Karmeli, F; Ackerman, Z; Podolsky, D K

    1995-01-01

    Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury. PMID:7541008

  8. Looking for the best anti-colitis medicine: A comparative analysis of current and prospective compounds

    PubMed Central

    Chumanevich, Anastasiya A.; Chaparala, Anusha; Witalison, Erin E.; Tashkandi, Hossam; Hofseth, Anne B.; Lane, Corey; Pena, Edsel; Liu, Piaomu; Pittman, Doug L.; Nagarkatti, Prakash; Nagarkatti, Mitzi; Hofseth, Lorne J.; Chumanevich, Alexander A.

    2017-01-01

    Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon, which, while untreated, has a relapsing and remitting course with increasing risk of progression toward colorectal cancer. Current medical treatment strategies of UC mostly focus on inhibition of the signs and symptoms of UC to induce remission and prevent relapse of disease activity, minimizing the impact on quality of life, but not affecting the cause of disease. To date, however, there is no single reliable treatment agent and/or strategy capable of effectively controlling colitis progression throughout the patient's life without side effects, remission, or resistance. Taking into consideration an urgent need for the new colitis treatment strategies, targets and/or modulators of inflammation, we have tested current and prospective compounds for colitis treatment and directly compared their anti-colitis potency using a dextran sulfate sodium (DSS) mouse model of colitis. We have introduced a composite score – a multi-parameters comparison tool – to assess biological potency of different compounds. PMID:27974688

  9. Nerol alleviates pathologic markers in the oxazolone-induced colitis model.

    PubMed

    González-Ramírez, Adriana Estrella; González-Trujano, María Eva; Orozco-Suárez, Sandra A; Alvarado-Vásquez, Noé; López-Muñoz, Francisco Javier

    2016-04-05

    Nerol is a natural monoterpene with antinociceptive and anti-inflammatory properties. Its possible beneficial effects in ulcerative colitis and its corresponding mechanism of action have not been determined to date. The aim of this study was to investigate whether nerol prevents the appearance of pathological markers and hyperalgesia in oxazolone-induced colitis, and protects against gastric damage produced by ethanol. The experimental design included groups of oxazolone-treated mice receiving nerol at 10-300 mg/kg, p.o., or a reference drug (sulfasalazine, 100 mg/kg, p.o.) compared to sham and untreated groups. Gastric damage was evaluated in the absolute ethanol-induced ulcer model in rats. Variables measured in animals with oxazolone-induced colitis included weight loss, stool consistency and macroscopic colon damage; mechanical nociception was determined by the use of von Frey filaments, whereas levels of inflammatory cytokines were assessed by enzyme-linked immunosorbent assay. Nerol (30-300 mg/kg, p.o.) prevented or significantly decreased the pathological alterations observed in the oxazolone- induced colitis model. It also showed antinociceptive effects and reduced the increased levels of inflammatory cytokines (IL-13 and TNF-α). Gastric damage was also prevented starting at 10 mg/kg, p.o. In conclusion, our results provide evidence for a beneficial effect of nerol after colitis induction involving tissue protection, antinociception and modulation of the immunological system, suggesting the therapeutic potential of this monoterpene as a novel alternative in controlling ulcerative colitis.

  10. Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis

    PubMed Central

    Cui, Xiangli; Jin, Yu; Poudyal, Deepak; Chumanevich, Alexander A.; Davis, Tia; Windust, Anthony; Hofseth, Anne; Wu, Wensong; Habiger, Joshua; Pena, Edsel; Wood, Patricia; Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Hofseth, Lorne

    2010-01-01

    We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage. We found there were 82 protein end points that were either significantly higher (41 proteins) or significantly lower (41 proteins) in the AOM + DSS group compared with the AOM-alone (control) group. In contrast, there were only 19 protein end points that were either significantly higher (10 proteins) or significantly lower (9 proteins) in the AOM + DSS + AG group compared with the AOM-alone (control) group. Overall, these results suggest that AG keeps the colon environment in metabolic equilibrium when mice are treated with AOM + DSS and gives insight into the mechanisms by which AG protects from colon cancer associated with colitis. PMID:20729391

  11. Effect of Infliximab and Adalimumab on Experimental Colitis Following Orally Supplemented Iron.

    PubMed

    Triantafillidis, John; Vagianos, Costas; Agrogiannis, George; Gikas, Aristofanis; Douvi, Georgia; Syrmos, Nikolaos; Patsouris, Efstratios; Papalois, Apostolos

    2017-02-01

    Orally administered iron can induce colonic inflammation in healthy animals and aggravate experimental colitis. To investigate the influence of the biologic agents infliximab and adalimumab on the severity of TNBS colitis following orally supplemented iron. 204 Wistar rats were allocated into 14 groups. Colitis was induced by TNBS. Iron was administered via a mouth catheter at a dose of 0.027, 0.3, and 3%/kg diet per day, respectively. Infliximab was subcutaneously administered on the 2(nd) and 6(th) day in a dose of 5 mg/kgBW, while adalimumab was administered on the 2(nd) day in a dose of 2 mg/kgBW. On the 8(th) day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. Tissue Tumor Necrosis Factor-α (t-TNF-α) and malondialdehyde (t-MDA) were estimated. In normal rats both agents significantly worsen the degree of inflammation induced by moderate or high iron supplementation despite the disappearance of t-TNF-α, and reduction of t-MDA. In the groups of TNBS colitis and moderate or high iron administration, both agents again significantly worsen the degree of inflammation despite the significant reduction in the t-TNF-α and t-MDA. Adalimumab and infliximab do not ameliorate the inflammation in TNBS-induced colitis aggravated by orally administered iron. These findings might be clinically relevant in patients with active IBD under concurrent treatment with biologic agents and per oral iron.

  12. PPARα-dependent exacerbation of experimental colitis by the hypolipidemic drug fenofibrate

    PubMed Central

    Qi, Yunpeng; Jiang, Changtao; Tanaka, Naoki; Krausz, Kristopher W.; Brocker, Chad N.; Fang, Zhong-Ze; Bredell, Bryce X.; Shah, Yatrik M.

    2014-01-01

    Fibrates, such as fenofibrate, are peroxisome proliferator-activated receptor-α (PPARα) agonists and have been used for several decades as hypolipidemic agents in the clinic. However, contradictory observations exist on the role of fibrates in host response to acute inflammation, with unclear mechanisms. The role of PPARα in colitis was assessed using fenofibrate and Ppara-null mice. Wild-type or Ppara-null mice were subjected to acute colitis under three distinct protocols, dextran sulfate sodium, trinitrobenzenesulfonic acid, and Salmonella Typhi. Serum and colon lipidomics were analyzed to characterize the metabolic profiles by ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Messenger RNAs of PPARα target genes and genes involved in inflammation were determined by qunatitative PCR analysis. Fenofibrate treatment exacerbated inflammation and tissue injury in acute colitis, and this was dependent on PPARα activation. Lipidomics analysis revealed that bioactive sphingolipids, including sphingomyelins (SM) and ceramides, were significantly increased in the colitis group compared with the control group; this was further potentiated following fenofibrate treatment. In the colon, fenofibrate did not reduce the markedly increased expression of mRNA encoding TNFα found in the acute colitis model, while it decreased hydrolysis and increased synthesis of SM, upregulated RIPK3-dependent necrosis, and elevated mitochondrial fatty acid β-oxidation, which were possibly related to the exacerbated colitis. PMID:25035112

  13. MTG16 is a tumor suppressor in colitis-associated carcinoma

    PubMed Central

    McDonough, Elizabeth M.; Barrett, Caitlyn W.; Parang, Bobak; Mittal, Mukul K.; Smith, J. Joshua; Bradley, Amber M.; Choksi, Yash A.; Coburn, Lori A.; Short, Sarah P.; Zhang, Baolin; Poindexter, Shenika V.; Fischer, Melissa A.; Chen, Xi; Li, Jiang; Revetta, Frank L.; Naik, Rishi; Washington, M. Kay; Rosen, Michael J.; Hiebert, Scott W.; Wilson, Keith T.; Williams, Christopher S.

    2017-01-01

    MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16–/– mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis. MTG16 was downregulated at the protein and RNA levels in patients with inflammatory bowel disease and in those with colitis-associated carcinoma. Mtg16–/– mice subjected to inflammatory carcinogenesis modeling exhibited worse colitis and increased tumor multiplicity and size. Loss of MTG16 also increased severity of dysplasia, apoptosis, proliferation, DNA damage, and WNT signaling. Moreover, transplantation of WT marrow into Mtg16–/– mice failed to rescue the Mtg16–/– protumorigenic phenotypes, indicating an epithelium-specific role for MTG16. While MTG dysfunction is widely appreciated in hematopoietic malignancies, the role of this gene family in epithelial homeostasis, and in colon cancer, was unrealized. This report identifies MTG16 as an important modulator of colitis and tumor development in inflammatory carcinogenesis. PMID:28814670

  14. Early Detection of T cell Transfer-induced Autoimmune Colitis by In Vivo Imaging System

    PubMed Central

    Chen, Yu-Ling; Chen, Yi-Ting; Lo, Cheng-Feng; Hsieh, Ching-I; Chiu, Shang-Yi; Wu, Chang-Yen; Yeh, Yu-Shan; Hung, Shu-Hsuan; Cheng, Po-Hao; Su, Yu-Hsuan; Jiang, Si-Tse; Chin, Hsian-Jean; Su, Yu-Chia

    2016-01-01

    Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn’s disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25−CD45RBhiCD4+ (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has sufficient sensitivity nor totally matches the pathological findings of CD. To establish an early and sensitive indicator of autoimmune colitis model, the transferred T cell-induced colitis mouse model was modified by transferring luciferase-expressing donor T cells and determining the colitis by in vivo imaging system (IVIS). Colitis was detected with IVIS 7–10 days before the onset of body weight loss and diarrhea. IVIS was also applied in the dexamethasone treatment trial, and was a more sensitive indicator than body weight changes. All IVIS signals were parallel to the pathological abnormalities of the gut and immunological analysis results. In summary, IVIS provides both sensitive and objective means to monitor the disease course of transferred T cell-induced CD and fulfills the 3Rs principle of humane care of laboratory animals. PMID:27762297

  15. Early Detection of T cell Transfer-induced Autoimmune Colitis by In Vivo Imaging System.

    PubMed

    Chen, Yu-Ling; Chen, Yi-Ting; Lo, Cheng-Feng; Hsieh, Ching-I; Chiu, Shang-Yi; Wu, Chang-Yen; Yeh, Yu-Shan; Hung, Shu-Hsuan; Cheng, Po-Hao; Su, Yu-Hsuan; Jiang, Si-Tse; Chin, Hsian-Jean; Su, Yu-Chia

    2016-10-20

    Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn's disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25(-)CD45RB(hi)CD4(+) (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has sufficient sensitivity nor totally matches the pathological findings of CD. To establish an early and sensitive indicator of autoimmune colitis model, the transferred T cell-induced colitis mouse model was modified by transferring luciferase-expressing donor T cells and determining the colitis by in vivo imaging system (IVIS). Colitis was detected with IVIS 7-10 days before the onset of body weight loss and diarrhea. IVIS was also applied in the dexamethasone treatment trial, and was a more sensitive indicator than body weight changes. All IVIS signals were parallel to the pathological abnormalities of the gut and immunological analysis results. In summary, IVIS provides both sensitive and objective means to monitor the disease course of transferred T cell-induced CD and fulfills the 3Rs principle of humane care of laboratory animals.

  16. Actions of Probiotics on Trinitrobenzenesulfonic Acid-Induced Colitis in Rats

    PubMed Central

    Shiina, Takahiko; Shima, Takeshi; Naitou, Kiyotada; Nakamori, Hiroyuki; Sano, Yuuki; Horii, Kazuhiro; Shimakawa, Masaki; Ohno, Hiroshi; Shimizu, Yasutake

    2015-01-01

    We investigated the actions of probiotics, Streptococcus faecalis 129 BIO 3B (SF3B), in a trinitrobenzenesulfonic acid- (TNBS-) induced colitis model in rats. After TNBS was administered into the colons of rats for induction of colitis, the rats were divided into two groups: one group was given a control diet and the other group was given a diet containing SF3B for 14 days. There were no apparent differences in body weight, diarrhea period, macroscopic colitis score, and colonic weight/length ratio between the control group and SF3B group, suggesting that induction of colitis was not prevented by SF3B. Next, we investigated whether SF3B-containing diet intake affects the restoration of enteric neurotransmissions being damaged during induction of colitis by TNBS using isolated colonic preparations. Recovery of the nitrergic component was greater in the SF3B group than in the control group. A compensatory appearance of nontachykininergic and noncholinergic excitatory components was less in the SF3B group than in the control group. In conclusion, the present study suggests that SF3B-containing diet intake can partially prevent disruptions of enteric neurotransmissions induced after onset of TNBS-induced colitis, suggesting that SF3B has therapeutic potential. PMID:26550572

  17. Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis.

    PubMed

    Linden, David R; Chen, Jing-Xian; Gershon, Michael D; Sharkey, Keith A; Mawe, Gary M

    2003-07-01

    5-HT released from enterochromaffin cells acts on enteric nerves to initiate motor reflexes. 5-HT's actions are terminated by a serotonin reuptake transporter (SERT). In this study, we tested the hypothesis that inflammation leads to altered mucosal 5-HT signaling. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and experiments were conducted on day 6. 5-HT content, number of 5-HT-immunoreactive cells, and the proportion of epithelial cells that were 5-HT-immunoreactive increased twofold in colitis. The amount of 5-HT released under basal and stimulated conditions was significantly increased in colitis. SERT inhibition increased the 5-HT concentration in media bathing-stimulated control tissue to a level comparable to that of the stimulated colitis tissue. mRNA encoding SERT and SERT immunoreactivity were reduced during inflammation. Slower propulsion and reduced sensitivity to 5-HT-receptor antagonism were observed in colitis. These data suggest that colitis alters 5-HT signaling by increasing 5-HT availability while decreasing 5-HT reuptake. Altered 5-HT availability may contribute to the dysmotility of inflammatory bowel disease, possibly due to desensitization of 5-HT receptors.

  18. Ulcerative colitis and Crohn's disease: is Mycobacterium avium subspecies paratuberculosis the common villain?

    PubMed

    Pierce, Ellen S

    2010-12-17

    Mycobacterium avium, subspecies paratuberculosis (MAP) causes a chronic disease of the intestines in dairy cows and a wide range of other animals, including nonhuman primates, called Johne's ("Yo-knee's") disease. MAP has been consistently identified by a variety of techniques in humans with Crohn's disease. The research investigating the presence of MAP in patients with Crohn's disease has often identified MAP in the "negative" ulcerative colitis controls as well, suggesting that ulcerative colitis is also caused by MAP. Like other infectious diseases, dose, route of infection, age, sex and genes influence whether an individual infected with MAP develops ulcerative colitis or Crohn's disease. The apparently opposite role of smoking, increasing the risk of Crohn's disease while decreasing the risk of ulcerative colitis, is explained by a more careful review of the literature that reveals smoking causes an increase in both diseases but switches the phenotype from ulcerative colitis to Crohn's disease. MAP as the sole etiologic agent of both ulcerative colitis and Crohn's disease explains their common epidemiology, geographic distribution and familial and sporadic clusters, providing a unified hypothesis for the prevention and cure of the no longer "idiopathic" inflammatory bowel diseases.

  19. Dinitrochlorobenzene-induced colitis in the guinea-pig: studies of colonic lamina propria lymphocytes.

    PubMed Central

    Glick, M E; Falchuk, Z M

    1981-01-01

    Dinitrochlorobenzene-induced colitis in guinea-pigs may be immunologically mediated: animals must be presensitised to dinitrochlorobenzene to develop colitis, sensitivity can be passively transferred by lymphocytes and the injury can be mitigated by immunosuppression. In this study, we examined lamina propria lymphocytes isolated from colons of animals with dinitrochlorobenzene-induced colitis, and appropriate controls. Lamina propria lymphocytes from colitis animals have a greater percentage of rabbit erythrocyte-rosetting cells (T cells) (20.1 +/- 3.0 vs 2.3 +/- 0.8, p less than .01) and a greater capacity to mediate mitogen-induced cellular cytotoxicity with phytohaemagglutinin than lamina propria lymphocytes from normal colon (% specific cytoxicity = 29.4 +/- 8.7 vs 5.0 +/- 4.5, P less than .005). There was no difference in the percentage of rosetting cells or cytotoxicity index of spleen or mesenteric lymph node lymphocytes between the colitis animals and controls. These data suggest that there are changes in the distribution and functional characteristics of lamina propria lymphocytes which correlate with mucosal cell injury in the dinitrochlorobenzene-colitis model. Images Figure PMID:6971239

  20. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice

    PubMed Central

    Rui, Ke; Tian, Xinyu; Ma, Jie; Ma, Bin; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-01-01

    Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4+ T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro. Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion. PMID:26885611

  1. Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis.

    PubMed

    Figliuolo, Vanessa Ribeiro; Dos Santos, Liliane Martins; Abalo, Alessandra; Nanini, Hayandra; Santos, Angela; Brittes, Nilda M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira; Vieira, Leda Quercia; Coutinho-Silva, Robson; Coutinho, Claudia Mara Lara Melo

    2017-11-15

    The intestinal microbiota is critical for mammalian immune system development and homeostasis. Sulfate-reducing bacteria (SRB) are part of the normal gut microbiota, but their increased levels may contribute to colitis development, likely in association with hydrogen sulfide (H2S) production. Here, we investigated the effects of SRB in the gut immune response in germ-free mice, and in experimental colitis. After 7days of colonization with Desulfovibrio indonesiensis or with a human SRB consortium (from patients with colitis), germ-free mice exhibited alterations in the colonic architecture, with increased cell infiltration in the lamina propria. SRB colonization upregulated the Th17 and Treg profiles of cytokine production/cell activation, in T cells from mesenteric lymph nodes. These alterations were more pronounced in mice colonized with the human SRB consortium, although D. indonesiensis colonization produced higher levels of H2S. Importantly, the colon of C57BL/6 mice with colitis induced by TNBS or oxazolone had increased SRB colonization, and the administration of D. indonesiensis to mice with TNBS-induced colitis clearly exacerbated the alterations in colonic architecture observed in the established disease, and also increased mouse weight loss. We conclude that SRB contribute to immune response activation in the gut and play an important role in colitis development. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism

    PubMed Central

    Eken, A; Singh, AK; Treuting, PM; Oukka, M

    2013-01-01

    Polymorphisms of interleukin (IL)-23R and signaling components are associated with several autoimmune diseases, including inflammatory bowel diseases (IBD). Similar to T helper type 17 (Th17) lineage, type 3 innate lymphoid cells (ILCs) express retinoic acid–related orphan receptor γt (Rorγt) and IL-23R and hence, produce Th17-type cytokines. Recent reports implicated type 3 ILCs in IBD; however, how IL-23R signaling in these cells contributes to pathogenesis is unknown. IL-22, produced in copious amounts by type 3 ILCs, was reported to have both beneficial and pathogenic effects in adaptive, yet only a protective role in innate colitis models. Herein, by employing chronic CD45RBhigh CD4+ T-cell transfer and anti-CD40 antibody-induced acute innate colitis models in Rag1−/− mice, wedemonstrated opposite roles for IL-23R in colitogenesis: in the former a protective, and in the latter a pathogenic role. Furthermore, we show that IL-23R signaling promotes innate colitis via IL-22 as neutralization of IL-22 protected mice from colitis and adding back of IL-22 to IL-23R-deficient animals restored the disease. Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner. PMID:23715173

  3. Potential role for ET-2 acting through ETA receptors in experimental colitis in mice.

    PubMed

    Claudino, R F; Leite, D F; Bento, A F; Chichorro, J G; Calixto, J B; Rae, G A

    2017-02-01

    This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis. Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors. Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1β, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ETA and ETB receptors mRNA were increased at 24, 48 and 72 h after colitis induction. Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ETA receptors might be a potential target for inflammatory bowel diseases.

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

    PubMed

    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.

  5. Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.

    PubMed

    Fu, Jianxin; Wei, Bo; Wen, Tao; Johansson, Malin E V; Liu, Xiaowei; Bradford, Emily; Thomsson, Kristina A; McGee, Samuel; Mansour, Lilah; Tong, Maomeng; McDaniel, J Michael; Sferra, Thomas J; Turner, Jerrold R; Chen, Hong; Hansson, Gunnar C; Braun, Jonathan; Xia, Lijun

    2011-04-01

    Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell-specific deficiency of core 1-derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1-derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1-derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.

  6. Suppressive effect of berberine on experimental dextran sulfate sodium-induced colitis.

    PubMed

    Hong, Tie; Yang, Zhen; Lv, Chuan-Feng; Zhang, Yu

    2012-06-01

    The anti-inflammatory effect of berberine was evaluated in murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Berberine, given orally at 40, 20, 10 mg/kg for 10 days, ameliorated all the supposed inflammatory symptoms of the induced colitis, such as body weightloss, blood hemoglobin reduction, high myeloperoxidase levels, and malondialdehyde content-inflamed mucosa. Furthermore, the cytokine production of splenic lymphocytes was analyzed. The results showed the IFN-γ and IL-12 were increased, but IL-4 and IL-10 were decreased in DSS-induced colitis,when those were compared with the normal control. But the administration of berberine to DSS-induced colitis mice showed lower production of IFN-γ and IL-12 and higher production of IL-4 and IL-10 than the DSS-induced colitis mice. The results suggest that the protective effects of berberine against the DSS-induced colitis may be associated with the regulation of cytokine production.

  7. Glucose intolerance and diabetes mellitus in ulcerative colitis: Pathogenetic and therapeutic implications

    PubMed Central

    Maconi, Giovanni; Furfaro, Federica; Sciurti, Roberta; Bezzio, Cristina; Ardizzone, Sandro; de Franchis, Roberto

    2014-01-01

    Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients. The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification. Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications, with potential clinical impact on the follow up and outcome of patients. These diseases share specific complications, such as neuropathy, hepatic steatosis, osteoporosis and venous thrombosis. It is still unknown whether the coexistence of these diseases may increase their occurrence. Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis. Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging. Corticosteroids are the treatment of choice of active ulcerative colitis. Their use may be associated with the onset of glucose intolerance and diabetes, with difficult control of glucose levels and with complications in diabetic patients. Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review. PMID:24707133

  8. Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis

    PubMed Central

    Keely, Simon; Campbell, Eric L.; Baird, Alan W.; Hansbro, Philip M.; Shalwitz, Robert A.; Kotsakis, Anna; McNamee, Eoin N.; Eltzschig, Holger K.; Kominsky, Douglas J.; Colgan, Sean P.

    2013-01-01

    Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by TNBS were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi and clinical, immunological and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared to vehicle controls. Treated groups were pyrexic, but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of IL-1β, IL-6 and TNF-α, while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1α deficient mice, strongly implicating epithelial HIF-1α as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis. PMID:23695513

  9. Glucose intolerance and diabetes mellitus in ulcerative colitis: pathogenetic and therapeutic implications.

    PubMed

    Maconi, Giovanni; Furfaro, Federica; Sciurti, Roberta; Bezzio, Cristina; Ardizzone, Sandro; de Franchis, Roberto

    2014-04-07

    Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients. The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification. Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications, with potential clinical impact on the follow up and outcome of patients. These diseases share specific complications, such as neuropathy, hepatic steatosis, osteoporosis and venous thrombosis. It is still unknown whether the coexistence of these diseases may increase their occurrence. Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis. Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging. Corticosteroids are the treatment of choice of active ulcerative colitis. Their use may be associated with the onset of glucose intolerance and diabetes, with difficult control of glucose levels and with complications in diabetic patients. Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review.

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

    PubMed

    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".

  11. Zinc sulphate solution enema decreases inflammation in experimental colitis in rats.

    PubMed

    Chen, B W; Wang, H H; Liu, J X; Liu, X G

    1999-11-01

    It has been reported that zinc sulphate contributes an anti-inflammatory action in many animal models; however, the impact of zinc in colitis remains unclear. The aim of the present study was to examine the role of zinc sulphate in experimental colitis. Colitis was induced by 2,4,6-trinitrobenzenesulphonic acid (TNB) in rats. Beginning at the first day of TNB colitis, the rats were treated with a zinc sulphate enema once daily for 6 days. The rats were examined 8 days later. The TNB induced severe colitis as evidenced by increased mucosal lesion area, mucosal myeloperoxidase (MPO) activity and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Six days after the application of the zinc sulphate enema, the mucosal lesion area, MPO activity, PGE2 and LTB4 levels all decreased significantly. Mucosal superoxide dismutase activity remained unchanged after zinc treatments. Our data suggest that zinc sulphate enemas have an anti-inflammatory action on experimental colitis.

  12. Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis.

    PubMed Central

    Kawahito, Y; Sano, H; Mukai, S; Asai, K; Kimura, S; Yamamura, Y; Kato, H; Chrousos, G P; Wilder, R L; Kondo, M

    1995-01-01

    Corticotropin releasing hormone (CRH) is a key hormone in integrated response to stress, acting as the major regulator of the hypothalamic-pituitary-adrenal axis. Recently, local production of CRH has been detected in normal human colonic enterochromaffin cells. CRH is locally secreted in granulomatous and arthritic tissues in rats and humans, where it seems to act as a local proinflammatory agent. To find out if CRH is present in colonic tissues of patients with ulcerative colitis, this study examined the expression of this peptide in the large bowel of patients with ulcerative colitis. Colonic tissues of patients with ulcerative colitis obtained by endoscopic biopsy were immunostained with anti-CRH antibody. CRH messenger (m) RNA was also examined in biopsy specimens of ulcerative colitis by the reverse transcribed polymerase chain reaction method and by in situ hybridisation. Considerably enhanced expression of immunoreactive CRH was found in mucosal inflammatory cells. Intense staining with anti-CRH antibody was also shown in mucosal macrophages. CRH mRNA was expressed in mucosal epithelial cells. The expression of immunoreactive CRH in colonic mucosal epithelial cells of ulcerative colitis slightly increased, but not significantly, compared with normal colonic mucosal epithelial cells. These results suggest that CRH may play a part in the modulation of intestinal immune and inflammatory system, and as a modulator in the pathogenesis of ulcerative colitis. Images Figure 1 Figure 2 Figure 4A Figure 4B-4C Figure 5 PMID:7489943

  13. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism.

    PubMed

    Eken, A; Singh, A K; Treuting, P M; Oukka, M

    2014-01-01

    Polymorphisms of interleukin (IL)-23R and signaling components are associated with several autoimmune diseases, including inflammatory bowel diseases (IBD). Similar to T helper type 17 (Th17) lineage, type 3 innate lymphoid cells (ILCs) express retinoic acid-related orphan receptor γt (Rorγt) and IL-23R and hence, produce Th17-type cytokines. Recent reports implicated type 3 ILCs in IBD; however, how IL-23R signaling in these cells contributes to pathogenesis is unknown. IL-22, produced in copious amounts by type 3 ILCs, was reported to have both beneficial and pathogenic effects in adaptive, yet only a protective role in innate colitis models. Herein, by employing chronic CD45RB(high) CD4(+) T-cell transfer and anti-CD40 antibody-induced acute innate colitis models in Rag1(-/-) mice, we demonstrated opposite roles for IL-23R in colitogenesis: in the former a protective, and in the latter a pathogenic role. Furthermore, we show that IL-23R signaling promotes innate colitis via IL-22 as neutralization of IL-22 protected mice from colitis and adding back of IL-22 to IL-23R-deficient animals restored the disease. Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner.

  14. The effect of methylsulfonylmethane on the experimental colitis in the rat

    SciTech Connect

    Amirshahrokhi, K.; Bohlooli, S.; Chinifroush, M.M.

    2011-06-15

    Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects. MSM is an organosulfur compound and a normal oxidative metabolite of dimethyl sulfoxide. This study was carried out to investigate the effect of MSM in a rat model of experimental colitis. Colitis was induced by intracolonic instillation of 1 ml of 5% of acetic acid. Rats were treated with MSM (400 mg/kg/day, orally) for 4 days. Animals were euthanized and distal colon evaluated histologically and biochemically. Tissue samples were used to measurement of malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH) and proinflammatory cytokine (TNF-{alpha} and IL-1{beta}) levels. Results showed that MSM decreased macroscopic and microscopic colonic damage scores caused by administration of acetic acid. MSM treatment also significantly reduced colonic levels of MDA, MPO and IL-1{beta}, while increased the levels of GSH and CAT compared with acetic acid-induced colitis group. It seems that MSM as a natural product may have a protective effect in an experimental ulcerative colitis. - Research Highlights: > Methylsulfonylmethane occurs naturally in some green plants, fruits and vegetables. > Methylsulfonylmethane (MSM) has anti-inflammatory and antioxidant effects. > We evaluated the effects of MSM in a rat model of experimental ulcerative colitis. > MSM has protective effect against acetic acid-induced colitis in rat.

  15. An Inducible, Large-Intestine-Specific Transgenic Mouse Model for Colitis and Colitis-Induced Colon Cancer Research.

    PubMed

    Wang, Fa; Johnson, Robert L; Snyder, Paul W; DeSmet, Marsha L; Fleet, James C

    2016-04-01

    Animal models are an important tool to understand intestinal biology. Our laboratory previously generated C57BL/6-Tg(Car1-cre)5Flt transgenic mice (CAC) with large-intestine-specific Cre recombinase (Cre) expression as a model to study colon health. To expand the utility of the CAC mouse model by determining the impact of chemically induced colitis on CAC transgene expression. CAC mice were crossed to Rosa reporter mice (Rosa26R (flox/flox) ) with a lox-STOP-lox signal controlling β-galactosidase (βgal) expression and then further crossed with Apc(CKO/CKO) mice in some experiments to delete Apc alleles (Apc (Δ580) ). Initially, 8-week-old CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice were treated with dextran sulfate sodium (DSS) in drinking water (5 days, 0, 0.65, 1.35, or 2.0 %). Colon tissue damage and βgal labeling were analyzed 10 day after stopping DSS. Next, 8-week-old CAC(Tg/WT);Rosa26R(flox/flox) mice were treated with 0 or 1.35 % DSS, and colonic βgal labeling was assessed at 30 day post-DSS treatment. Finally, 10-week-old CAC(Tg/WT);Apc (Δ580/WT) mice were treated with DSS (0 or 2 %) for 5 days and colonic tumors were analyzed at 20 weeks. CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice had a DSS dose-dependent increase in colon epithelial damage that correlated with increased epithelial βgal labeling at 10 days (r (2) = 0.9, β = 0.75). The βgal labeling in CAC(Tg/WT);Rosa26R(flox/flox) mice colon remained high at 30 days, especially in the crypts of the healed ulcer. DSS also increased colon tumor incidence and multiplicity in CAC(Tg/WT);Apc (Δ580/WT) mice. DSS-mediated epithelial damage induces a persistent, Cre-mediated recombination of floxed alleles in CAC mice. This enables the examination of gene function in colon epithelium during experimental colitis and colitis-induced colon cancer.

  16. Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis.

    PubMed

    Rachmilewitz, Daniel; Karmeli, Fanny; Shteingart, Shimon; Lee, Jongdae; Takabayashi, Kenji; Raz, Eyal

    2006-05-01

    We previously showed that Toll-like receptor-9 (TLR-9) ligands ameliorate experimental colitis. In this study, we evaluated the effect of TLR-9 ligands on the generation of proinflammatory cytokines by human colonic mucosa. Colonoscopic biopsies were obtained from patients with active ulcerative colitis (UC) and from normal subjects. The tissue was organ cultured for 24 hours in the presence or absence of different types of immunostimulatory (ISS) (CpG)-oligonucleotides (ODNs). Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the medium were determined by enzyme-linked immunosorbent assay. In active UC, hTNF-alpha and hIL-lbeta generation by inflamed colonic mucosa is 7- and 3-fold higher, respectively, than their generation by normal mucosa. Class B CpG ODNs inhibited colonic TNF-alpha and IL-1beta generation by 50%, whereas class A or C ODNs had a partial or no effect, respectively. A novel class of ODNs that is based on multiple TCG repeats was as effective as class B ODNs. This inhibition resulted from the transcriptional suppression of IL-1beta that occurred within the first 2 hours after ISS-ODN incubation. The addition of chloroquine abolished the inhibitory effects of ISS-ODNs on colonic TNF-alpha and IL-1beta generation. Only certain classes of ISS-ODNs inhibit the enhanced TNF-alpha and IL-1beta generated ex vivo by inflamed colonic mucosa of patients with UC. The effect of ISS-ODNs is mediated by triggering of TLR-9. These results suggest a potential therapeutic value for ISS-ODNs in UC.

  17. Management of Mild-to-Moderate Ulcerative Colitis.

    PubMed

    Siegmund, Britta

    2015-09-14

    Managing mild-to-moderate ulcerative colitis on the first view appears to be a simple task. However, real life often proofs the opposite and creates a challenging situation. In theory, mild-to-moderate disease should be sufficiently treated by mesalamine or alternatively by a probiotic. Insufficient treatment comprises the danger of leading to a flare, and hence, an exacerbation of the entire disease, with risk of progressing to severe disease. What are the considerations with regard to patient management in this situation? Certainly, disease distribution is the critical information, since it allows for planning the optimal route of administration, namely local versus systemic treatment. Novel pharmacological strategies might allow for reaching high local concentrations even at the left side of the colon or alternatively administer locally active budesonide throughout the entire colon frame, thus avoiding systemic side effects. Therapy planning has to involve the patient to identify how this can be included in daily life. Including the patient implies that depending on the condition, disease activity and even life quality, the individual therapy requires timely adaption. A recent study by Pedersen et al. [Inflamm Bowel Dis 2014;20:2276-2285] provides evidence that this strategy can be followed and leads to an overall better outcome. A last thought, besides the patient not taking the appropriate dose or lacking adherence to therapy, should consider that a worsening of disease could be due to infectious complications including Clostridium difficile or cytomegalovirus colitis. If all considerations fail within a reasonable time frame, therapy should be escalated. Patients in this situation often hesitate in accepting the need of immunosuppression. Future options, potentially including phosphatidylcholine, might bridge the gap between mesalamine, probiotics and immunosuppressive strategies. © 2015 S. Karger AG, Basel.

  18. Fulminant amoebic colitis: a clinicopathological study of 30 cases.

    PubMed

    Chaturvedi, Rachana; Gupte, Prajakta A; Joshi, Amita S

    2015-04-01

    To review the clinical and pathological factors associated with fulminant amoebic colitis (FAC) requiring colonic resection and its outcome. We retrospectively identified adult patients admitted to our centre between June 2007 and December 2011 with FAC who underwent colonic resection and were diagnosed with amoebic colitis based on the presence of trophozoites on histological examination. The clinical details were extracted from the medical notes and correlated with the pathological findings. Thirty patients (18 men and 12 women) met the inclusion criteria. Their mean age was 50.1 years (range 21-89). The most frequent symptoms were abdominal pain, vomiting and fever. More than half the patients (16/30) had underlying conditions associated with immunosuppression including diabetes mellitus and tuberculosis. Pathological investigation of colonic resections showed predominantly right-sided involvement with geographic colonic ulcers covered with a creamy-white pseudomembrane, perforations, gangrenous changes, amoeboma and lesions mimicking inflammatory bowel disease. All showed basophilic dirty necrosis with abundant nuclear debris and amoebic trophozoites on histological examination. 21/30 patients (70%) had involvement beyond the caecum. 17/30 patients (57%) died. Those with involvement beyond the caecum were more likely to die (15/21, 71.4%) than those with less extensive disease. FAC presents as acute abdomen and can mimic appendicitis, ischaemic bowel disease, tuberculosis and malignancy. Comorbidities causing immunosuppression frequently associated. Mortality remains high despite surgery, so FAC should be suspected in every case of acute abdomen with colonic perforation if associated with typical gross and microscopic findings and a history of stay in an endemic area. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Effects of garlicin on apoptosis in rat model of colitis

    PubMed Central

    Xu, Xi-Ming; Yu, Jie-Ping; He, Xiao-Fei; Li, Jun-Hua; Yu, Liang-Liang; Yu, Hong-Gang

    2005-01-01

    AIM: To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC). METHODS: Healthy adult Sprague-Dawley rats of both sexes, weighing 180±30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitr-obenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated. RESULTS: In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The positive expression of bax in lymphocytes had no significant difference. CONCLUSION: Garlicin can protect colonic mucosa against damage in rat model of UC induced by TNBS enema. PMID:16052692

  20. Effects of garlicin on apoptosis in rat model of colitis.

    PubMed

    Xu, Xi-Ming; Yu, Jie-Ping; He, Xiao-Fei; Li, Jun-Hua; Yu, Liang-Liang; Yu, Hong-Gang

    2005-08-07

    To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC). Healthy adult Sprague-Dawley rats of both sexes, weighing 180+/-30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated. In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The positiv