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Sample records for colitis collagenous colitis

  1. Complications of collagenous colitis.

    PubMed

    Freeman, Hugh-James

    2008-03-21

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease. PMID:18350593

  2. Collagenous gastroduodenitis on collagenous colitis.

    PubMed

    Stolte, M; Ritter, M; Borchard, F; Koch-Scherrer, G

    1990-07-01

    We report on a case of collagenous gastroduodenitis with concomitant collagenous colitis in a 75-year-old woman with watery diarrhea of approximately six months' standing. The step biopsy material obtained from the colon revealed continuous collagenous colitis with thickening of the basal membrane to 30 microns. The biopsies taken from the stomach and duodenum also revealed a band-like deposition of collagen in the duodenum (bulb and proximal portion of the descending portion) along the basal membrane of the lining epithelium, associated with partial atrophy of the villi. In the stomach, this band of collagen was located, parallel to the mucosal surface, at the level of the floor of the foveolae. PMID:2209504

  3. Lymphocytic and Collagenous Colitis.

    PubMed

    Cruz-Correa; Giardiello

    2000-06-01

    Patients with symptomatic collagenous-lymphocytic colitis should eliminate dietary secretagogues such as caffeine- or lactose-containing food from their diet. When possible, use of nonsteroidal anti-inflammatory drugs should be discontinued. If steatorrhea is documented, a low-fat diet may be helpful. In the presence of bile salt malabsorption, binding resins such as cholestyramine might be useful. Nonspecific diarrheal agents such as loperamide hydrochloride, diphenoxylate hydrochloride and atropine, deodorized tincture of opium, or codeine might prove effective in some patients. Antibacterial agents such as bismuth subsalicylate (8 chewable 262-mg tablets daily) have been effective in symptom control. Metronidazole and erythromycin achieve response rates of 60%. Sulfasalazine, at the usual dose of 2 to 4 g daily, used in collagenous-lymphocytic colitis, demonstrated cessation of diarrhea in 1 to 2 weeks for 50% of patients. Other 5-aminosalicylic (5-ASA) compounds are preferred for patients with a history of sulfa allergy, and those who experience adverse reactions to sulfasalazine. Adrenocorticoid medication is reserved for patients whose conventional treatment with sulfasalazine or 5-ASA has failed. Resolution of diarrhea has been documented in 80% to 90% of patients within 1 week of treatment, however, in most patients, long-term therapy is required. Surgical management is reserved for those patients with disease refractory to medical therapy. Colectomy with ileostomy resulted in clinical and histologic resolution in small case series. If there is no abatement of symptoms, rule out other etiologies of diarrhea such as thyroid dysfunction, celiac disease, or bacterial overgrowth. PMID:11097741

  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. Collagenous gastritis associated with lymphocytic colitis.

    PubMed

    Groisman, G M; Meyers, S; Harpaz, N

    1996-03-01

    Collagenous sprue and collagenous colitis are two well-recognized idiopathic enteritides whose defining histologic attribute is fibrous thickening of the subepithelial basement membrane. Analogous changes in gastric mucosa seem to be quite rare. The term "collagenous gastritis" was recently applied for the first time to an isolated case of refractory gastritis in which distinctive subepithelial gastric fibrosis was noted. We report an additional case of this entity in a 35-year-old woman with refractory dyspepsia. In contrast to the earlier case of collagenous gastritis, our patient also had lymphocytic colitis, a type of colitis associated with watery diarrhea. Collagenous gastritis appears to be a distinct clinicopathologic entity, the histologic changes of which should be sought in patients with unexplained dyspepsia. Increased awareness of this condition and its possible clinical correlates may provide clues to its etiology and pathogenesis. PMID:8742654

  6. Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

    PubMed

    De Petris, Giovanni; Chen, Longwen

    2015-05-01

    Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.

  7. Microscopic Colitis (Lymphocytic and Collagenous), Eosinophilic Colitis, and Celiac Disease

    PubMed Central

    Villanueva, M. Sophia; Alimi, Yewande

    2015-01-01

    Multiple tests are needed to diagnose a patient with noninfectious diarrhea. Some patients will be mistakenly labeled as diarrhea-predominant irritable bowel syndrome (IBS-D) because of nonspecific computed tomographic scans and grossly normal endoscopic findings. It is crucial to understand other less common pathologies to avoid these instances of misdiagnosis. This article focuses on microscopic colitis (MC), eosinophilic colitis (EC), and celiac disease. MC is an inflammatory condition of the colon that presents with two subtypes, only to be differentiated by histology. EC is a rare chronic inflammatory process. Depending on the extent of the disease, it can present with mild diarrhea, malabsorption, or at its worst, cause obstruction and perforation. Celiac disease affects the small bowel, but interestingly can present similarly to colitis. Both MC and EC respond to oral budesonide. Patients with celiac disease improve on gluten-free diets. These treatments are distinctly different from typical IBS-D care plans. PMID:26034409

  8. [Simultaneous occurrence of lymphocytic gastritis and lymphocytic colitis with transition to collagenous colitis].

    PubMed

    Christ, A D; Meier, R; Bauerfeind, P; Wegmann, W; Gyr, K

    1993-07-31

    Lymphocytic gastritis and lymphocytic colitis are two rare disorders of unknown etiology, only diagnosable by histology. Simultaneous occurrence of lymphocytic colitis and lymphocytic gastritis has not been described up to now. A 69-year-old female patient was examined because of crampy abdominal pain and watery diarrhea. Laboratory tests did not reveal an etiology and in colonoscopy the colon and terminal ileum were normal. Histology disclosed lymphocytic colitis. Esophagogastroduodenoscopy showed erosive bulbitis. Biopsies of the stomach revealed lymphocytic gastritis. A second colonoscopy one year later showed the development of collagenous colitis. PMID:8367708

  9. Association of collagenous colitis with prurigo nodularis.

    PubMed

    Székely, Hajnal; Pónyai, Györgyi; Temesvári, Erzsébet; Berczi, Lajos; Hársing, Judit; Kárpáti, Sarolta; Herszényi, László; Tulassay, Zsolt; Juhász, Márk

    2009-08-01

    The etiology and pathogenesis of collagenous colitis (CC) is poorly understood and probably multifactorial; many potential pathophysiological mechanisms have been described, although none have been conclusively proved. Circumstantial evidence suggests that CC appears as an autoimmune response to a luminal or epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID, lansoprazole) may act as triggers for an immune-mediated process. CC is characterized clinically by chronic watery, nonbloody diarrhea with normal endoscopic appearance and without radiological abnormalities, but specific microscopic changes in the colon. Histopathology is featured by the presence of a thickened subepithelial collagen band adjacent to the basal membrane. Up to 40% of patients with CC have associated diseases of autoimmune or inflammatory origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes mellitus, Sjögren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus. We report a case of CC and prurigo nodularis. To our knowledge, this association has not been reported earlier. PMID:19398916

  10. Optimal management of collagenous colitis: a review

    PubMed Central

    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. PMID:26929656

  11. Pseudomembranous colitis

    MedlinePlus

    Antibiotic-associated colitis; Colitis - pseudomembranous; Necrotizing colitis; C difficile - pseudomembranous ... The C difficile bacteria normally lives in the intestine. However, too much of these bacteria may grow when you ...

  12. Pseudomembranous collagenous colitis: an unusual cause of chronic diarrhoea.

    PubMed

    Khan-Kheil, Ayisha Mehtab; Disney, Benjamin; Ruban, Ernie; Wood, Gordon

    2014-02-13

    An 81-year-old woman presented with a history of severe chronic diarrhoea resulting in an admission with syncope and electrolyte abnormalities. Imaging studies of the bowel were normal. However, biopsies taken during colonoscopy enabled a diagnosis to be made and effective treatment to be initiated. This case report details the presentation, diagnosis and management of a rare injury pattern affecting the bowel: pseudomembranous collagenous colitis.

  13. Pseudomembranous collagenous colitis: an unusual cause of chronic diarrhoea

    PubMed Central

    Khan-Kheil, Ayisha Mehtab; Disney, Benjamin; Ruban, Ernie; Wood, Gordon

    2014-01-01

    An 81-year-old woman presented with a history of severe chronic diarrhoea resulting in an admission with syncope and electrolyte abnormalities. Imaging studies of the bowel were normal. However, biopsies taken during colonoscopy enabled a diagnosis to be made and effective treatment to be initiated. This case report details the presentation, diagnosis and management of a rare injury pattern affecting the bowel: pseudomembranous collagenous colitis. PMID:24526204

  14. A COLLAGENOUS COLITIS-LIKE CONDITION IN IMMUNOSUPPRESSED INFANT BABOONS

    PubMed Central

    Dons, Eefje M.; Echeverri, Gabriel J.; Rigatti, Lora H.; Klein, Edwin; Montoya, Claudia; Wolf, Roman F.; Ijzermans, Jan N.M.; Cooper, David K.C.; Wagner, Robert

    2011-01-01

    Background Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. Case Reports We report four infant baboons (age 7–12 months) that had received a transplant at three months of age and subsequent immunosuppressive therapy for periods of 4–10 months. All presented identical symptoms within a period of four weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). Conclusions Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that (i) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; (ii) it was associated with the immunocompromised state of the baboons, as two non-immunosuppressed age-matched baboons in close proximity did not develop the condition, and (iii) it may have had an infectious origin as all four cases developed within a four week period of time. PMID:22294413

  15. 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

  16. Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings.

    PubMed

    Pulimood, A B; Ramakrishna, B S; Mathan, M M

    1999-06-01

    The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts. PMID:10323893

  17. Collagenous gastrobulbitis and collagenous colitis. Case report and review of the literature.

    PubMed

    Castellano, V M; Muñoz, M T; Colina, F; Nevado, M; Casis, B; Solís-Herruzo, J A

    1999-06-01

    A case is reported of collagenous gastrobulbitis on collagenous colitis in a 57-year-old woman with a 6-month history of watery diarrhea. Low serum levels of total proteins and albumin and increased fecal elimination of alpha1-antitrypsin were the only abnormal laboratory test results. Biopsy specimens from the colon, rectum, antrum, fundus, and duodenal bulb showed a thick subepithelial band composed of ultrastructurally normal collagen immunohistochemically negative for collagen IV and laminin. The diarrhea resolved with prednisone and responded to this treatment after a relapse 6 months later. One year later the patient developed severe alimentary intolerance and secondary weight loss. This symptom also responded to the same treatment. However, the collagen deposition did not disappear in the second biopsy samples of colonic and gastric mucosa. Only six cases have been previously reported with gastric and/or duodenal subepithelial collagenous deposition. Four were associated with collagenous colitis. One of these presented a subepithelial collagenous band in the terminal ileum. All these features suggest that this collagen deposition may affect the entire digestive tract with variable intensity, extension, and symptoms. PMID:10440616

  18. 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

  19. Ulcerative colitis - discharge

    MedlinePlus

    Inflammatory bowel disease - ulcerative colitis - discharge; Ulcerative proctitis - discharge; Colitis - discharge ... were in the hospital because you have ulcerative colitis. This is a swelling of the inner lining ...

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

    PubMed

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

    2012-01-01

    We report a case of a 75-year-old woman with urgent watery diarrhea, occurring 5 to 8 times per day, which began after starting lansoprazole (30 mg/day) for erosive gastritis. Her chronic watery diarrhea persisted for over 2 years with mild weight loss. Colonoscopy was performed and biopsies showed collagenous colitis in her transverse colon. We therefore replaced lansoprazole with famotidine (20 mg/day). Within 3 days after the discontinuation of lansoprazole, her watery diarrhea resolved and she recovered, and reported normal feces. Increasing age and female gender are major risk factors for collagenous colitis. The differential diagnosis of collagenous colitis should include: 1) an appropriate clinical history, excluding other etiologies, 2) normal or near-normal endoscopic and/or radiographic findings, and 3) colonoscopic biopsy histopathologic findings consistent with collagenous colitis. The histopathologic findings of colonoscopic biopsy are important for diagnosis. However, because of the colonoscopic burden in elderly patients, we first recommend the discontinuation of medications suspected to cause collagenous colitis. PMID:23459656

  1. 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. PMID:22103057

  2. Ulcerative Colitis

    MedlinePlus

    Ulcerative colitis (UC) is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. ... a group of diseases called inflammatory bowel disease. UC can happen at any age, but it usually ...

  3. Ulcerative colitis

    MedlinePlus

    ... is not clear if immune problems cause this illness. Stress and certain foods can trigger symptoms, but they ... Social support can often help with the stress of dealing with illness, and ... and coping with the condition. The Crohn's and Colitis ...

  4. [Collagenous colitis, IgA deficiency, Basedow's disease and atrophic gastritis].

    PubMed

    Pariente, E A; Chaumette, M T; Maître, F; Delchier, J C; Soulé, J C; Bader, J P

    1985-10-01

    In a 37-year-old woman with chronic watery diarrhea of three years duration, the diagnostic of collagenous colitis was established by optical and ultrastructural examination of rectal and colonic biopsies. No other cause of diarrhea could be found. Moreover, this patient had also selective IgA deficiency, Grave's disease and chronic atrophic gastritis of auto-immune type. Sequential treatments with loperamide, cholestyramine and antibiotics did not modified diarrhea which improved with salazosulfapyridine and betamethasone enemas. These observations suggest that collagenous colitis might be a part of the spectrum of enteropathies associated with immunoglobulin deficiencies. PMID:3840757

  5. Experimental colitis.

    PubMed

    MacPherson, B; Pfeiffer, C J

    1976-01-01

    Ulcerative colitis and Crohn's disease are complex, problematic diseases of unknown etiology in man, and appropriate experimental models would be useful in elucidating their pathogenesis and treatment. Although there have been numerous attempts to produce inflammatory ulcerative colonic disease in laboratory animals resembling those human disease forms, none has been entirely successful. Investigators have conducted experiments involving almost every etiological factor suggested for initiation of these diseases. The methods reviewed in this paper include production of experimental colitis by vascular impairment, and immunological methods such as bacterial infection, allergic reactions, direct and indirect hypersensitivity reactions, as well as autoimmune mechanisms. The results of carrageenan-induced colitis, irradiation, dietary, and drug-induced techniques are also discussed and the frequency and nature of spontaneous colonic lesions in animals is summarized.

  6. [Collagenous gastritis and ileo-colitis occurred in autoimmune context: report of a case and review of the literature].

    PubMed

    Macaigne, Gilles; Boivin, Jean-François; Harnois, Florence; Chayette, Claude; Dikov, Dorian; Cheaib, Sadek; Auriault, Marie-Luce

    2010-09-01

    Collagenous colitis belongs to the group of microscopic colitis. The aetiology and pathogenesis are unknown but different pathogenic hypothesis, autoimmune, infectious, alimentary and medicinal being are advanced, the last one being the most frequent aetiology. The collagenous gastritis is a rare entity and its association with collagenous colitis was exceptionally reported, only six cases being published. We report the seventh case of collagenous gastritis, ileitis and colitis in a 75-year-old woman with chronic diarrhea and important weight loss. This thickened subepithelial collagen band was appeared in an autoimmune injury context with antecedent of Hashimoto's thyroiditis and probably chronic atrophic Biermer's gastritis. The clinical and histological evolution was favourable with budesonide. PMID:20637552

  7. [Ulcerative colitis].

    PubMed

    Lopetuso, Loris; Gasbarrini, Antonio

    2016-06-01

    Inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the digestive tract resulting from dysregulated immune responses toward environmental factors in genetically predisposed individuals. This review focus on what is the state of the art of UC pathophysiology, diagnosis, and treatment and how any future findings could drive our clinical practice. PMID:27362722

  8. Increased Production of Lysozyme Associated with Bacterial Proliferation in Barrett's Esophagitis, Chronic Gastritis, Gluten-induced Atrophic Duodenitis (Celiac Disease), Lymphocytic Colitis, Collagenous Colitis, Ulcerative Colitis and Crohn's Colitis.

    PubMed

    Rubio, Carlos A

    2015-12-01

    The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory. PMID:26637845

  9. 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 ...

  10. 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

  11. Colitis after Hibiclens enema.

    PubMed

    Hardin, R D; Tedesco, F J

    1986-10-01

    Acute colitis occurred after a Hibiclens cleanser enema. Endoscopic and histologic features were not helpful in distinguishing this colitis from an infectious or idiopathic colitis, and a careful history proved invaluable. We review the complications of using soapsuds and various chemical-containing enemas; these complications range from mild colitis to death. Because soap and other chemicals are damaging to colonic mucosa, these enemas should be included as a cause of acute colitis.

  12. Microscopic colitis: pathologic considerations, changing dogma.

    PubMed

    Robert, Marie E

    2004-01-01

    Microscopic colitis as an entity was first recognized in 1976, and has become one of the most frequent diseases to exclude on colonic mucosal biopsies. In some pathology practices, up to 30% of colonic biopsies received are from patients in whom microscopic colitis is the clinical question. In this review, the evolution of the terminology and early studies describing the pathology of microscopic colitis are discussed. The pathology of lymphocytic and collagenous colitis is reviewed in detail, including common diagnostic pitfalls, and what is currently known about the pathogenesis of these diseases. The differential diagnosis of microscopic colitis includes other idiopathic inflammatory bowel diseases (Crohn's and ulcerative colitis), infections, and drug reactions. The distinction between these entities and microscopic colitis is discussed in detail. Finally, recent studies have revealed new histopathologic changes in microscopic colitis that challenge the currently held concepts of how microscopic colitis fits into the spectrum of inflammatory bowel diseases.

  13. [Collagenous gastritis and colitis in a 10-year-old girl].

    PubMed

    Hangard, P; Lasfargue, M; Rubio, A

    2016-07-01

    There are few data in the literature on microscopic gastritis and colitis in the pediatric population. The diagnosis is often made after the occurrence of complications. We report the case of a 10.5 year-old girl for whom the diagnosis was made several years after the initial symptoms. Test for infections, inflammation, and auto-immunity yielded normal results. Upper endoscopy and colonoscopy revealed an abnormal mucosa. However, histology showed microscopic inflammation and fibrotic lesions in the lamina propria, and a thick subepithelial collagenous band. This led to the diagnosis of collagenous gastritis and colitis. Budesonide treatment resulted in the cessation of diarrhea and significant weight gain. Treatment by oral budesonide indeed seems to be highly effective but relapses are frequent when the treatment is stopped. This case shows the importance of being vigilant regarding transit disorders with impact on growth kinetics. Upper endoscopy and colonoscopy need to be carried out when children have organic diarrhea with normal blood tests. PMID:27266639

  14. Is indeterminate colitis determinable?

    PubMed

    Tremaine, William J

    2012-04-01

    About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn’s disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn’s colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn’s disease, a subgroup are durably indeterminate. PMID:22314810

  15. Crohn's & Colitis Foundation of America

    MedlinePlus

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  16. 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

  17. 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. PMID:26470823

  18. Ulcerative Colitis in Infancy

    PubMed Central

    Rukunuzzaman, Md; Karim, A. S. M. Bazlul

    2011-01-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel's diverticulitis, Crohn's disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis. PMID:22064342

  19. Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis

    MedlinePlus

    ... scans use a combination of x rays and computer technology to create images. For a CT scan, ... video image of the intestinal lining to a computer screen, allowing the gastroenterologist to carefully examine the ...

  20. 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. PMID:27271790

  1. 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

  2. Glutaraldehyde-induced colitis

    PubMed Central

    Stein, Barry L.; Lamoureux, Esther; Miller, Mark; Vasilevsky, Carol-Ann; Julien, Lynne; Gordon, Philip H.

    2001-01-01

    Objective To describe the etiology and clinical course of acute colitis occurring after flexible endoscopy. Design Chart review. Setting A university teaching hospital. Patients Eight patients who sought assessment of potential colonic disease. Intervention Colonoscopy in 5 patients and flexible sigmoidoscopy in 3 patients. The indication for endoscopy was screening in 5 patients, cancer surveillance in 2 patients and preoperative evaluation of colon carcinoma in 1 patient. Outcome measures The relation of presenting symptoms to glutaraldehyde exposure, the response to therapy and the need for further therapy. Results All patients had abdominal pain, mucus diarrhea and rectal bleeding within 48 hours after endoscopy. Most patients reported that the symptoms started within 12 hours of the procedure. All patients were confirmed by sigmoidoscopy to have colitis within 72 hours of the first endoscopic procedure. One patient required hospitalization. In the first 7 patients several stool cultures were negative for Clostridium difficile using the cytotoxin assay by the cell culture method. Four patients had negative cultures for Yersinia, Salmonella and Shigella spp. Three patients were treated with metronidazole initially. Two patients underwent endoscopic biopsy and examination of the biopsy specimen showed fibrinoleukocytic exudate and ischemic type injury. One patient underwent the scheduled sigmoid resection within 48 hours of endoscopy for a Dukes’ stage B adenocarcinoma. Concomitant acute ischemic colitis limited to the mucosa and submucosa was noted in the resected specimen. Symptoms resolved in all patients and follow-up endoscopy revealed normal mucosa. Conclusion The entity of glutaraldehyde-induced colitis should be recognized and special attention should be given during instrument cleansing to minimize the risk of its development. PMID:11308232

  3. Management of ulcerative colitis

    PubMed Central

    Fell, John M; Muhammed, Rafeeq; Spray, Chris; Crook, Kay; Russell, Richard K

    2016-01-01

    Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects. PMID:26553909

  4. [Ulcerative colitis? Guidelines 2004].

    PubMed

    Siegmund, B; Zeitz, M

    2005-10-12

    Ulcerative colitis was first described in 1859 from Samuel Wilks, a physician at Guy's hospital in London. The prevalence in the high incidence areas ranges from 80 to 120/100.000/year. Ulcerative colitis is a chronic relapsing or chronic active disease which starts at the rectum and presents with a continuous inflammation. Primarily young adults are affected (20 to 40 years of age) but the disease may present at all ages, from younger than 1 year of life to the 80s. Many series show a secondary peak in incidence in the elderly. In the present review we will focus on the basic principles of the therapy with regard to the variety of disease manifestations. The therapeutic algorithms will be described separately for the induction of remission and the maintenance of remission. The localization of inflammation and disease activity represent crucial factors which have to be considered. With regard to these factors, the therapeutic regimens range from simple local therapy with aminosalicylates to systemic immunosuppressive therapy, which will in extreme cases require the administration of ciclosporin. Since ulcerative colitis is associated with an increased risk in developing colon carcinoma, medical therapy as well as endoscopic surveillance are fundamental in the prevention of carcinoma. In the end an outlook to future therapeutic targets and strategies will be provided. PMID:16245638

  5. Clostridium difficile colitis.

    PubMed

    Trnka, Y M; Lamont, J T

    1984-01-01

    Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract. PMID:6369936

  6. [Golimumab Therapy in Ulcerative Colitis].

    PubMed

    Moon, Won

    2016-02-01

    Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-α) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-α agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.

  7. Lymphocytic colitis: clinical presentation and long term course

    PubMed Central

    Mullhaupt, B; Guller, U; Anabitarte, M; Guller, R; Fried, M

    1998-01-01

    Background—Lymphocytic colitis is characterised by chronic watery diarrhoea with normal endoscopic or radiological findings and microscopic evidence of pronounced infiltration of the colonic mucosa with lymphocytes.
Aim—To investigate the long term clinical and histological evolution of the disease in a large group of patients with well characterised lymphocytic colitis. 
Methods—Between 1986 and 1995 the histological diagnosis of lymphocytic colitis was obtained in 35 patients; 27 of these agreed to a follow up examination. All clinical, endoscopic, and histopathological records were reviewed at that time and the patients had a second endoscopic examination with follow up biopsies. 
Results—The patients initially presented with the typical findings of lymphocytic colitis. After a mean (SD) follow up of 37.8 (27.5) months, diarrhoea subsided in 25 (93%) and histological normalisation was observed in 22 (82%) of the 27 patients. Progression from lymphocytic colitis to collagenous colitis was not observed. 
Conclusions—Lymphocytic colitis is characterised by a benign course with resolution of diarrhoea and normalisation of histology in over 80% of patients within 38 months. Considering the benign course of the disease, the potential benefit of any drug treatment should be carefully weighed against its potential side effects. 

 Keywords: lymphocytic colitis; colitis; diarrhoea PMID:9824342

  8. Genetics Home Reference: ulcerative colitis

    MedlinePlus

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

  9. 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

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

    PubMed

    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 (F0(DSS)), or non-supplemented tap water (F0(Ctrl)) 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 F0(DSS) males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0(DSS) 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 F0(Ctrl) males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  11. 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

  12. "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.

  13. 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)

  14. Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey

    PubMed Central

    Erdem, Levent; Yildirim, Sadik; Akbayir, Nihat; Yilmaz, Banu; Yenice, Necati; Gültekin, Orhan Sami; Peker, Önder

    2008-01-01

    AIM: To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey. METHODS: Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis (intraepithelial lymphocyte ≥ 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria) and collagenous colitis (subepithelial collagen band thickness ≥ 10 μm) were explored. RESULTS: Lymphocytic colitis was diagnosed in 12 (9%) patients (Female/Male: 7/5, mean age: 45 year, range: 27-63) and collagenous colitis was diagnosed in only 3 (2.5%) patients (all female, mean age: 60 years, range: 54-65). CONCLUSION: Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients. PMID:18666319

  15. β-lactam-associated eosinophilic colitis.

    PubMed

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-01-01

    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. PMID:26106168

  16. Substance P modulates colitis-associated fibrosis.

    PubMed

    Koon, Hon Wai; Shih, David; Karagiannides, Iordanes; Zhao, Dezheng; Fazelbhoy, Zafeer; Hing, Tressia; Xu, Hua; Lu, Bao; Gerard, Norma; Pothoulakis, Charalabos

    2010-11-01

    Substance P (SP) and the neurokinin-1 receptor (NK-1R) are involved in the development of colitis and mucosal healing after colonic inflammation. We studied whether SP modulates colonic fibrosis by using a chronic model of trinitrobenzenesulfonic acid (TNBS)-induced colitis in wild-type (WT) and NK-1R-deficient (NK-1R KD) mice. We found increased mRNA expression levels of collagen, vimentin, and the fibrogenic factors transforming growth factor β1 and insulin-like growth factor 1 in the chronically inflamed colons of WT mice treated with repeated intracolonic TNBS administrations. Fibrosis in TNBS-treated mice was also evident immunohistochemically by collagen deposition in the colon. Treatment of TNBS-exposed WT mice with the NK-1R antagonist CJ-12255 reduced colonic inflammation, colonic fibrosis, fibroblast accumulation, and expression levels of the fibrogenic factors. NK-1R knockout mice chronically exposed to TNBS had similar colonic inflammation compared with WT, but reduced colonic fibrosis, fibroblast accumulation, and expression levels of fibrogenic factors. Immunohistochemical staining also showed co-localization of NK-1R with fibroblasts in inflamed colons of mice and in colonic mucosa of patients with Crohn's disease. Exposure of human colonic CCD-18Co fibroblasts to SP (10 nmol/L) increased cell migration. SP stimulated collagen synthesis in CCD-18Co fibroblasts in the presence of transforming growth factor β1 and insulin-like growth factor 1, and this effect was reduced by Akt inhibition. Thus, SP, via NK-1R, promotes intestinal fibrogenesis after chronic colitis by stimulating fibrotic responses in fibroblasts. PMID:20889569

  17. Diagnosis and management of microscopic colitis: current perspectives.

    PubMed

    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.

  18. 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. PMID:27048897

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

    ClinicalTrials.gov

    2016-09-26

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

  20. Status of colitis-associated cancer in ulcerative colitis

    PubMed Central

    Kinugasa, Tetsushi; Akagi, Yoshito

    2016-01-01

    Surgical therapy for ulcerative colitis (UC) depends on the medical therapy administered for the patient’s condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer (CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients. PMID:27096030

  1. Factors precipitating acute ulcerative colitis.

    PubMed

    Puri, A S; Chaubal, C C; Midha, Vandana

    2014-08-01

    Ulcerative colitis is characterized by mucosal inflammation of a variable length of the colon starting from the rectum. The precise etiopathogenesis is unknown but it occurs in genetically susceptible individuals who manifest an abnormal immunological response against gut commensal bacteria. The disease course is-characterized by multiple spontaneous relapses and remissions. Two pathogens namely CMV and C. difficile have been associated with disease exacerbation in specific clinical situations. Whereas C. difficile may produce worsening of the disease in those exposed to broad spectrum antibiotics, CMV reactivation is seen only in patients with moderate to severe steroid refractory disease. The importance of these two super-infections can be gauged by the fact that both the ACG and the ECCO recommend testing for these two pathogens in appropriate clinical situations. The applicability of these guidelines in the Indian scenario has yet to be determined in view of the bacterial and parasitic infections endemic in tropical countries. The guidelines for diagnosis and management of these two super-infections in the presence of ulcerative colitis are discussed in this review. PMID:25735121

  2. Histological evaluation in ulcerative colitis.

    PubMed

    DeRoche, Tom C; Xiao, Shu-Yuan; Liu, Xiuli

    2014-08-01

    This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn's disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated

  3. 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.

  4. 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.

  5. Colitis

    MedlinePlus

    ... Elsevier Saunders; 2016:chap 116. Wald A. Other diseases of the colon and rectum. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  6. Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult: a case report.

    PubMed

    Hasegawa, Tsuyoshi; Aomatsu, Kazuki; Nakamura, Masanori; Aomatsu, Naoki; Aomatsu, Keiho

    2015-03-28

    We report a rare case of cytomegalovirus (CMV) colitis followed by severe ischemic colitis in a non-immunocompromised patient. An 86-year-old woman was admitted after experiencing episodes of vomiting and diarrhea. The next day, hematochezia was detected without abdominal pain. The initial diagnosis of ischemic colitis was based on colonoscopy and histological findings. The follow-up colonoscopy revealed a prolonged colitis. Immunohistochemical staining detected CMV-positive cells following conservative therapy. Intravenous ganciclovir therapy led to successful healing of ulcers and disappearance of CMV-positive cells. The prevalence of CMV infection is common in adults. CMV colitis is relatively common in immunocompromised patients; however, it is rare in immunocompetent patients. In our case, CMV infection was allowed to be established due to the disruption of the colonic mucosa by the prior severe ischemic colitis. Our experience suggests that biopsies may be necessary to detect CMV and the prompt management of CMV colitis should be instituted when intractable ischemic colitis is observed.

  7. 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

  8. Intravenous Immunoglobulin in the Treatment of Severe Clostridium Difficile Colitis

    PubMed Central

    Shah, Nihar; Shaaban, Hamid; Spira, Robert; Slim, Jihad; Boghossian, Jack

    2014-01-01

    Intravenous immunoglobulin (IVIG) has been utilized in patients with recurrent and refractory Clostridium difficile colitis. It is increasingly being used in patients with initial clinical presentation of severe colitis. Herein, we report a case of severe C. Difficile colitis successfully treated with IVIG with a review of the medical literature to identify the optimal timing and clinical characteristics for this treatment strategy. PMID:24926170

  9. 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.

  10. Segmental colitis associated diverticulosis syndrome.

    PubMed

    Freeman, Hugh J

    2016-09-28

    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

  11. [Antibiotic treatment of clostridial colitis].

    PubMed

    Beneš, J; Polívková, S

    2016-01-01

    The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant). Fidaxomicin works faster than vancomycin and is associated with a lower risk of recurrence. Thus, it can be profitably used in patients with impending ileus and also in those whose medical condition does not allow prolonged treatment. The duration of fidaxomicin treatment could be reduced to as few as five days. Rifaximin does not have a clear place in the treatment of CDI because no compelling data are available on its efficacy in this disease. The risk of resistance is also important. Tigecycline is a promising antibiotic for parenteral use. According to the available data, it should be more effective than intravenous metronidazole which has been considered the drug of choice.Clostridial colitis is associated with intestinal dysmicrobia which is the major cause of recurrence. Severe dysmicrobia cannot be treated by antibiotics but only by gut flora restoration; stool transplant from a healthy donor is the only proven therapy for this condition. PMID:27246640

  12. 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

  13. 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. PMID:26365308

  14. Amyloid Goiter Secondary to Ulcerative Colitis.

    PubMed

    Aydin, Bunyamin; Koca, Yavuz Savas; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  15. Biomarkers for colitis-associated colorectal cancer.

    PubMed

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-09-21

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  16. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID:27672285

  17. Biomarkers for colitis-associated colorectal cancer

    PubMed Central

    Chen, Ru; Lai, Lisa A; Brentnall, Teresa A; Pan, Sheng

    2016-01-01

    Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer.

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

    SciTech Connect

    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, which was characterized by inhomogeneous attenuation and a target appearance of the rectum, and proliferation of perirectal fat. Bowel wall thickening 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.

  19. Drug therapy for ulcerative colitis

    PubMed Central

    Xu, Chang-Tai; Meng, Shu-Yong; Pan, Bo-Rong

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole. Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn’s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfa-free 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds, systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.) are potent and fast-acting drugs for treating UC, Crohn’s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC. Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP, methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC. PMID:15285010

  20. Rectal mucocoele following subtotal colectomy for colitis.

    PubMed

    Appleton, N; Day, N; Walsh, C

    2014-09-01

    We present a unique case of a rectal mucocoele affecting a patient several years after his subtotal colectomy for ulcerative colitis. This was secondary to both a benign anorectal stenosis and a benign mucus secreting rectal adenoma. This case highlights the importance of surveillance in such patients.

  1. Ulcerative colitis flare with splenic ven thrombosis.

    PubMed

    Bozkurt, Huseyin Sancar; Kara, Banu; Citil, Serdal

    2015-01-01

    Patients with ulcerative colitis (UC) have an increased risk of thromboembolic events. Here, we present a 28-year-old man with active ulcerative pancolitis presenting via splenic vein thrombosis and left renal superior infarct that was not associated with a surgical procedure.

  2. RNase-L deficiency exacerbates experimental colitis and colitis-associated cancer

    PubMed Central

    Long, Tiha M.; ArindamChakrabarti; Ezelle, Heather J.; E. Brennan-Laun, Sarah; Raufman, Jean-Pierre; Polyakova, Irina; H. Silverman, Robert; Hassel, Bret A.

    2013-01-01

    Background The endoribonuclease RNase-L is a type-I interferon (IFN)-regulatedcomponent of the innate immune response that functions in antiviral, antibacterial and antiproliferative activities. RNase-L produces RNA agonists of RIG-I-like receptors (RLRs), sensors of cytosolic pathogen-associated RNAs that induce cytokines including IFNβ. IFNβ and RLR signaling mediate protective responses against experimental colitis and colitis-associated cancer (CAC) and contribute to gastrointestinal (GI) homeostasis. Therefore, we investigated a role for RNase-L in murine colitis and CAC and its association with RLR signaling in response to bacterial RNA. Methods Colitis was induced in wild type (WT) and RNase-L-deficient mice (RNase-L−/−) by administration of dextran sulphate sodium (DSS). CAC was induced by DSS and azoxymethane (AOM). Histological analysis and immunohistochemistry were performed on colon tissue to analyze immune cell infiltration and tissue damage following induction of colitis. Expression of cytokines was measured by qRT-PCR and ELISA. Results DSS-treated RNase-L−/− mice exhibited a significantly higher clinical score, delayed leukocyte infiltration, reduced expression of IFNβ, TNFα, IL-1β and IL-18at early times post-DSS exposure and increased mortalityas compared to WT mice. DSS/AOM-treated RNase-L−/−mice displayed an increased tumor burden. Bacterial RNA triggeredIFNβproductionin an RNase-L-dependent manner and provided a potential mechanism by whichRNase-L contributes to the GI immune response to microbiota and protects against experimental colitis and CAC. Conclusions RNase-L promotes the innate immune response to intestinal damage and ameliorates murine colitis and CAC. The RNase-L-dependent production of IFNβ stimulated by bacterial RNA may be a mechanism to protectagainst GI inflammatory disease. PMID:23567782

  3. Dextran sulfate sodium (DSS)-induced colitis in mice.

    PubMed

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

    2014-01-01

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (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 must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology. PMID:24510619

  4. Dextran sulfate sodium (DSS)-induced colitis in mice.

    PubMed

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

    2014-02-04

    Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (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 must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology.

  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. Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn’s colitis

    PubMed Central

    Ballard, Billy Ray; M’Koma, Amosy Ephreim

    2015-01-01

    Patients with indeterminate colitis (IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis (UC) or Crohn’s colitis (CC) which is not offered in 15%-30% of inflammatory bowel disease (IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry (MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as being either a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis. PMID:26140094

  7. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis.

    PubMed

    Liu, Weicheng; Chen, Yunzi; Golan, Maya Aharoni; Annunziata, Maria L; Du, Jie; Dougherty, Urszula; Kong, Juan; Musch, Mark; Huang, Yong; Pekow, Joel; Zheng, Changqing; Bissonnette, Marc; Hanauer, Stephen B; Li, Yan Chun

    2013-09-01

    The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4(+)CD45RB(hi) T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.

  8. 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.

  9. Allergic colitis in monozygotic preterm twins.

    PubMed

    Baldassarre, Maria Elisabetta; Cappiello, Annarita; Laforgia, Nicola; Vanderhoof, Jon

    2013-02-01

    Allergic colitis (AC) typically develops in the first weeks or months of life and is characterized by the presence of red blood in the stools of healthy breastfed or formula fed infants. In this paper, we describe a case of rectal bleeding in monozygotic preterm twins that was resolved with the introduction of a cow's milk protein-free diet (CMPFD). The occurrence of this disorder in monozygotic twins raises the question as to whether the underlying abnormality in the immune regulation, which leads to poor acquisition of tolerance to cow's milk proteins, might be inherited or environmentally acquired. The case also highlights the use of the probiotic Lactobacillus GG (LGG) in the treatment of allergic colitis. PMID:23098248

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats

    PubMed Central

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A.; Yaylali, Aslı; 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. PMID:26246013

  16. 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.

  17. 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

  18. Group A beta-hemolytic streptococcal colitis with secondary bacteremia.

    PubMed

    Arthur, Ciji; Linam, Leann E; Linam, W Mathew

    2012-10-01

    We report a case of a 5-year-old girl with invasive colitis and secondary bacteremia caused by group A beta-hemolytic streptococcus. Although group A beta-hemolytic streptococcus is occasionally isolated from stool, it is a rare cause of colitis. This is the first report of group A beta-hemolytic streptococcus pancolitis with secondary bacteremia.

  19. A case of Reiter's disease complicated by fulminating colitis.

    PubMed Central

    Hickling, P; Martin, M F; Brooks, S

    1982-01-01

    We describe a patient who, 6 months after the onset of Reiter's disease associated with a destructive peripheral arthritis and keratodermia blenorrhagica, developed fulminating colitis. The possible relationship between Reiter's disease and ulcerative colitis is discussed, and the need for further family studies to assess its validity is stressed. Images PMID:7073347

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

    PubMed

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

    2014-01-01

    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.

  1. Arthropathy, ankylosing spondylitis, and clubbing of fingers in ulcerative colitis

    PubMed Central

    Jalan, K. N.; Prescott, R. J.; Walker, R. J.; Sircus, W.; McManus, J. P. A.; Card, W. I.

    1970-01-01

    In a retrospective study of 399 patients with ulcerative colitis, 27 patients had colitic arthritis, 17 had ankylosing spondylitis, and 20 had clubbing of the fingers. Colitic arthritis and ankylosing spondylitis were not related to severity, extent of involvement, or duration of colitis. A significant association between colitic arthropathy and other complications of ulcerative colitis, such as pseudopolyposis, perianal disease, eye lesions, skin eruptions, aphthous ulceration, and liver disease has been demonstrated. The outcome of the first referred attack of colitis in the presence of colitic arthritis and ankylosing spondylitis remained uninfluenced. Clubbing of fingers was related to severity, extent of involvement, and length of the history of colitis. A significant association between clubbing of the fingers and carcinoma of the colon, pseudopolyposis, toxic dilatation, and arthropathy has been shown. The frequency of surgical intervention in patients with clubbing was higher but the overall mortality was not significantly different from the patients without clubbing. PMID:5473606

  2. Prostaglandin ethanolamides attenuate damage in a human explant colitis model.

    PubMed

    Nicotra, Lauren L; Vu, Megan; Harvey, Benjamin S; Smid, Scott D

    2013-01-01

    Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon. PMID:23380599

  3. Colonic biogeography in health and ulcerative colitis.

    PubMed

    Lavelle, Aonghus; Lennon, Grainne; Winter, Desmond C; O'Connell, P Ronan

    2016-09-01

    The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome. PMID:27662587

  4. Grim19 Attenuates DSS Induced Colitis in an Animal Model.

    PubMed

    Kim, Jae-Kyung; Lee, Seung Hoon; Lee, Seon-Young; Kim, Eun-Kyung; Kwon, Jeong-Eun; Seo, Hyeon-Beom; Lee, Han Hee; Lee, Bo-In; Park, Sung-Hwan; Cho, Mi-La

    2016-01-01

    DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation.

  5. Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

    PubMed Central

    Nowarski, Roni; Jackson, Ruaidhrí; Gagliani, Nicola; de Zoete, Marcel R.; Palm, Noah W.; Bailis, Will; Low, Jun Siong; Harman, Christian C.D.; Graham, Morven; Elinav, Eran; Flavell, Richard A.

    2016-01-01

    SUMMARY The intestinal mucosal barrier controlling the resident microbiome is dependent on a protective mucus layer generated by goblet cells, impairment of which is a hallmark of the inflammatory bowel disease Ulcerative Colitis. Here we show that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells (Δ/EC) conferred protection from colitis and mucosal damage in mice. In contrast, deletion of the IL-18 negative regulator Il18bp resulted in severe colitis associated with loss of mature goblet cells. Colitis and goblet cell loss were rescued in Il18bp−/−;Il18rΔ/EC mice, demonstrating that colitis severity is controlled at the level of IL-18 signaling in intestinal epithelial cells. IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction which underlies the pathology of Ulcerative Colitis. PMID:26638073

  6. Diagnosis and classification of ulcerative colitis.

    PubMed

    Conrad, Karsten; Roggenbuck, Dirk; Laass, Martin W

    2014-01-01

    Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD) characterised by superficial mucosal ulceration, rectal bleeding, diarrhoea, and abdominal pain. In contrast to Crohn's disease (CrD), UC is restricted to the colon and the inflammation is limited to the mucosal layer. Classic UC affects the colon in a retrograde and continuous fashion starting from the rectum and extending proximally. Dependent on the anatomic extent of involvement, UC can be classified as proctitis, left-sided colitis, or pancolitis. Inflammatory arthropathies and primary sclerosing cholangitis (PSC) are the most common and clinically most important extraintestinal manifestations of UC. The aetiopathogenesis of UC is incompletely understood, but immune-mediated mechanisms are responsible for dysregulated immune responses against intraluminal antigens in genetically predisposed individuals. The diagnosis is based on the history, as well as clinical, radiological, endoscopic and histological features. Autoantibodies, mainly antineutrophil cytoplasmic antibodies (ANCA) and anti-goblet cell antibodies (GAB) may be helpful in the early diagnosis of UC and in differentiating it from CrD.

  7. Ulcerative Colitis and Immunoglobulin G4

    PubMed Central

    Kuwata, Go; Koizumi, Koichi; Tabata, Taku; Hara, Seiichi; Kuruma, Sawako; Fujiwara, Takashi; Chiba, Kazuro; Egashira, Hideto; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Horiguchi, Shinichiro

    2014-01-01

    Background/Aims Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). Conclusions UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity. PMID:24516698

  8. 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

  9. Paclitaxel-carboplatin induced radiation recall colitis.

    PubMed

    Kundak, Isil; Oztop, Ilhan; Soyturk, Mujde; Ozcan, Mehmet Ali; Yilmaz, Ugur; Meydan, Nezih; Gorken, Ilknur Bilkay; Kupelioglu, Ali; Alakavuklar, Mehmet

    2004-01-01

    Some chemotherapeutic agents can "recall" the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.

  10. Infectious Colitis Associated With Ipilimumab Therapy

    PubMed Central

    McCutcheon, Jessica L.; McClain, Colt M.; Puzanov, Igor; Smith, Terrence A.

    2014-01-01

    Ipilimumab is a monoclonal antibody against cytotoxic T lymphocyte-associated molecule-4 and is thought to promote anti-tumor activity by enhancing cell mediated immunity. It is one of the few therapies shown to improve overall survival in metastatic melanoma. Given its mechanism of action, the drug is associated with significant immune-related adverse events with the gastrointestinal system being commonly involved. Our patient is a 22-year-old female with stage IVA melanoma on ipilimumab therapy who presented with fever, diarrhea and abdominal pain. She gave a history of recent travel to a wedding where several other guests in attendance had also developed diarrheal illnesses. Her colonoscopy and pathology were consistent with ipilimumab-induced colitis. Her stool culture returned positive for Salmonella enteritides. She was treated with prednisone and ciprofloxacin with resolution of her symptoms. In our case, we describe ipilimumab-induced colitis where an infectious pathogen was identified with temporal relationship to symptoms and could be suggestive of a causal relationship.

  11. Golimumab: clinical update on its use for ulcerative colitis.

    PubMed

    Gilardi, D; Fiorino, G; Allocca, M; Bravatà, I; Danese, S

    2015-03-01

    Monoclonal antibodies directed against tumor necrosis factor alpha (anti-TNF-α agents) have dramatically changed the therapeutical approach to inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. A new anti-TNF drug, golimumab, has recently been approved for patients with moderate to severe ulcerative colitis. Its efficacy has been demonstrated by preclinical and clinical studies and the drug showed an efficacy and safety profile in line with the other anti-TNF agents, such as infliximab and adalimumab. This review gives an overview on golimumab in the treatment of moderate to severe ulcerative colitis.

  12. 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

  13. 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.

  14. 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. PMID:2991089

  15. 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

  16. 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)

  17. 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.

  18. Probiotics in the Management of Ulcerative Colitis.

    PubMed

    Chibbar, Richa; Dieleman, Levinus A

    2015-01-01

    Rapid progress has been made to understand the pathophysiology of inflammatory bowel diseases and to identify new treatments. Interaction of the gut microbiota on the host inflammatory response has suggested that alternative therapies, such as probiotics, might have a complementary role in treating and preventing disease flares. Multiple probiotics and their formulations have been studied for both the induction and maintenance of remission of ulcerative colitis (UC); however, mainly Escherichia coli Nissle 1917 and VSL#3 have been shown to provide significant benefits for the prevention and treatment of mild to moderate UC. Although these data are promising, there is still a paucity of robust, randomized-controlled trials to suggest that probiotics be utilized as part of a standard treatment regimen. With continued research and a movement toward carefully selected, individualized management based on an individual's specific microbiota composition and function, probiotics may become an integral part of tailored therapy for UC. PMID:26447965

  19. Ulcerative colitis and Crohn's disease tissue cytotoxins

    SciTech Connect

    McLaren, L.C.; Gitnick, G.

    1982-06-01

    Bowel-wall tissue filtrates from patients with inflammatory bowel disease produce cytopathic effects in tissue culture. The cytopathic effects inducers have been reported to have the characteristics of a small RNA virus. Clostridium difficile toxin also produces cytopathic effects and has been found in the stools of patients with Crohn's disease and ulcerative colitis. The present study concerns the further characterization of the cytopathic inducers in tissues of inflammatory bowel disease patients. It was found that they are nonsedimentable at 148,000 g for 2 h and resistant to inactivation by UV light. They are proteins that are distinct from C. difficile toxin and are unique cytotoxins which are associated with the early cytopathic effects observed in Riff-free chick embryo and rabbit ileum cell cultures. These results suggest that the early cytopathic effects previously described are not produced by a virus. They do not explain the delayed cytopathic effects seen in rabbit ileum or WI-38 cells.

  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. Treatment of severe steroid refractory ulcerative colitis

    PubMed Central

    Assche, Gert Van; Vermeire, Séverine; Rutgeerts, Paul

    2008-01-01

    Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg IV, 0-2-6 wk) or total colectomy. The choice between these three options is a medical-surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections. PMID:18810767

  2. 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

  3. 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.

  4. An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4+ T Cells

    PubMed Central

    Nyhlin, Nils; Wickbom, Anna; Bohr, Johan; Hultgren, Olof; Hultgren Hörnquist, Elisabeth

    2014-01-01

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4+ T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1β and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4+ T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines. PMID:25332518

  5. Nitric oxide increases Wnt-induced secreted protein-1 (WISP-1/CCN4) expression and function in colitis.

    PubMed

    Wang, Hongying; Zhang, Rui; Wen, Shoubin; McCafferty, Donna-Marie; Beck, Paul L; MacNaughton, Wallace K

    2009-04-01

    Nitric oxide (NO) derived from the inducible NO synthase (iNOS) is an important and complex mediator of inflammation in the intestine. Wnt-inducible secreted protein (WISP)-1 (CCN4), a member of the connective tissue growth factor family, is involved in tissue repair. We sought to determine the relationship between iNOS and WISP-1 in colitis. By analyzing human colonic biopsy samples, we showed that the expression of mRNA for both iNOS and WISP-1 was significantly higher in ulcerative colitis samples compared with control tissue. The upregulation of WISP-1 was positively correlated with iNOS expression in two models of colitis, induced by intrarectal trinitrobenzenesulfonic acid (TNBS) or occurring spontaneously in IL-10 deficient mice. Loss of iNOS, studied using iNOS(-/-) mice in both TNBS-induced and IL-10(-/-) colitis models, significantly attenuated the colitis-related WISP-1 increase. In human colonic epithelial cell lines, the NO donor, DETA-NONOate, elevated WISP-1 mRNA and protein expression through a beta-catenin and CREB-dependent, but Wnt-1-independent, pathway. In addition, NO-induced WISP-1 directly induced secretion of soluble collagen in colonic fibroblast cells. NO increases WISP-1 expression both in vitro and in vivo, suggesting a new role for iNOS and NO in colitis.

  6. 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. PMID:25766132

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Refractory ulcerative colitis accompanied with cytomegalovirus colitis and multiple liver abscesses: a case report.

    PubMed

    Inoue, Takuya; Hirata, Ichiro; Egashira, Yutaro; Ishida, Kumi; Kawakami, Ken; Morita, Eijiro; Murano, Naoko; Yasumoto, Shingo; Murano, Mitsuyuki; Toshina, Ken; Nishikawa, Takashi; Hamamoto, Norihiro; Nakagawa, Ken; Katsu, Ken-Ichi

    2005-09-01

    Various hepato-biliary complications are an increased incidence in patients with inflammatory bowel disease, and portal bacteremia is well documented in patients with ulcerative colitis (UC). However, few reports mention UC in association with liver abscesses. Recently, there are several reports describing cytomegalovirus (CMV) infection in association with disease exacerbation and steroid refractoriness in patients with UC. Here we present a case of refractory UC accompanied with multiple liver abscesses and CMV colitis. The patient, a 72-year-old male, with a five-year history of repeated admissions to our hospital for UC, presented with an exacerbation of his UC. Sigmoidoscopy performed on admission suggested that his UC was exacerbated, then he was given prednisolone and mesalazine orally, and betamethasone enemas. However, he had exacerbated symptoms. Repeat sigmoidoscopy revealed multiple longitudinal ulcers and pseudopolyps in the rectosigmoid colon. Although immunohistochemical staining of biopsy specimens and the serum testing for antigenemia were negative on admission and after the repeat sigmoidoscopy, they became histologically positive for CMV. Nonetheless, the patient developed spiking fevers, soon after ganciclovir was administered. Laboratory studies revealed an increased white cell count with left shift, and Enterococcus fecalis grew in blood cultures. An abdominal computed tomography (CT) scan was obtained and the diagnosis of liver abscesses associated with UC was made, based on CT results. The hepatic abscesses were successfully treated with intravenous meropenem for 6 wk, without further percutaneous drainage. To our knowledge, this is the first reported case of multiple liver abscesses that develop during UC exacerbation complicated by CMV colitis. PMID:16127763

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Radical induction theory of ulcerative colitis

    PubMed Central

    Pravda, Jay

    2005-01-01

    To propose a new pathogenesis called Radical Induction to explain the genesis and progression of ulcerative colitis (UC). UC is an inflammatory bowel disease. Colonic inflammation in UC is mediated by a buildup of white blood cells (WBCs) within the colonic mucosal lining; however, to date there is no answer for why WBCs initially enter the colonic mucosa to begin with. A new pathogenesis termed “Radical Induction Theory” is proposed to explain this and states that excess un-neutralized hydrogen peroxide, produced within colonic epithelial cells as a result of aberrant cellular metabolism, diffuses through cell membranes to the extracellular space where it is converted to the highly damaging hydroxyl radical resulting in oxidative damage to structures comprising the colonic epithelial barrier. Once damaged, the barrier is unable to exclude highly immunogenic fecal bacterial antigens from invading the normally sterile submucosa. This antigenic exposure provokes an initial immune response of WBC infiltration into the colonic mucosa. Once present in the mucosa, WBCs are stimulated to secrete toxins by direct exposure to fecal bacteria leading to mucosal ulceration and bloody diarrhea characteristic of this disease. PMID:15832404

  14. Relapsing and refractory ulcerative colitis in children.

    PubMed

    Turner, Dan

    2014-01-01

    Approximately half of the children with ulcerative colitis (UC) have refractory, relapsing or steroid-dependent disease. UC in children is more extensive than in adults, presents more often with severe attacks and carries a more aggressive disease course. Therefore, although a step-up approach is usually recommended in UC, aggressive therapy will often be indicated in children since steroid dependency should never be tolerated. It is vital to ensure that in every resistant case, the symptoms are truly related to the inflammatory disease activity and not to other conditions such as poor adherence to treatment, infections, adverse reactions to drugs, irritable bowel syndrome, lactose intolerance, celiac disease and bacterial overgrowth. The clinician should be ready to escalate therapy in a timely manner but only after ensuring optimization of current treatments. Optimization may include, among others, appropriate dosage, utilization of assays that determine thiopurine, calcineurin inhibitors and anti-tumor necrosis factor levels, introduction of combination therapy when indicated (enemas and immunomodulators) and a long enough time for treatment to become effective. Colectomy is always a valid option and should be discussed before major treatment escalations. Experimental therapies can be considered when all else fails and the family prefers to avoid colectomy. The management of refractory and relapsing disease is particularly challenging in children, and this review summarizes the available evidence to guide treatment decisions in this setup. PMID:24969290

  15. 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

  16. Surveillance issues in inflammatory bowel disease: ulcerative colitis.

    PubMed

    Provenzale, D; Onken, J

    2001-02-01

    This review article on the surveillance of patients with ulcerative colitis provides an overview of the criteria for evaluating screening and surveillance programs and applies the criteria to the available evidence to determine the effectiveness of the surveillance of patients with ulcerative colitis. We examine the clinical outcomes associated with surveillance, the additional clinical time required to confirm the diagnosis of dysplasia and cancer, compliance with surveillance and follow-up, and the effectiveness of the individual components of a surveillance program, including colonoscopy and pathologist's interpretation. The disability associated with colectomy is considered, as are the cost and acceptability of surveillance programs. Patients with long-standing ulcerative colitis are at risk for developing colorectal cancer. Recommended surveillance colonoscopy should be supported. New endoscopic and histopathologic techniques to improve the identification of high-risk patients may enhance the effectiveness and cost-effectiveness of surveillance practices.

  17. Microscopic colitis: a new cause of chronic diarrhea in children?

    PubMed

    Mashako, M N; Sonsino, E; Navarro, J; Mougenot, J F; Gargouri, A; Boige, N; Cezard, J P

    1990-01-01

    From a retrospective study on children who underwent colonoscopy or rectosigmoidoscopy with multiple level biopsies, we selected five patients whose rectocolonic endoscopic aspect was normal and contrasting with the presence of a microscopic colitis on biopsies. These five children had chronic diarrhea (mean duration of 14 months), associated with vomiting (three cases), abdominal pain (two cases), anorexia (two cases), abdominal distension (two cases), and weight loss (four cases). Symptomatic treatment was used in all children: loperamide (one case), trimebutine (three cases), and aluminium and magnesium silicate (two cases). One child received sulfasalazine for 2 months. After 1 year, all patients had normal stools. Rectosigmoidoscopy was performed in four patients and was normal. Biopsies obtained in three cases were normal in two cases and showed a persistent microscopic colitis in one case. Microscopic colitis may be a distinct cause of chronic diarrhea in children. PMID:2324876

  18. [Ulcerative colitis and proctitis in two Swiss Braunvieh cows].

    PubMed

    Braun, U; Hilbe, M; Gerspach, C; Ruetten, M

    2015-04-01

    Two Swiss Braunvieh cows were referred to our clinic because of narrowing of the rectum and difficult rectal examination attributable to restricted arm movement within the pelvic cavity. Cow 1 also had perforation of the cranial rectum and cow 2 had multiple small funnel-shaped depressions in the rectal mucosa. Both cows had ultrasonographic evidence of peritonitis with thickening of the intestinal wall and fibrin and fluid accumulation in the abdominal cavity. A diagnosis of peritonitis was made in both cows, most likely caused by rectal perforation; they were euthanized and a post-mortem examination was carried out. Both cows had proctitis and ulcerative colitis with three or four perforated ulcers which were associated with fibrinopurulent peritonitis. The final diagnosis was ulcerative colitis and proctitis of unknown aetiology. Infectious causes of colitis and proctitis, including bovine viral diarrhoea, adenovirus infection and salmonellosis, and trauma and poisoning were ruled out.

  19. 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.

  20. Long-term prognosis of children with ulcerative colitis

    PubMed Central

    Goel, K. M.; Shanks, Robert A.

    1973-01-01

    The subsequent course of ulcerative colitis in 25 children admitted to hospital during the period 1931 to 1971 is reviewed. The period of observation averaged 24 years, ranging from 1 to 41 years. 19 patients showed extracolonic manifestations. 4 patients had a single attack of colitis, and in 19 the disease was of the chronic intermittent type. There was one case each of the acute fulminating and chronic continuous types. Three of 8 patients who had colectomy died postoperatively. One further patient died later of carcinoma of the rectal stump. At follow-up 5 patients (20%) had died and the remaining 20 (80%) were in remission. Although the case for surgery in the treatment of acute fulminating or resistant ulcerative colitis may be clear, that for prophylactic panproctocolectomy while the disease is in remission requires further study. PMID:4703063

  1. 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

  2. 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.

  3. 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. PMID:27179305

  4. 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

  5. Tracheobronchitis as an extraintestinal manifestation of ulcerative colitis

    PubMed Central

    Javia, Siddharth; Agrawal, Abhinav; Patell, Rushad; Jasdanwala, Sarfaraz

    2014-01-01

    Respiratory involvement is a rare extraintestinal manifestation of ulcerative colitis (UC). It commonly presents as bronchiectasis and rarely as tracheobronchitis. It can occur before or after the presentation of gastrointestinal symptoms. Only rarely does it occur after the patient undergoes colectomy. Diagnosis should be considered in any patient with UC who presents with unexplained upper respiratory symptoms and a negative work up for infectious aetiologies. It responds well to immunosuppressive therapy. We present a case of a 21-year-old woman who underwent colectomy for ulcerative colitis and later presented with new onset severe reversible inflammation of the upper respiratory tract. PMID:25326560

  6. [Hemolytic anemia and dysenteric syndrome: a case of ulcerative colitis].

    PubMed

    Claes, G; Colard, M; Benghiat, F S; Maerevoet, M; Bailly, B; De Wilde, V

    2015-01-01

    A 53-years-old man has a dysentery since two weeks. The blood test shows Coombs-positive hemolytic anemia and inflammation. Autoimmune hemolytic anemia (AIHA) is treated with corticosteroid. A colonoscopy reveals an ulcerative colitis. The evolution of the patient is complicated by a spontaneous digestive perforation treated by total proctocolectomy. After this intervention, there is a resolution of the AIHA and the patient is gradually weaned from corticosteroids. AIHA is a rare extra-intestinal manifestation of inflammatory bowel disease essentially ulcerative colitis. Identification of this cause of secondary AIHA is important for the therapeutic strategy. However treatment is nonspecific and based on low levels of evidence.

  7. Bowel obsession syndrome in a patient with ulcerative colitis.

    PubMed

    Porcelli, Piero; Leandro, Gioacchino

    2007-01-01

    Gastroenterologists are often faced with the diagnostic problem of differentiating acute symptoms of ulcerative colitis from functional intestinal disorders. Bowel obsession syndrome (BOS) is an OCD-like, functional syndrome characterized by fear of fecal incontinence and compulsive behaviors of evacuation-checking. Only sparse case studies on treatment of BOS with antidepressants have been published. This is the first study on successful psychotherapy of a male patient with ulcerative colitis overlapping functional bowel symptoms and marked symptoms of BOS. Clinical recognition of BOS may help clinicians in differential diagnosis, prevent unnecessary investigations, and give patients the most appropriate treatment.

  8. High chromogranin A cell density in the colon of patients with lymphocytic colitis.

    PubMed

    El-Salhy, M; Lomholt-Beck, B; Gundersen, T D

    2011-01-01

    Microscopic colitis (MC) is a chronic condition that is characterized by watery diarrhoea with normal appearance of the colonic mucosa. MC is subdivided into two distinctive entities: lymphocytic colitis (LC) and collagenous colitis (CC). The etiology and pathophysiology of LC remain to be determined. The present study included 9 female patients with LC, with an average age of 34 years. Subjects (n=25) who underwent colonoscopy were used as controls. The subjects underwent colonoscopy due to gastrointestinal bleeding, where the source of bleeding was identified as haemorrhoids, or due to health concerns. The control subjects included 18 females and 7 males, with an average age of 49 years. Colonoscopy was performed in both patient and control groups, and biopsies were obtained from different segments of the colon. The biopsies were immunostained with the avidin-biotin complex method for human leucocytes CD45, collagen type III and chromogranin A (CgA). CgA was quantified by computer image analysis. The density of CgA-immunoreactive cells in patients with LC was significantly higher than that in controls. The high density of colonic CgA, a common marker for endocrine cells, indicates the possibility that colonic hormones are involved in the pathophysiology of LC. Serotonin-containing cells are the major endocrine cell type in the colon and constitute approximately 88% of the total endocrine cell population. It is likely that the increase in colonic CgA in LC patients accounts for an increase in serotonin cells. PMID:21584496

  9. 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

  10. Severe acute ulcerative colitis: the pediatric perspective.

    PubMed

    Turner, Dan

    2009-01-01

    Many features of pediatric ulcerative colitis (UC) are similar to adult-onset disease, but the rate of extensive disease is doubled in children. It is, therefore, not surprising that the admission rate for severe UC is higher in childhood-onset UC, reaching 28% by the age of 16 years. Approximately 30-40% of children will fail corticosteroids and require second-line medical therapy or colectomy. A pediatric UC activity index (PUCAI) score of >65 indicates severe disease and the index can assist in determining the need and timing of second-line medical therapy or colectomy early during the admission. A PUCAI score of >45 points on day 3 identify patients likely to fail corticosteroids (negative predictive value 90-95%), and a score >70 points on day 5 identify patients who will require short-term treatment escalation (positive predicting value 95-100%). Data in children are limited, but it seems that cyclosporine, tacrolimus and infliximab achieve a similar short-term response rate, in the range of 60-80%. Infliximab has the advantage that it may be given for a prolonged period of time while calcineurin inhibitors should not be used for more than 3-4 months, bridging to a thiopurine regimen. Colectomy is indicated in toxic megacolon or in cases refractory to one salvage therapy. The choice of colectomy in other cases should carefully consider its effect on the patient's quality of life, its impact on the physical and emotional development at a critical age of personality development, and its association with a high infertility rate in females undergoing pouch procedure before childbearing age.

  11. Early surgical intervention for fulminant pseudomembranous colitis.

    PubMed

    Ali, Syed O; Welch, John P; Dring, Robert J

    2008-01-01

    The objective of this study of a retrospective case series was to determine factors associated with survival after surgical intervention in pseudomembranous colitis (PMC). The study was conducted at a tertiary care medical center and comprised 36 patients who underwent colectomy for fulminant PMC from 1995 to 2006. Patients including 21 females ranged from 40 to 89 years of age (mean, 70 years). Comorbidities included diabetes (39%), cardiovascular disease (77%), chronic obstructive pulmonary disease (47%), and intake of immunosuppressive medications (45%). Seventy-two per cent received antibiotics in the previous 2 months. Only patients with a confirmation of PMC on pathology specimens were included in the study. All patients underwent colectomy. Patients were stratified into two groups: survivors and nonsurvivors. Various clinical factors/ parameters used in the management of patients with PMC were studied in these two groups. Survival was correlated with mean white blood cell count (23,000 survivors versus 40,000 nonsurvivors, P < 0.01); multisystem organ failure (16 per cent survivors versus 47 per cent nonsurvivors, P < 0.05); and preoperative pressors (16 per cent survivors versus 47 per cent nonsurvivors, P < 0.05). Overall mortality for the study period was 47 per cent. Mortality rate analysis revealed a lower rate for the more recent years (32 per cent for 2000 to 2006 versus 65 per cent for 1995 to 1999, P < 0.05). In the more recent years, the time elapsing before colectomy was also lower (1.4 days versus 2.5 days, nonsignificant), and patients had less preoperative hemodynamic instability (70 per cent versus 31 per cent, P < 0.03). In one institution, survival after surgery for PMC was found to be associated with a mean white blood cell count (< 37,000), nondependence on preoperative vasopressors, and surgical intervention before the onset of hemodynamic instability. PMID:18274423

  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. Diagnostic imaging advances in murine models of colitis

    PubMed Central

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

    2016-01-01

    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. PMID:26811642

  14. 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)

  15. 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.

  16. 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.

  17. 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. PMID:25523228

  18. [Ischemic colitis after renal transplantation:etiology and pathogenesis].

    PubMed

    Alperovich, G; Idiarte, L; Besasso, O; Avagnina, A

    2003-01-01

    Ischemic colitis is a well-recognized complication occurring in renal transplant recipients. It has often been associated with cytomegalovirus (CMV) vasculitis. However, the diagnosis of this pathology in the absence of CMV suggests that other etiological factors might be involved. Drugs inducing mesenteric vasoconstriction, such as non-steroidal anti-inflamatory drugs (NSAIDs) and cyclosporine could be related to this entity.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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

  1. AOM/DSS Model of Colitis-Associated Cancer.

    PubMed

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.

  2. Topical therapy is underused in patients with ulcerative colitis.

    PubMed

    Seibold, F; Fournier, N; Beglinger, C; Mottet, C; Pittet, V; Rogler, G

    2014-01-01

    The availability of new topical preparations for the treatment of left sided ulcerative colitis offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in left-sided colitis as compared to a systemic therapy. Therefore, we were interested in the use of topical therapy in patients with ulcerative colitis. The key question was whether topical treatment is more frequently used than oral therapy in patients with proctitis and left sided colitis. Data of 800 patients of the Swiss IBD cohort study were analyzed. Sixteen percent of patients of the cohort had proctitis, 21% proctosigmoiditis and 41% pancolitis. Topical therapy with 5-ASA or corticosteroids was given in 26% of patients with proctitis, a combined systemic and topical treatment was given in 13%, whereas systemic treatment with 5-ASA without topical treatment was given in 29%. Proportion of topical drug use decreased with respect to disease extension from 39% for proctitis to 13.1% for pancolitis (P=0.001). Patients with severe colitis received a significantly higher dose of topical 5-ASA than patients in remission. Side effects of topical or systemic 5-ASA or budesonide treatment were less frequently seen compared to other medications. Topical treatment was frequently stopped over time. The quality of life was the same in patients with limited disease compared to patients with pancolitis. Topical treatment in proctitis patients was underused in Switzerland. Since topical treatment is safe and effective it should be used to a larger extend.

  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. 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.

  5. 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

  6. 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.

  7. 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

  8. Ulcerative colitis and rheumatoid arthritis: a rare association--case report.

    PubMed

    Cruz, Vitor Alves; Yamaguchi, Lúcio; Ribeiro, Carolina Nazeozeno; Magalhães, Vanessa de Oliveira; Rego, Jozelia; Silva, Nilzio Antonio da

    2012-08-01

    Ulcerative colitis is an autoimmune disorder of unknown etiology. Although the large intestine is the major focus of autoimmunity, resulting in chronic diarrhea, that is actually a systemic disease, with numerous extraintestinal manifestations, such as articular involvement. The frequent association of a number of autoimmune diseases in the same patient has been described. However, the coexistence of ulcerative colitis and rheumatoid arthritis is rare. The authors report a case of ulcerative colitis associated with rheumatoid arthritis, in which colitis occurred 12 years before the onset of inflammatory arthropathy.

  9. American ginseng suppresses inflammation and DNA damage associated with mouse colitis

    PubMed Central

    Jin, Yu; Kotakadi, Venkata S.; Ying, Lei; Cui, Xiangli; Wood, Patricia A.; Windust, Anthony; Matesic, Lydia E.; Pena, Edsel A.; Chiuzan, Codruta; Singh, Narendra P.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Wargovich, Michael J.; Hofseth, Lorne J.

    2008-01-01

    Ulcerative colitis (UC) is a dynamic, idiopathic, chronic inflammatory condition associated with a high colon cancer risk. American ginseng has antioxidant properties and targets many of the players in inflammation. The aim of this study was to test whether American ginseng extract prevents and treats colitis. Colitis in mice was induced by the presence of 1% dextran sulfate sodium (DSS) in the drinking water or by 1% oxazolone rectally. American ginseng extract was mixed in the chow at levels consistent with that currently consumed by humans as a supplement (75 p.p.m., equivalent to 58 mg daily). To test prevention of colitis, American ginseng extract was given prior to colitis induction. To test treatment of colitis, American ginseng extract was given after the onset of colitis. In vitro studies were performed to examine mechanisms. Results indicate that American ginseng extract not only prevents but it also treats colitis. Inducible nitric oxide synthase and cyclooxygenase-2 (markers of inflammation) and p53 (induced by inflammatory stress) are also downregulated by American ginseng. Mucosal and DNA damage associated with colitis is at least in part a result of an oxidative burst from overactive leukocytes. We therefore tested the hypothesis that American ginseng extract can inhibit leukocyte activation and subsequent epithelial cell DNA damage in vitro and in vivo. Results are consistent with this hypothesis. The use of American ginseng extract represents a novel therapeutic approach for the prevention and treatment of UC. PMID:18802031

  10. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    PubMed

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  11. [Ischemic colitis: an uncommon manifestation in systemic lupus erythematosus].

    PubMed

    Medina, Viviana; Bulgach, Valeria; Lagandara, Pamela; Berner, Enrique

    2013-04-01

    We present the case of an adolescent with ischemic colitis, an infrequent pathology in this age group, worsened in the presence of systemic lupus erythematosus (SLE). The patient, aged 20, was diagnosed SLE at 6. She consulted for fever, abdominal pain in the side and right iliac fossa and diarrhea lasting 48 hours. It was assumed as acute gastroenteritis but given the persistent pain, incoercible vomiting and abdominal distension she was hospitalized. The abdominal X-ray showed distended loops, abundant feces, without air-fluid levels. The ultrasound showed erosions and ulcerations, edema and bleeding in the descending colon submucosal layer. The CT scan evidenced an ischemic lesion in the right colon. Ischemic colitis is a severe condition, infrequent in young individuals. Signs, symptoms, abdominal CT scan and colonoscopy are the elements of choice for the diagnosis.

  12. [Ischemic colitis: an uncommon manifestation in systemic lupus erythematosus].

    PubMed

    Medina, Viviana; Bulgach, Valeria; Lagandara, Pamela; Berner, Enrique

    2013-04-01

    We present the case of an adolescent with ischemic colitis, an infrequent pathology in this age group, worsened in the presence of systemic lupus erythematosus (SLE). The patient, aged 20, was diagnosed SLE at 6. She consulted for fever, abdominal pain in the side and right iliac fossa and diarrhea lasting 48 hours. It was assumed as acute gastroenteritis but given the persistent pain, incoercible vomiting and abdominal distension she was hospitalized. The abdominal X-ray showed distended loops, abundant feces, without air-fluid levels. The ultrasound showed erosions and ulcerations, edema and bleeding in the descending colon submucosal layer. The CT scan evidenced an ischemic lesion in the right colon. Ischemic colitis is a severe condition, infrequent in young individuals. Signs, symptoms, abdominal CT scan and colonoscopy are the elements of choice for the diagnosis. PMID:23568076

  13. Pyoderma gangrenosum and ulcerative colitis in the tropics.

    PubMed

    Alese, Olatunji B; Irabor, David O

    2008-01-01

    Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.

  14. [Recent advances in medical and surgical treatment of ulcerative colitis].

    PubMed

    Sugita, Akira; Koganei, Kazutaka; Tatsumi, Kenji; Futatsuki, Ryo; Kuroki, Hirosuke; Yamada, Kyoko; Arai, Katsuhiko; Fukushima, Tsuneo

    2015-03-01

    Recent advances in both medical and surgical treatment of ulcerative colitis have been remarkable. Changes in medical treatment are mainly good results of therapy with the anti-TNF-α antibody, tacrolimus, and those in surgical treatment are an expansion of the surgical indications to include patients with intractable disease, such as treatment refractoriness and chronic corticosteroid dependence, by a better postoperative clinical course after pouch surgery, improred selection of surgical procedures and the timing of surgery in elderly patients. To offer the optimal treatment for patients with ulcerative colitis, new medical therapies should be analyzed from the standpoint of the efficacy and limitations of effect. Long postoperative clinical course of surgical patients including colitic cancer, prevention of postoperative complications should be also analyzed.

  15. 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

  16. Crucial role of macrophage selenoproteins in experimental colitis

    PubMed Central

    Kaushal, Naveen; Kudva, Avinash K.; Patterson, Andrew D.; Chiaro, Christopher; Kennett, Mary J.; Desai, Dhimant; Amin, Shantu; Carlson, Bradley A.; Cantorna, Margherita T.; Prabhu, K. Sandeep

    2014-01-01

    Inflammation is a hallmark of inflammatory bowel disease (IBD) that involves macrophages. Given the inverse link between selenium (Se) status and IBD-induced inflammation, our objective was to demonstrate that selenoproteins in macrophages were essential to suppress pro-inflammatory mediators, in part, by the modulation of arachidonic acid metabolism. Acute colitis was induced using 4% DSS in wild type mice maintained on Se-deficient (<0.01 ppm Se), Se-adequate (0.1 ppm; sodium selenite), and two supraphysiological levels in the form of Se-supplemented (0.4 ppm; sodium selenite) and high Se (1.0 ppm; sodium selenite) diets. Transfer RNASec (tRNA[sec]) knockout mice (Trspfl/flLysMCre) were used to examine the role of selenoproteins in macrophages on disease progression and severity using histopathological evaluation, expression of pro-inflammatory and anti-inflammatory genes, and modulation of prostaglandin (PG) metabolites in urine and plasma. While Se-deficient and Se-adequate mice showed increased colitis and exhibited poor survival, Se supplementation at 0.4 and 1.0 ppm increased survival of mice and decreased colitis-associated inflammation with an up-regulation of expression of pro-inflammatory and anti-inflammatory genes. Metabolomic profiling of urine suggested increased oxidation of PGE2 at supraphysiological levels of Se that also correlated well with Se-dependent upregulation of 15-hydroxy-PG dehydrogenase (15-PGDH) in macrophages. Pharmacological inhibition of 15-PGDH, lack of selenoprotein expression in macrophages, and depletion of infiltrating macrophages indicated that macrophage-specific selenoproteins and upregulation of 15-PGDH expression were key for Se-dependent anti-inflammatory and pro-resolving effects. Selenoproteins in macrophages protect mice from DSS-colitis by enhancing 15-PGDH-dependent oxidation of PGE2 to alleviate inflammation, suggesting a therapeutic role for Se in IBD. PMID:25187657

  17. 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

  18. Thrombin drives tumorigenesis in colitis-associated colon cancer

    PubMed Central

    Rosenfeldt, Leah; Kombrinck, Keith; Flick, Matthew J.; Steinbrecher, Kris A.; Harmel-Laws, Eleana; Mullins, Eric S.; Shaw, Maureen; Witte, David P.; Revenko, Alexey; Monia, Brett; Palumbo, Joseph S.

    2014-01-01

    The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. Based on evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/− mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacological inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC was temporally associated with the antecedent inflammatory colitis. However, direct studies of the antecedent colitis showed that mice carrying half-normal prothrombin levels were comparable to control mice in mucosal damage, inflammatory cell infiltration and associated local cytokine levels. These results suggest that thrombin supports early events coupled to inflammation-mediated tumorigenesis in CAC that are distinct from overall inflammation-induced tissue damage and inflammatory cell trafficking. That prothrombin is linked to early events in CAC was strongly inferred by the observation that prothrombin deficiency dramatically reduced the formation of very early, pre-cancerous aberrant crypt foci. Given the importance of inflammation in the development of colon cancer, these studies suggest that therapeutic interventions at the level of hemostatic factors may be an effective means to prevent and/or impede colitis-associated colon cancer progression. PMID:24710407

  19. 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

  20. 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

  1. AOM/DSS Model of Colitis-Associated Cancer.

    PubMed

    Parang, Bobak; Barrett, Caitlyn W; Williams, Christopher S

    2016-01-01

    Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer. PMID:27246042

  2. Invasive balantidiasis presented as chronic colitis and lung involvement.

    PubMed

    Ladas, S D; Savva, S; Frydas, A; Kaloviduris, A; Hatzioannou, J; Raptis, S

    1989-10-01

    A unique case of chronic balantidiasis is described, presenting with chronic colitis and inflammatory polyposis of the rectum and sigmoid colon and an intrapulmonary mass. Histology of the colonic polyps showed Balantidium coli, and both Aspergillus and Balantidium coli were found in the aspirate of the pulmonary mass. The patient was treated with doxycycline HCl 100 mg/day for 10 days with complete clinical recovery and marked improvement of the endoscopic appearance of the colonic mucosa. PMID:2791818

  3. Opposing roles of Prostaglandin D2 receptors in ulcerative colitis

    PubMed Central

    Sturm, Eva M.; Radnai, Balazs; Jandl, Katharina; Stančić, Angela; Parzmair, Gerald P.; Högenauer, Christoph; Kump, Patrizia; Wenzl, Heimo; Petritsch, Wolfgang; Pieber, Thomas R.; Schuligoi, Rufina; Marsche, Gunther; Ferreirós, Nerea; Heinemann, Akos; Schicho, Rudolf

    2014-01-01

    Pro-resolution functions were reported for Prostaglandin D2 (PGD2) in colitis, but the role of its two receptors, DP and in particular CRTH2 are less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes, and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of DSS colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared to control subjects. In contrast, CRTH2 was decreased in eosinophils, NK and CD3+ T cells but not in monocytes and CD3+/CD4+ T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydroTXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved while the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue where it may contribute to inflammation whereas DP likely promotes anti-inflammatory actions. PMID:24929001

  4. Quality of life in patients with ulcerative colitis treated surgically

    PubMed Central

    Kozłowska, Katarzyna A.; Krokowicz, Piotr

    2014-01-01

    Introduction Ulcerative colitis belongs to the group of inflammatory bowel diseases. The specific symptoms and chronic nature of the disease significantly affect the quality of patients’ lives. Quality-of-life assessment helps to define its determining factors as well as the efficiency of surgical procedures. Aim Quality-of-life evaluation of patients with ulcerative colitis treated surgically. Material and methods A retrospective review was carried out on 35 patients with ulcerative colitis, who were treated surgically in the Clinic of General and Colorectal Surgery, University of Medical Sciences in Poznan. The research tools used to assess the quality of life consisted of: the Inflammatory Bowel Disease Questionnaire, a Polish version of the Short Form Health Survey-36, and a questionnaire. Results The mean of the IBDQ scale was 152.51, and the median was 161. In this scale, a higher score indicates better quality of life. The situation in the subjective SF-36 scale is reversed: a lower score indicates better quality of life. The mean of the SF-36 was 115.94, and the median was 58. Many discrepancies in the field (e.g. the influence of determining factors) create a niche for further studies. Conclusions Moreover, quality-of-life evaluation may lead to better patient care, understanding their problems or treatment modifications, and finally may become a kind of therapy efficiency parameter. PMID:25276253

  5. Surgical treatment of ulcerative colitis in the biologic therapy era

    PubMed Central

    Biondi, Alberto; Zoccali, Marco; Costa, Stefano; Troci, Albert; Contessini-Avesani, Ettore; Fichera, Alessandro

    2012-01-01

    Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis, biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease. The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven. Furthermore, these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications. Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients. Surgery is traditionally recommended as salvage therapy when medical management fails, and, despite advances in medical therapy, colectomy rates remain unchanged between 20% and 30%. To overcome the reported increase in postoperative complications in patients on biologic therapies, several surgical strategies have been developed to maintain long-term pouch failure rate around 10%, as previously reported. Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field. PMID:22563165

  6. Surgical Management and Outcome in Acute Ischemic Colitis

    PubMed Central

    Beck, David E.; de Aguilar-Nascimento, Jose Eduardo

    2011-01-01

    Background Ischemic colitis is the most common form of gastrointestinal ischemia. Patients usually present with abdominal discomfort and bloody diarrhea. Treatment is contingent on the severity of disease. Mucosal/nongangrenous ischemia requires only supportive measures and medical management, whereas transmural/gangrenous ischemia may require prompt surgical intervention. The purpose of this study was to review the surgical management of ischemic colitis in a tertiary referral center. Methods Retrospective chart review of patients with ischemic colitis managed from 1995 to 2000 at the Ochsner Foundation Hospital. Results Forty-eight patients were identified. Ten of these had disease significant enough to require surgery (21%) and are the basis of this review. Eight were women, and the mean age was 71.4 years (range 43-85 years). Distribution of the disease was the right colon in 4 cases, pancolitis in 3, sigmoid in 2, and the left colon in 1. Nine patients underwent bowel resection: primary anastomosis in 3 and creation of a stoma in the other 6 (5 ileostomies and 1 transverse colostomy). Follow-up ranged from 3 days to 13.8 years. One patient died perioperatively. Conclusion Surgical management produced good results. PMID:21960763

  7. 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

  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. 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

  10. 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.

  11. Differential acute effects of selenomethionine and sodium selenite on the severity of colitis.

    PubMed

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

    2015-04-01

    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

  12. Role of Histologic Inflammation in the Natural History of Ulcerative Colitis.

    PubMed

    Patil, Deepa T; Moss, Alan C; Odze, Robert D

    2016-10-01

    The goals of therapy for ulcerative colitis have moved from symptom improvement to mucosal healing, and finally histologic resolution. The natural history of histologic inflammation in ulcerative colitis progresses from initial cellular infiltration to architectural disruption and recovery on medical therapy. Many studies have linked histologic changes to clinical outcomes, providing prognostic value to histologic abnormalities. This review covers all these components. PMID:27633592

  13. 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

  14. 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. PMID:27424097

  15. 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

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

    PubMed

    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. Fecal transplantation indications in ulcerative colitis. Preliminary study

    PubMed Central

    LASZLO, MIHAELA; CIOBANU, LIDIA; ANDREICA, VASILE; PASCU, OLIVIU

    2016-01-01

    Background and aims Fecal microbiota transplantation is used with success in persistent (more than two episodes) Clostridium Difficile Infection; it has also gained importance and started to be used in inflammatory bowel disease. There are theoretical arguments that justify its use in ulcerative colitis or Crohn’s disease. Based on our clinical cases we tried to evaluate the indications of fecal microbiota transplantation young patients with ulcerative colitis and multiple relapses, in which biological or immunosuppressive treatment were ineffective. Methods Five patients with moderate-severe ulcerative colitis or Clostridium Difficile infection who ceased to have a therapeutic response to biological therapy, were given fecal microbiota transplant as an alternative to biological therapy and/or immunosuppression. Fecal microbiota transplant was administered via colonoscopy using healthy donors from their family. Results The results were favorable and spectacular in all patients and complete remission was achieved for at least 10 months. Clinical remission was achieved in all patients. Endoscopic appearance of ulcers in patients improved. In 2 patients the effect of the fecal microbiota transplant diminished after 10–12 months and the tendency to relapse appeared (3–4 stools/day, blood streaks present sometimes in the stool). Reintroduction of systemic therapy or immunosuppression demonstrated that patients regained the therapeutic response to these treatments, and remission was maintained. Conclusion Fecal microbiota transplantation can be used as salvage therapy in patients refractory to biological therapy, as elective therapy in clostridium difficile infection or as an alternative therapy in young patients with multiple relapses who have reservations regarding biological or immunosuppressive treatment. PMID:27152073

  18. New Keys to Maintenance Treatment in Ulcerative Colitis

    PubMed Central

    Higgins, Peter D.R.

    2010-01-01

    Maintenance treatment in ulcerative colitis often fails to prevent flares and long term complications. The first key to maintenance is to use effective therapy, even when patients become asymptomatic. The second key is to communicate the importance of adherence to patients, and to help them achieve long term adherence. Simplified dosing schedules are of some benefit, but the bond between patient and doctor, and the patient's belief in the efficacy of the therapy are essential. Decreased co-pays (a fixed amount paid by patients seeking care that is not reimbursed my medical insurance) have been associated with increased adherence, and incentives for patients may be a cost-effective approach to improving adherence. While the most substantial data on the association between adherence and clinical outcomes is in 5-ASAs, non-adherence can also limit the efficacy of thiopurines and biologics. The third key to maintenance treatment is monitoring and maintaining control of inflammation. Decreased histologic and endoscopic damage to the colon has been associated with decreased risk of colon cancer. The most cost-effective way to monitor smoldering inflammation is not known, but endoscopy, structured symptom indices, and biomarkers may be valuable approaches. The fourth key to maintenance treatment is optimizing immunomodulator therapy with thiopurines, and possibly methotrexate in the future. The fifth key to maintenance treatment in ulcerative colitis is maintaining biologic efficacy by avoiding low trough levels and being vigilant for subclinical inflammation and symptom recurrence at the end of dose intervals. Combination therapy with immunomodulators improves trough levels in Crohn's, and may prove to have benefits for the maintenance of biologic efficacy in ulcerative colitis. PMID:20926876

  19. 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

  20. Clinical Characteristics of Ischemic Colitis According to Location

    PubMed Central

    Chang, Ho Jin; Chung, Chul Woon; Ko, Kwang Hyun

    2011-01-01

    Purpose The aim of this study was to analyze various clinical characteristics of ischemic colitis according to its location. Methods The medical records of 92 cases of gastrointestinal ischemic colitis (IC) diagnosed at Bundang CHA Hospital from 1995 to 2008 were reviewed and analyzed retrospectively. The patients were diagnosed by using colonoscopic biopsies or laparotomy findings. The patients were divided into two groups, right and left, according to the main involvement area of the IC at the embryologic boundary line of the distal transverse colon, and the two groups were compared as to clinical characteristics and co-morbid diseases. Results Left IC was present in 59 patients (64.1%) and right IC in 33 patients (35.9%). No differences between the two groups in terms of clinical characteristics, cardiovascular disease and diabetes mellitus were observed. However, in 16 cases with renal failure, 10 patient had right IC and 6 patients had left IC, and this difference had statistical significance (P = 0.014). Among the 16, the 11 patients requiring hemodialysis included 8 with right IC (24.2%) and 3 with left IC (5.1%; P = 0.009). Among the 19 cases of severe IC requiring surgical treatment or involving mortality, irrespective of surgery, 11 patients showed right IC and 8 patients showed left IC (P = 0.024). Conclusion Right-side ischemic colitis was significantly associated with renal failure and disease severity, so patients with right-side colon ischemia should be more carefully observed and managed. PMID:22259742

  1. Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis

    PubMed Central

    Suzuki, Kenji; Arumugam, Somasundaram; Yokoyama, Junji; Kawauchi, Yusuke; Honda, Yutaka; Sato, Hiroki; Aoyagi, Yutaka; Terai, Shuji; Okazaki, Kazuichi; Suzuki, Yasuo; Mizumoto, Shuji; Sugahara, Kazuyuki; Atreya, Raja; Neurath, Markus F.; Watanabe, Kenichi; Hashiguchi, Taishi; Yoneyama, Hiroyuki; Asakura, Hitoshi

    2016-01-01

    Induction of mucosal healing (MH) is an important treatment goal in inflammatory bowel disease (IBD). Although the molecular mechanisms underlying MH in IBD is not fully explored, local fibrosis would contribute to interfere mucosal repair. Carbohydrate sulfotransferase 15 (CHST15), which catalyzes sulfation of chondroitin sulfate to produce rare E-disaccharide units, is a novel mediator to create local fibrosis. Here we have used siRNA-based approach of silencing CHST15 in dextran sulfate sodium (DSS) induced colitis in mice, human colon fibroblasts and cancer cell lines. In a DSS-induced acute colitis model, CHST15 siRNA reduced CHST15 mRNA in the colon, serum IL-6, disease activity index (DAI) and accumulation of F4/80+ macrophages and ER-TR7+ fibroblasts, while increased Ki-67+ epithelial cells. In DSS-induced chronic colitis models, CHST15 siRNA reduced CHST15 mRNA in the colon, DAI, alpha-smooth muscle actin+ fibroblasts and collagen deposition, while enhanced MH as evidenced by reduced histological and endoscopic scores. We also found that endoscopic submucosal injection achieved effective pancolonic delivery of CHST15 siRNA in mice. In human CCD-18 Co cells, CHST15 siRNA inhibited the expression of CHST15 mRNA and selectively reduced E-units, a specific product biosynthesized by CHST15, in the culture supernatant. CHST15 siRNA significantly suppressed vimentin in both TGF-ß-stimulated CCD18-Co cells and HCT116 cells while up-regulated BMP7 and E-cadherin in HCT116 cells. The present study demonstrated that blockade CHST15 represses colonic fibrosis and enhances MH partly though reversing EMT pathway, illustrating a novel therapeutic opportunity to refractory and fibrotic lesions in IBD. PMID:27410685

  2. 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. PMID:20568987

  3. The Evaluation of Postoperative Patients with Ulcerative Colitis.

    PubMed

    Shen, Bo

    2016-10-01

    Restorative proctocolectomy with ileal pouch-anal anastomosis has become the standard surgical treatment modality for patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Normally staged pouch surgery is performed. Endoscopy plays an important role in postoperative monitoring of disease status and delivery of therapy, if necessary. Therefore, ileal pouch surgery significantly alters bowel anatomy, with new organ structures being created. Endoscopy of the altered bowel includes the evaluation of end ileostomy, Hartmann pouch or diverted rectum, loop ileostomy, diverted pouch, and pouchoscopy. Each segment of the bowel has unique landmarks. PMID:27633595

  4. Colitis cystica profunda of the rectum: An unexpected operative finding

    PubMed Central

    Ayantunde, Abraham A; Strauss, Claire; Sivakkolunthu, Malathi; Malhotra, Anu

    2016-01-01

    Colitis cystic profunda is a rare entity benign condition of the colon and rectum that can mimic suspicious polyps or malignancy. The commonest sites of affectation are the rectum and the sigmoid colon but it can be unusually widely distributed in the colon. The aetiology of this condition is not fully elucidated and confident diagnosis can only be made on histological features. We hereby describe a patient who presented with significant rectal symptoms and an unexpected finding of a submucosal mucous cyst mimicking a suspicious rectal polyp and highlighted its significance and the review of the literature. PMID:27458593

  5. Association of intestinal malignant lymphoma and ulcerative colitis.

    PubMed

    Watanabe, Naoko; Sugimoto, Naoshi; Matsushita, Akiko; Maeda, Akinori; Nagai, Kenichi; Hanioka, Keisuke; Takahashi, Takayuki

    2003-12-01

    A 42-year-old woman with refractory ulcerative colitis (UC) developed ascites, pleural effusion, pretibial edema and severe anemia. Colonofiberscopic examination showed a bulky submucosal tumor in the sigmoid colon, which was histologically diagnosed as malignant lymphoma (diffuse large, B cell type). The lymphoma was resistant to chemotherapy. Autologous peripheral blood stem cell transplantation (PBSCT) was effective; however, she died of severe infection after the second PBSCT. Although the association of intestinal lymphoma with UC is rare, lymphoma should be taken into consideration when the clinical course of UC is atypical or when UC is refractory to therapy.

  6. Fermented milk containing Lactobacillus GG alleviated DSS-induced colitis in mice and activated epidermal growth factor receptor and Akt signaling in intestinal epithelial cells.

    PubMed

    Yoda, Kazutoyo; He, Fang; Miyazawa, Kenji; Hiramatsu, Masaru; Yan, Fang

    2012-01-01

    Lactobacillus rhamnosus GG was assessed for its ability to alleviate DSS-induced colitis in mice and activate epidermal growth factor receptor and Akt signaling in intestinal epithelial cells. In this study mice were treated with DSS to induce colitis and they were given Lactobacillus GG fermented milk to assess the effect of probiotic on colitis. Lactobacillus GG fermented milk significantly reduced the colitis associated changes suggesting a protective effect against DSS induced colitis.

  7. 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

  8. Indeterminate colitis: a review of the concept--what's in a name?

    PubMed

    Geboes, Karel; Colombel, Jean-Frédéric; Greenstein, Adrian; Jewell, Derek P; Sandborn, William J; Vatn, Morten H; Warren, Bryan; Riddell, Robert H

    2008-06-01

    The precise diagnosis of colitis cannot always be established with the available diagnostic tools. The subgroup of patients with an uncertain diagnosis has been classified as "indeterminate colitis" (IC). The definition of "indeterminate," however, has changed over the years. Originally, IC was proposed by pathologists for colectomy specimens, usually from patients operated on for severe colitis, showing overlapping features of ulcerative colitis (UC) and Crohn's disease (CD). Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, and other features allowing a diagnosis of either UC or CD. Therefore, it is difficult to compare different studies. An International Organization of Inflammatory Bowel Diseases (IOIBD) working party confirmed 1) the ambiguous nature of the term, and 2) proposes an updated classification for the category of patients with an unclear diagnosis. According to this, the term IBD unclassified (IBDU) is confirmed, as suggested by the Montreal Working Party 2005 for patients with clinically chronic colitis, that clearly have IBD but when definitive features of CD or UC are absent. In resected specimens the term "colitis of uncertain type or etiology" (CUTE) is preferred. It is accepted that most of the time this may have a prefix, such as severe, chronic. The classification of IBD varies when based only on biopsies rather than on a colectomy specimen. The vast majority of these have severe colitis. For those that cannot bear to abandon the highly ambiguous term IC, if it is used at all, this is where it can be used parenthetically. PMID:18213696

  9. Caffeic acid ameliorates colitis in association with increased Akkermansia population in the gut microbiota of mice

    PubMed Central

    Zhang, Zhan; Wu, Xinyue; Cao, Shuyuan; Wang, Li; Wang, Di; Yang, Hui; Feng, Yiming; Wang, Shoulin; Li, Lei

    2016-01-01

    Emerging evidence shows that dietary agents and phytochemicals contribute to the prevention and treatment of ulcerative colitis (UC). We first reported the effects of dietary caffeic acid (CaA) on murine experimental colitis and on fecal microbiota. Colitis was induced in C57BL/6 mice by administration of 2.5% dextran sulfate sodium (DSS). Mice were fed a control diet or diet with CaA (1 mM). Our results showed that dietary CaA exerted anti-inflammatory effects in DSS colitis mice. Moreover, CaA could significantly suppress the secretion of IL-6, TNFα, and IFNγ and the colonic infiltration of CD3+ T cells, CD177+ neutrophils and F4/80+ macrophages via inhibition of the activation of NF-κB signaling pathway. Analysis of fecal microbiota showed that CaA could restore the reduction of richness and inhibit the increase of the ratio of Firmicute to Bacteroidetes in DSS colitis mice. And CaA could dramatically increase the proportion of the mucin-degrading bacterium Akkermansia in DSS colitis mice. Thus, CaA could ameliorate colonic pathology and inflammation in DSS colitis mice, and it might be associated with a proportional increase in Akkermansia. PMID:27177331

  10. Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens.

    PubMed

    Bábíčková, Janka; Tóthová, Ľubomíra; Lengyelová, Eva; Bartoňová, Anastázie; Hodosy, Július; Gardlík, Roman; Celec, Peter

    2015-10-01

    Sex differences have been found in the incidence and progression of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The reported differences in observational studies are controversial, and the effects of sex hormones on the pathogenesis of IBD are not clear. The aim of this study was to analyze sex differences in the progression of experimentally induced colitis. Experimental colitis was induced in adult mice by adding 2% dextran sodium sulfate (DSS) into drinking water. Male and female mice were used as intact, gonadectomized, and supplemented with either estradiol or testosterone. In comparison to males, female mice with induced colitis had significantly longer colon (p < 0.05), lower decrease in body weight (p < 0.001), and lower stool consistency score (p < 0.05). Histopathological analysis showed less inflammatory infiltrates (p < 0.001) and crypt damage (p < 0.001) in female mice. Female mice with colitis had also lower concentration of TNF-α in colon homogenates (p < 0.01). Supplementation with estradiol in ovariectomized mice ameliorated the severity of colitis. Female mice are partially protected against chemically induced colitis. This protection seems to be mediated by estradiol.

  11. 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

  12. 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

    2016-01-01

    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

  13. 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. PMID:27063801

  14. 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. PMID:25624746

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

    PubMed Central

    Lim, Su-Min; Choi, Hyun Sik; Jeong, Jin-Ju; Han, Seung-Won

    2016-01-01

    We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC). Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg) did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg) significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg) and DWac (15 mg/kg) additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine. PMID:27761147

  16. Targeting IL-12/IL-23 by Employing a p40 Peptide-Based Vaccine Ameliorates TNBS-Induced Acute and Chronic Murine Colitis

    PubMed Central

    Guan, Qingdong; Ma, Yanbing; Hillman, China-Li; Qing, Gefei; Ma, Allan G; Weiss, Carolyn R; Zhou, Gang; Bai, Aiping; Warrington, Richard J; Bernstein, Charles N; Peng, Zhikang

    2011-01-01

    Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn’s disease. Previously, we have developed and identified three mouse p40 peptide-based and virus-like particle vaccines. Here, we evaluated the effects and immune mechanisms of the optimal vaccine in downregulating intestinal inflammation in murine acute and chronic colitis, induced by intrarectal administrations of trinitrobenzene sulfonic acid (TNBS). Mice were injected subcutaneously with vaccine, vaccine carrier or saline three times, and then intrarectally administered TNBS weekly for 2 wks (acute colitis) or 7 wks (chronic colitis). The severity of colitis was evaluated by body weight, histology and collagen and cytokine levels in colon tissue. Th1 and Th17 cells in mesenteric lymph nodes (MLN) were determined. Our results showed the vaccine induced high level and long-lasting specific IgG antibodies to p40, IL-12 and IL-23. After administrations of TNBS, vaccinated mice had significantly less body weight loss and a significant decrease of inflammatory scores, collagen deposition and expression of p40, IL-12, IL-23, IL-17, TNF, iNOS and Bcl-2 in colon tissues, compared with carrier and saline groups. Moreover, vaccinated mice exhibited a trend to lower percentages of Th1 cells in acute colitis and of Th17 cells in chronic colitis in MLN than in controls. In summary, administration of the vaccine induced specific antibodies to IL-12 and IL-23, which was associated with improvement of intestinal inflammation and fibrosis. This suggests that the vaccine may provide a potential approach for the long-term treatment of Crohn’s disease. PMID:21424108

  17. [Ulcerative colitis in Taichung Veterans General Hospital: a clinical study].

    PubMed

    Chang, L M; Ho, K S; Chen, G H

    1995-11-01

    This report concerns 34 patients of ulcerative colitis admitted to Taichung Veterans General Hospital, from 1983 to 1994. Among them 26 were male and 8 were female. The age at onset were mostly from 50 to 60. The average duration between onset of symptoms and the date of definite diagnosis was 10 months. The most common presenting symptom was bloody diarrhea (64.7%). Most of our patients were in the moderately severe group of disease (67.6%), according to the severity defined by Truelove and Witts. The most frequent endoscopic findings of mucosa was classified as Grade III (38.2). Descending colon (91.2), rectum (85.3%), and sigmoid colon (88.2%) were the most frequently involved areas. The major clinical course were chronic intermittent and chronic continuous type (55.9%). Extraintestinal manifestations were found in 2 cases: one was found in the skin, and the other in the joint, respectively. Treatment of ulcerative colitis in our series was mainly medical (91.2%). However, 3 patients received emergent surgical intervention, and 10 patients finally underwent operation because of major complications or failure to respond to medical treatment.

  18. 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

  19. A case of reactive arthritis due to Clostridium difficile colitis.

    PubMed

    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

  20. Epithelial ER Stress in Crohn's Disease and Ulcerative Colitis.

    PubMed

    Cao, Stewart S

    2016-04-01

    Research in the past decade has greatly expanded our understanding of the pathogenesis of inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. In addition to the sophisticated network of immune response, the epithelial layer lining the mucosa has emerged as an essential player in the development and persistence of intestinal inflammation. As the frontline of numerous environmental insults in the gut, the intestinal epithelial cells are subject to various cellular stresses. In eukaryotic cells, disturbance of endoplasmic reticulum homeostasis may lead to the accumulation of unfolded and misfolded proteins in the ER lumen, a condition called ER stress. This cellular process activates the unfolded protein response, which functions to enhance the ER protein folding capacity, alleviates the burden of protein synthesis and maturation, and activates ER-associated protein degradation. Paneth and goblet cells, 2 secretory epithelial populations in the gut, are particularly sensitive to ER stress on environmental or genetic disturbances. Recent studies suggested that epithelial ER stress may contribute to the pathogenesis of Crohn's disease and ulcerative colitis by compromising protein secretion, inducing epithelial cell apoptosis and activating proinflammatory response in the gut. Our knowledge of ER stress in intestinal epithelial function may open avenue to new inflammatory bowel disease therapies by targeting the ER protein folding homeostasis in the cells lining the intestinal mucosa.

  1. Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis.

    PubMed Central

    Connell, W R; Talbot, I C; Harpaz, N; Britto, N; Wilkinson, K H; Kamm, M A; Lennard-Jones, J E

    1994-01-01

    This study examined three features associated with colorectal carcinoma complicating ulcerative colitis: (a) the distribution of 157 cancers in 120 patients with ulcerative colitis treated at St Mark's Hospital between 1947 and 1992; (b) the frequency at which dysplasia was found at a distance from the tumour in 50 total proctocolectomy specimens in which an average of 27 histology blocks were reviewed, and (c) the five year survival rate according to Dukes's stage and participation in a surveillance programme. Of 157 carcinomas, 88 (56%) occurred in the rectosigmoid, 19 (12%) in the descending colon or splenic flexure, and 50 (32%) in the proximal colon. Among the 120 patients, the rectum or sigmoid colon contained cancer in 81 (67.5%). Dysplasia was detected in 41 of 50 reviewed proctocolectomy specimens (82%). Dysplasia distant to a malignancy occurred in 37 (74%); two were classified indefinite, probably positive, 19 were low grade, and 16 were high grade; in 18 specimens there was an elevated dysplastic lesion. Survival was related to the Dukes's stage: about 90% of patients with Dukes's A or B cancer were alive at five years. The five year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p = 0.024). PMID:7959198

  2. 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

  3. 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

  4. Negative regulation of DSS-induced experimental colitis by PILRα.

    PubMed

    Kishida, Kazuki; Kohyama, Masako; Kurashima, Yosuke; Kogure, Yuta; Wang, Jing; Hirayasu, Kouyuki; Suenaga, Tadahiro; Kiyono, Hiroshi; Kunisawa, Jun; Arase, Hisashi

    2015-06-01

    Inflammatory bowel disease is thought to be a complex multifactorial disease, in which an increased inflammatory response plays an important role. Paired immunoglobulin-like type 2 receptor α (PILRα), well conserved in almost all mammals, is an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domain. PILRα is mainly expressed on myeloid cells and plays an important role in the regulation of inflammation. In the present study, we investigated the function of PILRα in inflammatory bowel disease using PILRα-deficient mice. When mice were orally administered dextran sulfate sodium (DSS), colonic mucosal injury and inflammation were significantly exacerbated in DSS-treated PILRα-deficient mice compared with wild-type (WT) mice. Flow cytometric analysis revealed that neutrophil and macrophage cell numbers were higher in the colons of DSS-treated PILRα-deficient mice than in those of WT mice. Blockade of CXCR2 expressed on neutrophils using a CXCR2 inhibitor decreased the severity of colitis observed in PILRα-deficient mice. These results suggest that PILRα negatively regulates inflammatory colitis by regulating the infiltration of inflammatory cells such as neutrophils and macrophages.

  5. Fulminant ulcerative colitis in a healthy pregnant woman.

    PubMed

    Orabona, Rossana; Valcamonico, Adriana; Salemme, Marianna; Manenti, Stefania; Tiberio, Guido A M; Frusca, Tiziana

    2015-05-21

    This case report concerns a 25-year-old patient with 6-7 bloody stools/d, abdominal pain, tachycardia, and weight loss occurring during the third trimester of pregnancy. Severe ulcerative colitis complicated by toxic megacolon and gravidic sepsis was diagnosed by clinical evaluation, colonoscopy, and rectal biopsy that were performed safely without risk for the mother or baby. The patient underwent a cesarean section at 28+6 wk gestation. The baby was transferred to the neonatal intensive care unit of our hospital and survived without complications. Fulminant colitis was managed conservatively by combined colonoscopic decompression and medical treatment. Although current European guidelines describe toxic megacolon as an indication for emergency surgery for both pregnant and non-pregnant women, thanks to careful monitoring, endoscopic decompression, and intensive medical therapy with nutritional support, we prevented the woman from having to undergo emergency pancolectomy. Our report seems to suggest that conservative management may be a helpful tool in preventing pancolectomy if the patient's condition improves quickly. Otherwise, surgery is mandatory. PMID:26019473

  6. [Association between ulcerative colitis and primary esclerosing cholangitis].

    PubMed

    Aguilar Sanchez, Victor; Guzman Rojas, Patricia; Bravo Paredes, Eduar; Rios Perez, Cristian

    2016-01-01

    Ulcerative Colitis (UC) is associated to Primary Sclerosing Cholangitis (PSC) in 80% of cases, and this association is more common than the one with Crohn’s disease. Nevertheless, the prevalence of PSC in patients with UC is only 2.9% in Latin America. We present the case of a female patient who presents a clinical history characterized for chronic diarrhea of one year of evolution, associated to fever, oral ulcers and loss of weight. In the laboratory results there is an elevation in the following: alkaline phosphatase, GGT, ALT and AST, for that reason we decide to do an abdominal ultrasound finding a hepatomegaly. In the colonoscopy we found an ulcerative colitis. Later, we do a magnetic resonance cholangiopancreatography, because of the diagnosis of UC and the abnormalities at the liver function tests, diagnosing PSC associated to UC. At that moment, the patient starts treatment with sulfasalazine that is stopped because of an adverse effect, starting prednisone and azathioprine. The patient then is discharged with the medication already mentioned and has a favorable clinical outcome. We decide to report the case because is the second reported case in Peru, being this association not commonly found in the South hemispheric. PMID:27409097

  7. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis

    PubMed Central

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I. Metin; Sutcu, Recep

    2016-01-01

    Background/Aims: 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). Methods: 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. Results: 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). Conclusions: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD. PMID:27539446

  8. 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

  9. Diffuse colorectal angiodysplasia misdiagnosed preoperatively as ulcerative colitis in a child: report of a case.

    PubMed

    Ozer, Ilter; Birol Bostanci, E; Ozogul, Yusuf B; Ulker, Aysel; Temucin, Tulay; Akoglu, Musa

    2008-01-01

    Angiodysplasia is primarily a disease of the elderly, and it is rarely encountered in the pediatric population. We report a case of diffuse colorectal angiodysplasia, diagnosed postoperatively in a 13-year-old boy who underwent hand-assisted laparoscopic total proctocolectomy and ileal pouch anal anastomosis (IPAA) for assumed corticosteroid-resistant ulcerative colitis. The findings of preoperative repeated colonoscopies and biopsies had been consistent with active colitis. Distinguishing ulcerative colitis from angiodysplasia is not usually difficult in patients with rectal bleeding. To our knowledge, this is the fi rst case report of such a challenging diagnostic problem. PMID:18668317

  10. 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

  11. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis

    PubMed Central

    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.

    2016-01-01

    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. PMID:26837003

  12. /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.

  13. Chest pain in a 12-year-old girl with ulcerative colitis after therapy with mesalazine

    PubMed Central

    Mukherjee, Nirajan; Pandya, Nikila; Bhaduri, Bim; Bala, K

    2013-01-01

    This case of chest pain complicating therapy received for ulcerative colitis in a young patient highlights the importance of a thorough history and clinical examination. The complication can be rapidly fatal if not recognised and treated quickly. PMID:23761603

  14. 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

    2016-01-01

    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. PMID:26837003

  15. [Mild spontaneous course of a case of pseudomembranous colitis. Case report and literature review].

    PubMed

    Jaeger, A; Wüst, J; Lüthy, R; Nüesch, H J; Munzinger, J

    1981-03-01

    Pseudomembranous colitis (PMC) caused by a toxin produced by Clostridium difficile is described in the literature as a severe diarrheal disease with a high mortality rate. A case which tends to absolve PMC from this reputation is reported involving an outpatient who developed well documented PMC subsequent to ampicillin therapy but required no treatment. The number of unreported cases of antibiotic-associated colitis with and without pseudomembrane formation is probably very high, since only severe cases of diarrhea are thoroughly investigated. In a chronological literature review an attempt is made to update the nomenclature of antibiotic-associated colitis. There are recent reports of a connection between the Clostridium difficile toxin and the chronic inflammatory "non-bacterial" intestinal diseases ulcerative colitis and Crohn's disease. The authors finally consider whether in cases of antibiotic-associated diarrhea efforts should be made to isolate Clostridium difficile and/or demonstrate the presence of its toxin, for the purposes of prognosis and therapy.

  16. Successful use of adalimumab in patient with treatment-refractory microscopic colitis.

    PubMed

    Anderson, Rebecca Jane; Makins, Richard

    2016-01-01

    A 50-year-old woman with treatment-refractory lymphocytic colitis was diagnosed with ankylosing spondylitis. She was started on adalimumab injections which significantly improved her stool frequency and consistency and, consequently, her quality of life. PMID:27530873

  17. [Clostridium difficile and cytomegalovirus involved in a case of pseudomembranous colitis].

    PubMed

    García, Coralith; Velarde, Juan; Cedron, Hugo; Ferrufino, Juan Carlos; Seas, Carlos; Bussalleu, Alejandro; Gotuzzo, E; Gotuzzo, Eduardo

    2007-01-01

    We report an unusual case of pseudomembranous colitis with fatal outcome where C. difficile and cytomegalovirus coexistense in a Peruvian patient with AIDS and gastrointestinal compromise by a mycobacterium.

  18. Corticosteroids in the Treatment of Pseudomembranous Colitis: A Report of 3 Cases

    PubMed Central

    Sykes, Ella; McDonald, Patrick; Flanagan, Paul K.

    2012-01-01

    Clostridium difficile associated diarrhoea has been an increasing problem in the last decade in the UK and is a cause of significant morbidity. At the most severe end of the spectrum it causes pseudomembranous colitis which has a significant associated mortality rate and can be refractory to standard treatments. Here we present three cases of proven pseudomembranous colitis in which systemic corticosteroids were used as an adjunct to treatment, raising the possibility of a new treatment option for this difficult condition.

  19. New Zealand Society of Gastroenterology Guidelines for the Management of Refractory Ulcerative Colitis.

    PubMed

    Eliadou, Elena; Day, Andrew S; Thompson-Fawcett, Mark W; Gearry, Richard B; Rowbotham, David S; Walmsley, Russel; Schultz, Michael; Inns, Stephen J

    2015-10-16

    The management of patients with ulcerative colitis who are dependent on corticosteroid for control of symptoms, or refractory to corticosteroids or standard immunosuppressive therapy, is challenging. The development of newer medical therapies has increased the options for managing patients in this situation, but access and funding remain limited. This guideline summarises the literature regarding this situation and provides guidance as to the management of refractory colitis in the New Zealand setting. PMID:26645757

  20. Induction of IDO-1 by immunostimulatory DNA limits severity of experimental colitis.

    PubMed

    Ciorba, Matthew A; Bettonville, Ellen E; McDonald, Keely G; Metz, Richard; Prendergast, George C; Newberry, Rodney D; Stenson, William F

    2010-04-01

    The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human inflammatory bowel disease and in experimental models of colitis, there is an increased expression of the enzyme IDO. IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine trinitrobenzene sulfonic acid model of colitis, inhibition of this enzyme leads to worsened disease severity, suggesting that IDO acts as a natural break in limiting colitis. In this investigation, we show that induction of IDO-1 by a TLR-9 agonist, immunostimulatory (ISS) DNA, critically contributes to its colitis limiting capacities. ISS DNA induces intestinal expression of IDO-1 but not the recently described paralog enzyme IDO-2. This induction occurred in both epithelial cells and in subsets of CD11c(+) and CD11b(+) cells of the lamina propria, which also increase after ISS-oligodeoxynucleotide. Signaling required for intestinal IDO-1 induction involves IFN-dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the trinitrobenzene sulfonic acid and dextran sodium sulfate models of colitis, we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histological correlates of colitis in these models were improved by administration of the TLR-9 agonist; however, when the function of IDO is inhibited, the colitis limiting effects of ISS-oligodeoxynucleotide were abrogated. These findings support the possibility that targeted induction of IDO-1 is an approach deserving further investigation as a therapeutic strategy for diseases of intestinal inflammation.

  1. Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis

    PubMed Central

    Andersson, Christina; Kvist, Peter H.; McElhinney, Kathryn; Baylis, Richard; Gram, Luise K.; Pelzer, Hermann; Lauritzen, Brian; Holm, Thomas L.; Hogan, Simon; Wu, David; Turpin, Brian; Miller, Whitney; Palumbo, Joseph S.

    2015-01-01

    The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage. PMID:26098308

  2. 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.

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

    PubMed

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

    2011-10-01

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

  4. Pseudomembranous colitis: report of a severe case with unusual clinical signs in a young nurse.

    PubMed

    Boaz, A; Dan, M; Charuzi, I; Landau, O; Aloni, Y; Kyzer, S

    2000-02-01

    We describe the case of a young and otherwise healthy nurse who developed pseudomembranous colitis ten days after receiving oral clindamycin for dental infection. Her clinical course was particularly stormy and was characterized by severe diarrhea and vomiting, profuse ascites, pleural effusion, abdominal tenderness, peritoneal irritation, and systemic toxicity. The Clostridium difficile assay was negative on two occasions. Features compatible with pseudomembranous colitis were seen at sigmoidoscopy, and the diagnosis was confirmed by biopsies. PMID:10696903

  5. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

    PubMed

    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  6. Effect of venlafaxine on experimental colitis in normal and reserpinised depressed rats

    PubMed Central

    Minaiyan, Mohsen; Hajhashemi, Valiollah; Rabbani, Mohammad; Fattahian, Ehsan; Mahzouni, Parvin

    2015-01-01

    Psychological disorders such as depression have more prevalence in inflammatory bowel disease patients and can exacerbate the clinical course of the disease, so anti-depressant therapy may have a potential to positively impact the disease course. On the other hand several antidepressant drugs have shown anti-inflammatory and immunomodulatory properties. Thus, this study aimed to explore the beneficial effects of venlafaxine on experimental colitis in normal and reserpinised depressed rats. Acetic acid colitis was induced in both reserpinised and non-reserpinised rats. Reserpinised groups received reserpine at dose of 6 mg/kg i.p.1 h prior to colitis induction and then treated with venlafaxine at doses of 10, 20, 40 mg/kg given i.p. 2 h after induction of colitis and daily for 4 consecutive days. Non-reserpinised groups treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic, histological and myeloperoxidase activity measurements. Results showed that reserpine at dose of 6 mg/kg exacerbated the colitis damage. Compared to acetic acid control, venlafaxine at dose of 40 mg/kg as well as dexamethasone significantly improved colitis parameters in both reserpinised and non-reserpinised animals. Venlafaxine reduced inflammatory injury in this animal model of induced ulcerative colitis. These effects are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug. PMID:26600857

  7. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons.

    PubMed

    Lv, Qi; Qiao, Si-miao; Xia, Ying; Shi, Can; Xia, Yu-feng; Chou, Gui-xin; Wang, Zheng-tao; Dai, Yue; Wei, Zhi-feng

    2015-12-01

    Norisoboldine (NOR), the main active constituent of Radix Linderae, was previously demonstrated to ameliorate collagen-induced arthritis in rats through regulating the imbalance of T cells in intestines, which implied its therapeutic potential in inflammatory bowel disease. Here, we investigated the effect of NOR on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. Results showed that NOR (20, 40mg/kg) markedly reduced the symptoms of colitis, the levels of IL-1β and TNF-α, and the activation of ERK, p38 MAPK and NF-κB-p65. NOR only slightly decreased the levels of IFN-γ and IL-17A in mouse colons, but it dramatically increased the level of IL-10 at both protein and mRNA grades. Consistently, NOR increased the number of CD4(+)CD25(+)Foxp3(+) Treg cells more obviously than it decreased that of CD4(+)IL-17(+) Th17 cells in mesenteric lymph nodes (MLNs) and colonic lamina proprias (LPs) of colitis mice, and promoted the expression of Foxp3 mRNA in colon tissues. It could facilitate the in vitro differentiation of Treg cells from naive T cells and promote the phosphorylations of Smad2/3 in colon tissues of colitis mice. On the other hand, NOR did not affect the expressions of homing receptors CCR9 and α4β7 in SPs, and homing ligands CCL25 and Madcam-1 in MLNs and colonic LPs, suggesting that the increase of Treg cells in colons by NOR was not due to gut homing. In conclusion, NOR can ameliorate DSS-induced UC in mice, and the mechanisms involve reduction of pro-inflammatory cytokines and selective induction of Treg cells in colons.

  8. 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.

  9. 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

  10. 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

  11. [Hepatobiliary diseases in Crohn disease and ulcerative colitis].

    PubMed

    Kruis, W

    1987-02-01

    Hepatobiliary diseases are certainly not very frequent extraintestinal complications of chronic intestinal inflammatory diseases, however, they are an important prognostic factor. 2% of patients with ulcerative colitis develop liver cirrhosis but 10% of those die as a direct result of liver failure. Other associated severe hepatobiliary diseases include primary sclerosing cholangitis, carcinoma of the bile duct and amyloidosis. The present review attempts to divide the associated hepatobiliary diseases into three groups. 1. those that are the result of therapy. 2. those that are the result of the pathophysiological mechanisms of the underlying disease and 3. those of unknown etiological origin. This division might serve not only for a better understanding of the various mechanisms but should have some impact on therapeutic regimens.

  12. The role of bacteria in the pathogenesis of ulcerative colitis.

    PubMed

    Sasaki, Maiko; Klapproth, Jan-Michael A

    2012-01-01

    Factors implicated in the pathophysiology of ulcerative colitis (UC) are an abnormal immune response, defect in intestinal epithelial barrier function, and gut microbiota. Currently, it is unclear whether specific bacterial strains are responsible for the induction of intestinal inflammation, but increased bacterial tissue invasion has been described in affected UC patients. Further, a quantitative and qualitative microbial imbalance in UC, defined as dysbiosis, has been characterized by an increase in Rhodococcus spp., Shigella spp., and Escherichia spp., but a decrease in certain Bacteroides spp.. More specifically, Campylobacter spp., Enterobacteriae, and enterohepatic Helicobacter were more prevalent in tissue sample from UC patients subjected to molecular detection methods, but not controls. In addition, serologic testing identified Fusobacterim varium as a potential contributor to the intestinal inflammation in UC. Interestingly, in-situ hybridization studies have shown anti-inflammatory Lactobacillus spp. and Pediococcus spp. were absent in samples from subjects affected by UC. Therefore, dysbiosis is a factor in the pathogenesis of UC. PMID:22619714

  13. Cerebral venous sinus thrombosis as presenting feature of ulcerative colitis.

    PubMed

    Ennaifer, R; Moussa, A; Mouelhi, L; Salem, M; Bouzaidi, S; Debbeche, R; Trabelsi, S; Najjar, T

    2009-01-01

    Thrombosis is a well recognized complication of inflammatory bowel disease that occurs in 1.3 to 6.4% of patients, however, cerebral vascular involvement is unusual. We present the case of a 16-year-old female in whom cerebral venous thrombosis was the presenting symptom of an active ulcerative pancolitis. Thrombophilia screen (plasma levels of proteins C and S, antithrombin, antibeta2-glycoprotein, lupus anticoagulant and anticardiolipin antibodies, activated protein C resistance, homocystein level antinuclear antibodies) was negative. The patient was successfully treated with anticoagulant therapy, phenobarbital and sulfasalazine. Cerebral venous thrombosis is an exceptional presenting feature of ulcerative colitis. Disease activity may play a major role in the occurrence of thrombosis. PMID:19902870

  14. Severe tracheobronchial stenosis and bronchiectasis complicating ulcerative colitis.

    PubMed

    Suzuki, Toshio; Tsushima, Kenji; Sakairi, Yuichi; Yoshida, Shigetoshi; Yoshino, Ichiro; Tatsumi, Koichiro

    2014-03-01

    A 37-year-old woman with a 20-year history of ulcerative colitis (UC) was admitted with complaints of cough and increasing sputum production. Chest computed tomography showed severe stenosis of the left main bronchus and bronchiectasis of the left lower lobe. Biopsy specimens from the area of bronchial stenosis showed chronic inflammation with lymphocyte infiltration, and we diagnosed respiratory involvement of UC. The bronchial stenosis was successfully treated with yttrium aluminum garnet (YAG) laser. UC is a systemic illness with occasional extraintestinal manifestations, but upper airway involvement is rare, and to our knowledge, this is the first published report of UC complicated with bronchopulmonary lesions with successful YAG laser treatment of the main bronchial stenosis. PMID:25473563

  15. A rare case of ulcerative colitis exacerbated by VZV infection.

    PubMed

    Nishimura, Satoshi; Yoshino, Takuya; Fujikawa, Yoshiki; Watanabe, Masaki; Yazumi, Shujiro

    2015-12-01

    A 16-years old man with severe ulcerative colitis (UC) was admitted to our hospital. After initiating treatment with corticosteroid for UC, chicken pox appeared. At the same time of appearance of chicken pox, the disease activity of UC was exacerbated. After initiating the treatment with acyclovir, both chicken pox and UC improved. Because colonoscopic findings revealed the remaining of moderately active UC, initiating the treatment with infliximab could induce clinical remission of UC without relapse of varicella-zoster virus (VZV) infection. This is a very rare case of UC with concomitant VZV infection. According to our report, the vaccination for VZV prior to immunosuppressive treatments would be necessary for VZV naïve patients with UC. PMID:26552918

  16. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

    PubMed Central

    Schnell, Dan; Krzeski, Piotr; Abreu, Maria T; Altman, Douglas G; Colombel, Jean-Frédéric; Feagan, Brian G; Hanauer, Stephen B; Lémann, Marc; Lichtenstein, Gary R; Marteau, Phillippe R; Reinisch, Walter; Sands, Bruce E; Yacyshyn, Bruce R; Bernhardt, Christian A; Mary, Jean-Yves; Sandborn, William J

    2011-01-01

    Background Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC). Objective To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated. Design A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0–11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0–100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors. Results There was 76% agreement for ‘severe’, but 27% agreement for ‘normal’ appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR2, Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity). Conclusion The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall

  17. Ulcerative Colitis and Its Association with Salmonella Species.

    PubMed

    Tripathi, Manish Kumar; Pratap, Chandra Bhan; Dixit, Vinod K; Singh, Tej Bali; Shukla, Sunit K; Jain, Ashok K; Nath, Gopal

    2016-01-01

    Ulcerative colitis (UC) is characterized by presence of ulcer in colon and bloody diarrhea. The present study explores the possibility of association between Salmonella and ulcerative colitis. The present study comprised 59 cases of UC, 28 of colon cancer (CC), 127 of irritable bowel syndrome (IBS), and 190 of healthy control. The serological study was done by Widal and Indirect Haemagglutination Assay (IHA) for ViAb. Nested PCR was performed targeting fliC, staA, and stkG gene for Typhi and Paratyphi A, respectively. A total of 15.3% patients were positive for Salmonella "O" antigen among them 18.6% UC, 35.5% CC, 12.6% IBS, and 15.3% healthy control. A total of 36.9% patients were positive for "H" antigen including 39.0%, 57.1%, and 67.7% UC, CC, and IBS, respectively. About 1.73% show positive agglutination for AH antigen including 3.4%, 3.6%, and 1.6%, UC, CC, and IBS. A total of 10.89% were positive for ViAb. While 6.8% of UC, 10.7% of CC, 11.0% of IBS, and 12.1% of healthy subjects were positive for the antibody, the PCR positivity rates for Salmonella specific sequences were 79.7% in UC, 53.6% in CC, 66.1% in IBS, and 16.3% in healthy controls. The present study suggested that higher prevalence of Salmonella might play important role in etiopathogenesis of UC, IBS, and CC. PMID:26904116

  18. Hand-assisted laparoscopic restorative proctocolectomy for ulcerative colitis

    PubMed Central

    Shimada, Norimitsu; Ohge, Hiroki; Yano, Raita; Murao, Naoki; Shigemoto, Norifumi; Uegami, Shinnosuke; Watadani, Yusuke; Uemura, Kenichiro; Murakami, Yoshiaki; Sueda, Taijiro

    2016-01-01

    AIM To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy (HALS-RP) compared with the conventional open procedure (OPEN-RP). METHODS Fifty-one patients who underwent restorative total proctocolectomy with rectal mucosectomy and ileal pouch anal anastomosis between January 2008 and July 2015 were retrospectively analyzed. Twenty-three patients in the HALS-RP group and twenty-four patients in the OPEN-RP group were compared. Four patients who had purely laparoscopic surgery were excluded. Restorative total proctocolectomy was performed with mucosectomy and a hand-sewn ileal-pouch-anal anastomosis. Preoperative comorbidities, intraoperative factors such as blood loss and operative time, postoperative complications, and postoperative course were compared between two groups. RESULTS Patients in both groups were matched with regards to patient age, gender, and American Society of Anesthesiologists score. There were no significant differences in extent of colitis, indications for surgery, preoperative comorbidities, and preoperative medications in the two groups. The median operative time for the HALS-RP group was 369 (320-420) min, slightly longer than the OPEN-RP group at 355 (318-421) min; this was not statistically significant. Blood loss was significantly less in HALS-RP [300 (230-402) mL] compared to OPEN-RP [512 (401-1162) mL, P = 0.003]. Anastomotic leakage was noted in 3 patients in the HALS-RP group and 2 patients in the OPEN-RP group (13% vs 8.3%, NS). The rates of other postoperative complications and the length of hospital stay were not different between the two groups. CONCLUSION HALS-RP can be performed with less blood loss and smaller skin incisions. This procedure is a feasible technique for total proctocolectomy for ulcerative colitis. PMID:27648162

  19. 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.

  20. In vivo measurement of colonic butyrate metabolism in patients with quiescent ulcerative colitis

    PubMed Central

    Simpson, E; Chapman, M; Dawson, J; Berry, D; Macdonald, I; Cole, A

    2000-01-01

    BACKGROUND—Butyrate, a short chain fatty acid produced by bacterial fermentation, is a major fuel source for the colonocyte. In vitro work has shown that ulcerative colitis may be characterised by a metabolic defect in colonocyte butyrate oxidation.
AIMS—To investigate the rate of metabolism of rectally administered butyrate in patients with quiescent colitis.
METHODS—[1-13C]-butyrate enemas were administered to 11 patients with long standing quiescent ulcerative colitis and to 10 control patients. The rate of production of 13CO2 in exhaled breath over four hours was measured by isotope ratio mass spectrometry combined with indirect calorimetry in order to measure CO2 production. This allowed calculation of the patients' resting energy expenditure and respiratory quotient.
RESULTS—Over a four hour period, 325 (SEM 21) µmol 13CO2 was recovered in breath samples from the colitis group compared with 322 (17) µmol from the control group (NS). The respiratory quotient of the colitic group was significantly lower than that of the control group.
CONCLUSION—There was no difference in the rate of metabolism of butyrate between the two groups. It is unlikely that there is a primary metabolic defect of butyrate metabolism in patients with quiescent ulcerative colitis.


Keywords: ulcerative colitis; in vivo butyrate metabolism PMID:10601058

  1. 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

  2. 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

  3. 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

  4. 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

  5. Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis

    PubMed Central

    Arriola, Edurne; Wheater, Matthew; Lopez, Maria Antonette; Thomas, Gareth; Ottensmeier, Christian

    2016-01-01

    ABSTRACT Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8+, FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison. In eight cases (four on steroids only, four on steroids and infliximab), we evaluated two sequential biopsies. We observed that CD8+, FoxP3+, and GzmB T cell counts were significantly higher in patients with ipilimumab-related colitis compared to normal colon (p < 0.0001). Patients who required infliximab for the resolution of their colitis had a significantly higher CD8+/FoxP3 ratio than those treated only with steroids and this correlated with clinical severity. The analysis of repeat samples revealed that resolution of the colitis was associated with a decrease in CD8+ and FoxP3+ cells both in patients treated with steroids and infliximab. Our data suggest that counts of cytotoxic T cells and Tregs in the colonic mucosa from patients with ipilimumab-related colitis correlate with clinical findings and may predict severity and guide management.

  6. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice.

    PubMed

    Wang, Yungang; Tian, Jie; Tang, Xinyi; Rui, Ke; Tian, Xinyu; Ma, Jie; Ma, Bin; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-03-29

    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.

  7. Ulcerative colitis and Crohn's disease: is Mycobacterium avium subspecies paratuberculosis the common villain?

    PubMed Central

    2010-01-01

    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. PMID:21167058

  8. Intestinal Microbiota Signatures Associated with Inflammation History in Mice Experiencing Recurring Colitis

    PubMed Central

    Berry, David; Kuzyk, Orest; Rauch, Isabella; Heider, Susanne; Schwab, Clarissa; Hainzl, Eva; Decker, Thomas; Müller, Mathias; Strobl, Birgit; Schleper, Christa; Urich, Tim; Wagner, Michael; Kenner, Lukas; Loy, Alexander

    2015-01-01

    Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history. PMID:26697002

  9. Vitamin A Inhibits Development of Dextran Sulfate Sodium-Induced Colitis and Colon Cancer in a Mouse Model

    PubMed Central

    Okayasu, Isao; Hana, Kiyomi; Nemoto, Noriko; Yoshida, Tsutomu; Saegusa, Makoto; Yokota-Nakatsuma, Aya; Song, Si-Young; Iwata, Makoto

    2016-01-01

    Vitamin A is essential to mucosal immunity and cell differentiation. The fact that lack of it might involve chronic inflammation and increased risk of cancer has been reported. Little is known about the mechanism of vitamin A deficiency in the development of colitis and its influence on development of colorectal cancer. To determine the influence of vitamin A deficiency on colitis and colorectal cancer development, an experimental study using a colitis mouse model was performed. Dextran sulfate sodium (DSS) colitis was induced in vitamin A-deficient and vitamin A-supplemented mice. Further, colorectal carcinoma was induced by a combination of azoxymethane preinjection and DSS colitis. Results were compared between the two groups mainly by immunohistochemical analysis. Colitis was more severe and recovery from colitis was slower in vitamin A-deficient mice than in vitamin A-supplemented mice. Compared with vitamin A-supplemented mice, vitamin A-deficient mice had decreases in colonic subepithelial myofibroblasts and the ratio of mucosal IgA+/IgG+ cells, increases in CD11c+ dendritic cells, and a higher rate of development of colorectal carcinoma with colitis following azoxymethane. Vitamin A lipid droplets in subepithelial myofibroblasts were decreased in vitamin A-deficient mice, suggesting alterations in colonic crypt niche function. Thus, vitamin A inhibited colitis and the development of colorectal cancer. PMID:27298823

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Nagy-Szakal, Dorottya; Mir, Sabina A. V.; Harris, R. Alan; Dowd, Scot E.; Yamada, Takeshi; Lacorazza, H. Daniel; Tatevian, Nina; Smith, C. Wayne; de Zoeten, Edwin F.; Klein, John; Kellermayer, Richard

    2015-01-01

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5+ CD4+ T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.—Nagy-Szakal, D., Mir, S. A. V., Harris, R. A., Dowd, S. E., Yamada, T., Lacorazza, H. D., Tatevian, N., Smith, C. W., de Zoeten, E. F., Klein, J., Kellermayer, R. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis. PMID:25903104

  12. Non-Hematopoietic β-Arrestin1 Confers Protection Against Experimental Colitis.

    PubMed

    Lee, Taehyung; Lee, Eunhee; Arrollo, David; Lucas, Peter C; Parameswaran, Narayanan

    2016-05-01

    β-Arrestins are multifunctional scaffolding proteins that modulate G protein-coupled receptor (GPCR)-dependent and -independent cell signaling pathways in various types of cells. We recently demonstrated that β-arrestin1 (β-arr1) deficiency strikingly attenuates dextran sodium sulfate (DSS)-induced colitis in mice. Since DSS-induced colitis is in part dependent on gut epithelial injury, we examined the role of β-arr1 in intestinal epithelial cells (IECs) using a colon epithelial cell line, SW480 cells. Surprisingly, we found that knockdown of β-arr1 in SW480 cells enhanced epithelial cell death via a caspase-3-dependent process. To understand the in vivo relevance and potential cell type-specific role of β-arr1 in colitis development, we generated bone marrow chimeras with β-arr1 deficiency in either the hematopoietic or non-hematopoietic compartment. Reconstituted chimeric mice were then subjected to DSS-induced colitis. Similar to our previous findings, β-arr1 deficiency in the hematopoietic compartment protected mice from DSS-induced colitis. However, consistent with the role of β-arr1 in epithelial apoptosis in vitro, non-hematopoietic β-arr1 deficiency led to an exacerbated colitis phenotype. To further understand signaling mechanisms, we examined the effect of β-arr1 on TNF-α-mediated NFκB and MAPK pathways. Our results demonstrate that β-arr1 has a critical role in modulating ERK, JNK and p38 MAPK pathways mediated by TNF-α in IECs. Together, our results show that β-arr1-dependent signaling in hematopoietic and non-hematopoietic cells differentially regulates colitis pathogenesis and further demonstrates that β-arr1 in epithelial cells inhibits TNF-α-induced cell death pathways.

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

    SciTech Connect

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

    2010-11-12

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

  14. FTY720 ameliorates oxazolone colitis in mice by directly affecting T helper type 2 functions.

    PubMed

    Daniel, Carolin; Sartory, Nico A; Zahn, Nadine; Schmidt, Ronald; Geisslinger, Gerd; Radeke, Heinfried H; Stein, Jurgen M

    2007-07-01

    The sphingosine-1-phosphate analogue FTY720 is known to alter migration and homing of lymphocytes via sphingosine-1-phosphate receptors. However, several studies indicate that its mode of action is more complex and that FTY720 may also directly influence cytokine effector functions. Therefore, we studied the effect of FTY720 in T helper type (Th2)-mediated oxazolone-induced colitis in mice. Following rectal oxazolone instillation, Th2 cells producing IL-13 induce a progressive colitis resembling human ulcerative colitis. A rectal enema of oxazolone [90 mg/kg body weight] was applied to BALB/c mice. FTY720 was administered i.p. from day 0 to 3 or from day 3 to 5 following the instillation of the haptenating agent. Assessment of severity of colitis was performed daily. FTY720 plasma levels were detected using LC-MS/MS-analysis. Colon tissue was analyzed macroscopically and microscopically, myeloperoxidase activity as well as cytokine levels of lamina propria CD4(+) T-cells and T1/ST2 expression were determined. Treatment with FTY720 prominently reduced the clinical and histopathologic severity of oxazolone-induced colitis, abrogating body weight loss, diarrhea, and macroscopic and microscopic intestinal inflammation. The therapeutic effects of FTY720 were associated with a prominent reduction of the key effector Th2 cytokines IL-13, IL-4 and IL-5. Strikingly, FTY720 inhibited GATA3 and T1/ST2 expression which represent highly relevant markers for Th2 differentiation and Th2 effector function, respectively. Our data provide the first evidence that FTY720 exhibits beneficial prophylactic as well as therapeutic effects in Th2-mediated experimental colitis by directly affecting Th2 cytokine profiles probably by reducing T1/ST2, thus offering a new auspicious therapeutic instrument for the treatment of human ulcerative colitis.

  15. Endoscopic and histological features of mycophenolate mofetil colitis in patients after solid organ transplantation

    PubMed Central

    Calmet, Fernando H.; Yarur, Andres J.; Pukazhendhi, Geetha; Ahmad, Jawad; Bhamidimarri, Kalyan R.

    2015-01-01

    Background Mycophenolate mofetil (MMF) is an immunosuppressive agent commonly used after organ transplantation. Gastrointestinal side effects occur in approximately 45% of patients. The spectrum of histologic features associated with MMF colitis has been well described, but data on the endoscopic features is lacking. The aim of the study was to describe the endoscopic features of MMF colitis in solid organ transplant recipients (SOTRs) as well as the frequency of histologic features and identify associated risk factors. Methods A retrospective review of all SOTRs taking MMF and who underwent colonoscopy between 2000 and 2010 was performed. 36 cases of MMF colitis were identified and 361 patients served as controls. Descriptive statistics and data analysis looking for associated risk factors were performed. Results Among SOTRs taking MMF who underwent colonoscopy, MMF colitis was diagnosed in 9%. Endoscopic findings ranged from erythema (33%) to erosions/ulcers (19%). 47% of patients had a normal colonoscopy and everyone had rectal sparing. Histological findings included acute colitis-like findings (50%), inflammatory bowel disease-like characteristics (36%), ischemia-like findings (5.6%), and graft-versus-host disease-like features (8.3%). Diarrhea occurred in 83%. Kidney transplantation was associated with a higher risk of MMF colitis (OR 5.8 [2.86-11.86], P<0.0001) whereas liver transplantation was associated with a lower risk (OR 0.06 [0.03-0.16], P<0.0001). Conclusion MMF colitis is fairly prevalent in SOTRs taking MMF who undergo colonoscopy. Diarrhea is the most common reason for colonoscopy referral (83%) and up to 47% of patients have normal colonoscopy, suggesting the need for routine biopsies to help confirm the diagnosis. PMID:26126799

  16. An in vitro model to evaluate the impact of the soluble factors from the colonic mucosa of collagenous colitis patients on T cells: enhanced production of IL-17A and IL-10 from peripheral CD4⁺ T cells.

    PubMed

    Kumawat, Ashok Kumar; Nyhlin, Nils; Wickbom, Anna; Tysk, Curt; Bohr, Johan; Hultgren, Olof; Hörnquist, Elisabeth Hultgren

    2014-01-01

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1β and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines.

  17. Auto-Antibodies and Their Association with Clinical Findings in Women Diagnosed with Microscopic Colitis

    PubMed Central

    Ohlsson, Bodil

    2013-01-01

    Background Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. Methods and Findings Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59–67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. Conclusions Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC. PMID:23776613

  18. Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice

    PubMed Central

    Luo, Yang; Wu, Xiaotong; Ma, Zhuang; Tan, Weifeng; Wang, Lanlan; Na, Daxiang; Zhang, Guoying; Yin, Ang; Huang, He; Xia, Dan; Zhang, Yingmei; Shi, Xueying; Wang, Lu

    2016-01-01

    Inflammatory bowel disease (IBD) is an important factor in the induction of colon cancer, but its mechanism is unclear. Colitis and colitis-associated colorectal cancer (CAC) models induced using both dextran sulfate sodium (DSS) and the azoxymethane/DSS protocol were established in wild-type (WT) and CTRP4 transgenic (CTRP4-tg) C57BL6/J mice. Body weight, stool consistency and the presence of blood in the stool were analyzed; tumor quantity, size and histological characteristics were analyzed during the development of CAC. The CTRP4-tg mice exhibited significantly reduced colitis and developed far fewer macroscopic tumors; these tumors were smaller in size, and a majority of the colon tumors in these mice were restricted to the superficial mucosa. Tumors of lower grades were observed in the CTRP4-tg mice. Interleukin-6 was markedly downregulated in the CTRP4-tg mice during CAC tumorigenesis. The phosphorylation of ERK, signal transducer and activator of transcription 3 and Akt in the colon and the proliferation of intestinal epithelial cells were decreased in the CTRP4-tg mice. The injection of recombinant CTRP4 protein significantly reduced the colitis symptoms of the WT mice. CTRP4 plays an important role in inflammation and inflammation-associated colon tumorigenesis, and our research may provide a novel method for the treatment of IBD and CAC. PMID:27086950

  19. Local chemerin levels are positively associated with DSS-induced colitis but constitutive loss of CMKLR1 does not protect against development of colitis.

    PubMed

    Dranse, Helen J; Rourke, Jillian L; Stadnyk, Andrew W; Sinal, Christopher J

    2015-08-01

    Inflammatory bowel disease (IBD) is a family of disorders including ulcerative colitis and Crohn's disease that are characterized by chronic and relapsing intestinal inflammation. Increased production of proinflammatory mediators, possibly combined with low expression of anti-inflammatory mediators, is thought to promote the development and progression of IBD. In the current study, we demonstrate that expression, secretion, and processing of chemerin, a potent chemoattractant for cells expressing chemokine-like receptor 1 (CMKLR1), increased in the cecum and colon along a gradient positively associated with the severity of inflammation in dextran sodium sulfate (DSS)-induced colitis. We also show that levels of circulating bioactive chemerin increased following DSS treatment. At both 6-8 and 14-16 weeks of age, CMKLR1 knockout mice developed signs of clinical illness more slowly than wild type and had changes in circulating cytokine levels, increased spleen weight, and increased local chemerin secretion following DSS treatment. However, knockout mice ultimately developed similar levels of clinical illness and local inflammation as wild type. Finally, contrary to previous reports, intraperitoneal injection of bioactive chemerin had no effect on the severity of DSS-induced colitis. This suggests that local chemerin levels have a greater impact than circulating levels in the pathogenesis of colitis. Considered altogether, bioactive chemerin represents a novel biomarker for IBD severity, although strategies to modulate endogenous chemerin signaling other than chronic CMKLR1 loss are necessary in order to exploit chemerin as a therapeutic target for the treatment of IBD.

  20. Risk factors associated with the development of ischemic colitis

    PubMed Central

    Fernández, Joaquín Cubiella; Calvo, Luisa Núñez; Vázquez, Elvira González; García, Maria Jesús García; Pérez, Maria Teresa Alves; Silva, Isabel Martínez; Seara, Javier Fernández

    2010-01-01

    AIM: To ascertain the role of cardiovascular risk factors, cardiovascular diseases, standard treatments and other diseases in the development of ischemic colitis (IC). METHODS: A retrospective, case-control study was designed, using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003. IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible histology. Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy, excluding those with diagnosis of colitis. Cases were matched with controls (ratio 1:2), by age and sex. A conditional logistic regression was performed. RESULTS: A total of 483 patients (161 cases, 322 controls) were included; mean age 75.67 ± 10.03 years, 55.9% women. The principal indications for colonoscopy in the control group were lower gastrointestinal hemorrhage (35.4%), anemia (33.9%), abdominal pain (19.9%) and diarrhea (9.6%). The endoscopic findings in this group were hemorrhoids (25.5%), diverticular disease (30.4%), polyps (19.9%) and colorectal cancer (10.2%). The following variables were associated with IC in the univariate analysis: arterial hypertension (P = 0.033); dyslipidemia (P < 0.001); diabetes mellitus (P = 0.025); peripheral arterial disease (P = 0.004); heart failure (P = 0.026); treatment with hypotensive drugs (P = 0.023); angiotensin-converting enzyme inhibitors; (P = 0.018); calcium channel antagonists (P = 0.028); and acetylsalicylic acid (ASA) (P < 0.001). Finally, the following variables were independently associated with the development of IC: diabetes mellitus [odds ratio (OR) 1.76, 95% confidence interval (CI): 1.001-3.077, P = 0.046]; dyslipidemia (OR 2.12, 95% CI: 1.26-3.57, P = 0.004); heart failure (OR 3.17, 95% CI: 1.31-7.68, P = 0.01); peripheral arterial disease (OR 4.1, 95% CI: 1.32-12.72, P = 0.015); treatment with digoxin (digitalis) (OR 0.27, 95% CI: 0.084-0.857, P

  1. Anti-fibrogenic effects of the anti-microbial peptide cathelicidin in murine colitis-associated fibrosis

    PubMed Central

    Yoo, Jun Hwan; Ho, Samantha; Tran, Deanna Hoang-Yen; Cheng, Michelle; Bakirtzi, Kyriaki; Kukota, Yuzu; Ichikawa, Ryan; Su, Bowei; Tran, Diana Hoang-Ngoc; Hing, Tressia C.; Chang, Irene; Shih, David Q; Issacson, Richard E.; Gallo, Richard L.; Fiocchi, Claudio; Pothoulakis, Charalabos; Koon, Hon Wai

    2015-01-01

    Background and Aims Cathelicidin (LL-37 in human and mCRAMP in mice) represents a family of endogenous antimicrobial peptides with anti-inflammatory effects. LL-37 also suppresses collagen synthesis, an important fibrotic response, in dermal fibroblasts. Here we determined whether exogenous cathelicidin administration modulates intestinal fibrosis in two animal models of intestinal inflammation and in human colonic fibroblasts. Methods C57BL/6J mice (n=6 per group) were administered intracolonically with a trinitrobenzene sulphonic acid (TNBS) enema to induce chronic (6–7 weeks) colitis with fibrosis. mCRAMP peptide (5 mg/kg every 3 day, week 5–7) or cathelicidin gene (Camp)-expressing lentivirus (107 infectious units week 4) were administered intracolonically or intravenously, respectively. 129Sv/J mice were infected with Salmonella typhimurium orally to induce cecal inflammation with fibrosis. Camp expressing lentivirus (107 infectious units day 11) was administered intravenously. Results TNBS-induced chronic colitis was associated with increased colonic collagen (col1a2) mRNA expression. Intracolonic cathelicidin (mCRAMP peptide) administration or intravenous delivery of lentivirus-overexpressing cathelicidin gene significantly reduced colonic col1a2 mRNA expression in TNBS-exposed mice, compared to vehicle administration. Salmonella infection also caused increased cecal inflammation associated with collagen (col1a2) mRNA expression that was prevented by intravenous delivery of Camp-expressing lentivirus. Exposure of human primary intestinal fibroblasts and human colonic CCD-18Co fibroblasts to transforming growth factor-beta1 (TGF-beta1) and/or insulin-like growth factor 1 induced collagen protein and mRNA expression, that was reduced by LL-37 (3–5 µM) through a MAP kinase-dependent mechanism. Conclusion Cathelicidin can reverse intestinal fibrosis by directly inhibiting collagen synthesis in colonic fibroblasts. PMID:25729764

  2. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    PubMed

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  3. Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis.

    PubMed

    Viana-Cardoso, K V; Silva, M T B; Peixoto-Junior, A A; Marinho, L S; Matias, N S; Soares, P M G; Santos, A A; Brito, G A C; Rola, F H; Gondim, F de A A

    2015-04-01

    Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 μg kg(-1) (total of 600 μg kg(-1) ) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length(-1) ratio) and the Morris' score in TNBS-treated rats, it did not alter the colitis area and even lowered the Morris' score in MO-treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.

  4. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    PubMed

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  5. Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis.

    PubMed

    Sreedhar, Remya; Arumugam, Somasundaram; Karuppagounder, Vengadeshprabhu; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Harima, Meilei; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-12-01

    Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti-inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1β, IL-2Rα, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis.

  6. Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium-induced colitis in mice.

    PubMed

    Lin, Yan; Lin, Lianjie; Wang, Qiushi; Jin, Yu; Zhang, Ying; Cao, Yong; Zheng, Changqing

    2015-01-01

    Ulcerative colitis is a major form of inflammatory bowel disease and increases the risk of the development of colorectal carcinoma. The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) make them promising tools for treating immune-mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSC has hampered the use of bone marrow and umbilical cord blood derived MSC in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly-derived umbilical MSC (UMSC) on dextran sulfate sodium-induced colitis in mice. The severity of colitis in mice was assessed using bodyweight loss, stool consistency, rectal bleeding, colon shortening and haematological parameters. Colonic myeloperoxidase and pro-inflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 and inducible nitric oxide synthase in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly-derived UMSC significantly diminished the severity of colitis, reduced histolopathological score, and decreased myeloperoxidase activity and cytokines levels. Furthermore, the UMSC markedly decreased the expression of cyclooxygenase 2and inducible nitric oxide synthase in the colon. In addition, transplantation of UMSC reduced intestinal permeability and upregulated the expression of tight junction proteins. These results show that the anti-inflammation and regulation of tight junction proteins by Wharton's jelly-derived UMSC ameliorates colitis.

  7. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    PubMed

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

  8. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

    PubMed

    Cabrera, Sandra; Fernández, Alvaro F; Mariño, Guillermo; Aguirre, Alina; Suárez, María F; Español, Yaiza; Vega, José A; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M Soledad; Freije, José M P; Kroemer, Guido; López-Otín, Carlos

    2013-08-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

  9. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

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

    PubMed Central

    Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-01-01

    This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. PMID:27058552

  11. Prospective evaluation of upper gastrointestinal mucosal lesions in children with ulcerative colitis and Crohn's disease.

    PubMed

    Ruuska, T; Vaajalahti, P; Arajärvi, P; Mäki, M

    1994-08-01

    Eighty-eight consecutive children with inflammatory bowel disease were studied, and upper gastrointestinal endoscopy was performed in 80 of them as one of the initial investigations before commencing medical or nutritional treatment. Forty-one children were found to have Crohn's disease and 47, ulcerative colitis. Upper gastrointestinal endoscopy revealed pathology in 32 (80%) cases of Crohn's disease, esophagitis in 16, and esophageal ulcer in two, nonspecific gastritis in 22, duodenitis or duodenal ulcer in 18, and Helicobacter pylori infection in two cases. Granulomas were detected in 10 patients in the upper gastrointestinal tract: one esophageal, eight gastric, and three duodenal. Of the ulcerative colitis patients, seven had esophagitis, one had esophageal ulcer, 17 had nonspecific gastritis, two had gastric ulcers, two had duodenal ulcers, and five had H. pylori infection; altogether 30 (75%) yielded pathological findings. Radiological studies using barium meal revealed pathology in only eight of all inflammatory bowel disease cases. Symptoms at admission were not conclusive for definite diagnosis because 63% of patients with Crohn's disease had signs of colitis (such as diarrhea, bloody diarrhea) compared to 94% of ulcerative colitis patients. Upper gastrointestinal endoscopy may be used to achieve a specific diagnosis, thus being helpful when planning treatment. Also a considerable incidence of nonspecific gastritis, duodenitis, and esophagitis with or without concomitant H. pylori infection may be anticipated in children suffering from both ulcerative colitis and Crohn's disease.

  12. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

    PubMed Central

    Cabrera, Sandra; Fernández, Álvaro F.; Mariño, Guillermo; Aguirre, Alina; Suárez, María F.; Español, Yaiza; Vega, José A.; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M. Soledad; Freije, José M.P.; Kroemer, Guido; López-Otín, Carlos

    2013-01-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. PMID:23782979

  13. Sequestering HMGB1 via DNA-conjugated beads ameliorates murine colitis.

    PubMed

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

    2014-01-01

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

  14. Paeonol attenuates TNBS-induced colitis by inhibiting NF-{kappa}B and STAT1 transactivation

    SciTech Connect

    Ishiguro, Kazuhiro . E-mail: kio@med.nagoya-u.ac.jp; Ando, Takafumi; Maeda, Osamu; Hasegawa, Motofusa; Kadomatsu, Kenji; Ohmiya, Naoki; Niwa, Yasumasa; Xavier, Ramnik; Goto, Hidemi

    2006-11-15

    Paeonol, a major phenolic component of Moutan Cortex, is known to have anti-inflammatory activity. However, the effect of Paeonol on colitis has not been evaluated and the molecular mechanism of its anti-inflammatory action remains unknown. The aim of this study was to determine if Paeonol enema attenuates trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. We also investigated the effects of Paeonol in colon cancer-derived CW-2 cells and T cell leukemia-derived Jurkat cells treated with tumor necrosis factor {alpha} (TNF{alpha}) and/or interferon {gamma} (IFN{gamma}), which play critical roles in TNBS-induced colitis. Paeonol enema attenuated TNBS-induced colitis judging by body weigh reduction, colon length and histological score. Myeloperoxidase activity and inducible nitric oxide synthase (iNOS) production in the colon were also reduced with Paeonol enema. In CW-2 cells, Paeonol inhibited iNOS protein and mRNA expression induced by costimulation of TNF{alpha} and IFN{gamma}. Furthermore, Paeonol reduced TNF{alpha}-induced NF-{kappa}B transactivation and IFN{gamma}-induced STAT1 transactivation in CW-2 cells and also in Jurkat cells. These findings suggest that Paeonol enema may be useful for the treatment of colitis.

  15. Induction of ulcerative colitis in mice influences the course of infection with the nematode Trichuris muris.

    PubMed

    Vegas-Sánchez, M C; Rollán-Landeras, E; García-Rodríguez, J J; Bolás-Fernández, F

    2015-09-01

    The aim of this study was to assess the effect of infection with the nematode whipworm Trichuris muris on the course of chemically induced acute ulcerative colitis in CBA/J mice, a strain proven to be highly resistant to infection with T. muris. Each mouse was infected with 50 embryonated eggs of T. muris by oral gavage. Acute colitis was triggered by administering 4% dextran sulphate sodium (DSS) in the drinking water for nine consecutive days at different times after infection. Concurrent infection and DSS administration exacerbate the severity of the colitis while favouring the permanence of parasites in the intestine. The induction of ulcerative colitis from days 54 to 62 post-infection (p.i.), when all worms had been expelled, ameliorated the course of the inflammatory disease. When ulcerative colitis was triggered earlier on, from days 27 to 35 p.i., the beneficial effects on inflammatory events were clearly shown with signs of mucosal epithelization and regeneration as early as day 1 after DSS administration. Previous infections by T. muris therefore accelerate recovery from subsequently induced inflammatory bowel disease and such an effect assists the nematode to persist in the intestinal niche.

  16. The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL-6.

    PubMed

    Choi, J S; Kim, K-H; Lau, L F

    2015-11-01

    The matricellular protein CCN1 (CYR61) is known to function in wound healing and is upregulated in colons of patients with Crohn's disease and ulcerative colitis, yet its specific role in colitis is unknown. Here we have used Ccn1(dm/dm) knockin mice expressing a CCN1 mutant unable to bind integrins α6β1 and αMβ2 as a model to probe CCN1 function in dextran sodium sulfate (DSS)-induced colitis. Ccn1(dm/dm) mice exhibited high mortality, impaired mucosal healing, and diminished interleukin-6 (IL-6) expression during the repair phase of DSS-induced colitis compared with wild-type mice, despite having comparable severity of initial inflammation and tissue injury. CCN1-induced IL-6 expression in macrophages through integrin αMβ2 and in fibroblasts through α6β1, and IL-6 promoted intestinal epithelial cell (IEC) proliferation. Administration of purified CCN1 protein fully rescued Ccn1(dm/dm) mice from DSS-induced mortality, restored IEC proliferation and enhanced mucosal healing, whereas delivery of IL-6 partially rectified these defects. CCN1 therapy accelerated mucosal healing and recovery from DSS-induced colitis even in wild-type mice. These findings reveal a critical role for CCN1 in restoring mucosal homeostasis after intestinal injury in part through integrin-mediated induction of IL-6 expression, and suggest a therapeutic potential for activating the CCN1/IL-6 axis for treating inflammatory bowel disease.

  17. Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

    PubMed

    Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

    2013-10-01

    Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed. PMID:24063406

  18. Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis.

    PubMed

    Ziogas, Dimitrios C; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M; Najarian, Robert M; Nagel, Jutta M; Flier, Sarah N; Popov, Yury; Tseng, Yu-Hua; Kokkotou, Efi

    2013-05-15

    Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in α-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-β on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD. PMID:23538494

  19. Heligmosomoides polygyrus bakeri infection activates colonic FoxP3+ T cells enhancing their capacity to prevent colitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like Heligmosomoides bakeri (Hpb) can induce Tregs. Experiments explored if Hpb infection could protect mice from colitis through activation of colonic Treg and exam...

  20. Histologic remission: the ultimate therapeutic goal in ulcerative colitis?

    PubMed

    Peyrin-Biroulet, Laurent; Bressenot, Aude; Kampman, Wendy

    2014-06-01

    Ulcerative colitis (UC) is a disease of the mucosal layer, and activity of the disease is assumed to be related to mucosal appearance. Mucosal healing has emerged as a major therapeutic goal in UC. Whether mucosal healing should be the ultimate therapeutic goal in these patients is unknown. Even when endoscopy suggests mucosal healing, evidence of histologic activity has been observed. Histologic healing requires complete recovery of the colonic mucosa, with absence of inflammation or structural changes. Histologic improvements have been linked with improved clinical outcomes, such as a reduced risk of relapse and need for surgery/hospitalization and a reduced risk of developing cancer. Hence, there is a rationale for aiming for histologic remission in UC. Numerous methods of classification of histologic activity in UC have been proposed, although only some of these are widely used. We review the current definitions of histologic remission, the range of scoring systems most commonly used, and the evidence of histologic improvement that is available from the latest therapies for UC. We also highlight questions that will require careful consideration if histologic remission is to become more widely used as an end point in clinical trials and a treatment goal in clinical practice. PMID:23911875

  1. Colitis-associated colon cancer: Is it in your genes?

    PubMed Central

    Van Der Kraak, Lauren; Gros, Philippe; Beauchemin, Nicole

    2015-01-01

    Colitis-associated colorectal cancer (CA-CRC) is the cause of death in 10%-15% of inflammatory bowel disease (IBD) patients. CA-CRC results from the accumulation of mutations in intestinal epithelial cells and progresses through a well-characterized inflammation to dysplasia to carcinoma sequence. Quantitative estimates of overall CA-CRC risks are highly variable ranging from 2% to 40% depending on IBD severity, duration and location, with IBD duration being the most significant risk factor associated with CA-CRC development. Recently, studies have identified IBD patients with similar patterns of colonic inflammation, but that differ with respect to CA-CRC development, suggesting a role for additional non-inflammatory risk factors in CA-CRC development. One suggestion is that select IBD patients carry polymorphisms in various low penetrance disease susceptibility genes, which pre-dispose them to CA-CRC development, although these loci have proven difficult to identify in human genome-wide association studies. Mouse models of CA-CRC have provided a viable alternative for the discovery, validation and study of individual genes in CA-CRC pathology. In this review, we summarize the current CA-CRC literature with a strong focus on genetic pre-disposition and highlight an emerging role for mouse models in the search for CA-CRC risk alleles. PMID:26556996

  2. Comparative activities of milk components in reversing chronic colitis.

    PubMed

    Kanwar, J R; Kanwar, R K; Stathopoulos, S; Haggarty, N W; MacGibbon, A K H; Palmano, K P; Roy, K; Rowan, A; Krissansen, G W

    2016-04-01

    Inflammatory bowel disease (IBD) is a poorly understood chronic immune disorder for which there is no medical cure. Milk and colostrum are rich sources of bioactives with immunomodulatory properties. Here we compared the therapeutic effects of oral delivery of bovine milk-derived iron-saturated lactoferrin (Fe-bLF), angiogenin, osteopontin (OPN), colostrum whey protein, Modulen IBD (Nestle Healthsciences, Rhodes, Australia), and cis-9,trans-11 conjugated linoleic acid (CLA)-enriched milk fat in a mouse model of dextran sulfate-induced colitis. The CLA-enriched milk fat significantly increased mouse body weights after 24d of treatment, reduced epithelium damage, and downregulated the expression of proinflammatory cytokines and nitrous oxide. Modulen IBD most effectively decreased the clinical score at d 12, and Modulen IBD and OPN most effectively lowered the inflammatory score. Myeloperoxidase activity that denotes neutrophil infiltration was significantly lower in mice fed Modulen IBD, OPN, angiogenin, and Fe-bLF. A significant decrease in the numbers of T cells, natural killer cells, dendritic cells, and a significant decrease in cytokine expression were observed in mice fed the treatment diets compared with dextran sulfate administered mice. The Fe-bLF, CLA-enriched milk fat, and Modulen IBD inhibited intestinal angiogenesis. In summary, each of the milk components attenuated IBD in mice, but with differing effectiveness against specific disease parameters. PMID:26805965

  3. An isoform of ZBP-89 predisposes the colon to colitis

    PubMed Central

    Law, David J.; Labut, Edwin M.; Adams, Rachael D.; Merchant, Juanita L.

    2006-01-01

    Alternative splicing enables expression of functionally diverse protein isoforms. The structural and functional complexity of zinc-finger transcription factor ZBP-89 suggests that it may be among the class of alternatively spliced genes. We identified a human ZBP-89 splice isoform (ZBP-89ΔN), which lacks amino terminal residues 1–127 of the full-length protein (ZBP-89FL). ZBP-89ΔN mRNA was co-expressed with its ZBP-89FL cognate in gastrointestinal cell lines and tissues. Similarly, ZBP-89ΔN protein was expressed. To define its function in vivo, we generated ZBP-89ΔN knock-in mice by targeting exon 4 that encodes the amino terminus. Homozygous ZBP-89ΔN mice, expressing only ZBP-89ΔN protein, experienced growth delay, reduced viability and increased susceptibility to dextran sodium sulfate colitis. We conclude that ZBP-89ΔN antagonizes ZBP-89FL function and that over-expression of the truncated isoform disrupts gastrointestinal homeostasis. PMID:16517939

  4. Chemistry meets biology in colitis-associated carcinogenesis

    PubMed Central

    Mangerich, Aswin; Dedon, Peter C.; Fox, James G.; Tannenbaum, Steven R.; Wogan, Gerald N.

    2015-01-01

    The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD) – a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation. PMID:23926919

  5. Acute ischemic colitis secondary to air embolism after diving.

    PubMed

    Payor, Austin Daniel; Tucci, Veronica

    2011-01-01

    Ischemic colitis (IC) secondary to air embolism from decompression sickness or barotrauma during diving is an extremely rare condition. After extensive review of the available literature, we found that there has been only one reported case of IC secondary to air embolism from diving. Although air embolization from diving and the various medical complications that follow have been well documented, the clinical manifestation of IC from an air embolism during diving is very rare and thus far unstudied. Common symptoms of IC include abdominal pain, bloody or non-bloody diarrhea or nausea or vomiting or any combination. Emergency physicians and Critical Care specialists should consider IC as a potential diagnosis for a patient with the above-mentioned symptoms and a history of recent diving. We report a case of IC from air embolism after a routine dive to 75 feet below sea level in a 53-year-old White female who presented to a community Emergency Department complaining of a 2-day history of diffuse abdominal pain and nausea. She was diagnosed by colonoscopy with biopsies and treated conservatively with antibiotics, bowel rest, and a slow advancement in diet.

  6. Foam preparations for the treatment of ulcerative colitis.

    PubMed

    Loew, Burr J; Siegel, Corey A

    2012-07-01

    Patients with ulcerative colitis uniformly have disease involving the distal colon. When patients have disease limited to the left colon or symptoms suggestive of active rectal inflammation, guidelines recommend topical rectal therapies as first-line agents either as monotherapy or in conjunction with oral products. Rectal delivery modalities offer the advantage of delivering high local concentrations of active medication to the site of maximal inflammation with minimization of systemic side effects. Methods of rectal administration include suppositories, liquid enemas and foams. Suppositories are limited to the treatment of rectal disease, and patients often have difficulty retaining the liquid enema secondary to its high volume and consistency. Rectal foams reliability extend to the descending and sigmoid colon with application. Foams are further characterized by increased viscosity, lower volumes, finer dispersion on the colonic mucosa, and increased adhesiveness to the colonic mucosa compared with liquid enemas. Additionally, rectal foam agents demonstrate equal efficacy to their liquid enema counterparts yet consistently yield better patient tolerance, lower incidence of side effects, and increased patient acceptability. Currently available agents include 5-aminosalicylic acid and corticosteroids, both first and newer generation. This review focuses on clinical trials assessing efficacy, tolerability, and patient preferences for these agents as well as describing the currently available rectal foam products.

  7. Proteins That Underlie Neoplastic Progression of Ulcerative Colitis

    PubMed Central

    Brentnall, Teresa A.; Pan, Sheng; Bronner, Mary P.; Crispin, David A.; Mirzaei, Hamid; Cooke, Kelly; Tamura, Yasuko; Nikolskaya, Tatiana; JeBailey, Lellean; Goodlett, David R.; McIntosh, Martin; Aebersold, Ruedi; Rabinovitch, Peter S.; Chen, Ru

    2009-01-01

    Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non-dysplastic mucosa; we hypothesized that the same field defect will include abnormally expressed proteins. Here we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared from 1) UC patients without dysplasia (non-progressors); 2) none-dysplastic colonic tissue from UC patient with high-grade dysplasia or cancer (progressors); 3) high-grade dysplastic tissue from UC progressors and 4) normal colon. We identified protein differential expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, calcium-binding proteins were some of interesting classes of these proteins. Network analysis discovered that Sp1 and c-myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over-expressed proteins in the non-dysplastic tissue of UC progressors, CPS1 and S100P, were further confirmed by IHC analysis. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non-dysplastic mucosa that identify a patient’s risk for UC dysplasia. PMID:20098637

  8. Herbal medicine in the treatment of ulcerative colitis.

    PubMed

    Ke, Fei; Yadav, Praveen Kumar; Ju, Liu Zhan

    2012-01-01

    Ulcerative colitis (UC) is a refractory, chronic, and nonspecific disease occurred usually in the rectum and the entire colon. The etiopathology is probably related to dysregulation of the mucosal immune response toward the resident bacterial flora together with genetic and environmental factors. Several types of medications are used to control the inflammation or reduce symptoms. Herbal medicine includes a wide range of practices and therapies outside the realms of conventional Western medicine. However, there are limited controlled evidences indicating the efficacy of traditional Chinese medicines, such as aloe vera gel, wheat grass juice, Boswellia serrata, and bovine colostrum enemas in the treatment of UC. Although herbal medicines are not devoid of risk, they could still be safer than synthetic drugs. The potential benefits of herbal medicine could lie in their high acceptance by patients, efficacy, relative safety, and relatively low cost. Patients worldwide seem to have adopted herbal medicine in a major way, and the efficacy of herbal medicine has been tested in hundreds of clinical trials in the management of UC. The evidences on herbal medicine are incomplete, complex, and confusing, and certainly associated with both risks and benefits. There is a need for further controlled clinical trials of the potential efficacy of herbal medicine approaches in the treatment of UC, together with enhanced legislation to maximize their quality and safety.

  9. Mucosal flora in Crohn's disease and ulcerative colitis - an overview.

    PubMed

    Swidsinski, A; Loening-Baucke, V; Herber, A

    2009-12-01

    The intestinal flora harbors varies pathogens. Clostridium perfringens (gas gangrene), Enterococci (endocarditis), Enterobacteriaceae (sepsis), Bacteroides (abscesses) are present in the large intestine of every healthy person in high concentrations. These bacteria are, however, separated from the colonic wall by an impenetrable mucus layer and are tolerated by the host. This separation is disturbed in patients with inflammatory bowel disease (IBD), where bacteria adhere to the mucosa and invade epithelial cells with concomitant inflammatory response. This chronic bowel inflammation can not subside as long as the mucus barrier remains defective. The inflammatory response interferes with the state of tolerance to the intestinal bacteria and leads to characteristic changes in the biostructure of the faecal microbiota. These changes in the biostructure of faecal microbiota are specific for active Crohn's disease and ulcerative colitis (UC) and can be longitudinally monitored. The reason for the defect of the mucus barrier in IBD patients is unclear. Epidemiologic studies indicate a negative role of western lifestyle and foods and document the rise in the incidence of IBD in the industrialized countries during the 20(th) century. In parallel to this, detergents were introduced in households and emulsifiers were increasingly added to food. The cleaning effect of these on the colonic mucus has to be investigated. The present contribution summarizes new data on the biostructure of the intestinal microbiota.

  10. Ulcerative colitis and Crohn's disease: factor XIII, inflammation and haemostasis.

    PubMed

    Seitz, R; Leugner, F; Katschinski, M; Immel, A; Kraus, M; Egbring, R; Göke, B

    1994-01-01

    An important role has been ascribed to plasma factor XIII (FXIII) in inflammation and wound healing. FXIII is necessary for fibrin stabilization and interacts with connective tissue and adhesive proteins and cells. In a prospective study, FXIII activity and parameters of coagulation, fibrinolysis and inflammation, were determined in patients with ulcerative colitis (UC; 13 active, 22 moderate) and Crohn's disease (CD; 36 active, 45 moderate). FXIII levels were lower in active than in moderate UC and CD, and were < 70% of normal values in 7/13 patients with active UC, and in 7/36 patients with active CD, although the median values did not fall below the normal range. FXIII was somewhat higher in active UC patients responding to therapy. The FXIII levels were widely scattered, and low values appear to be due to greatly enhanced turnover. A correlation between FXIII and the systemic levels of markers of activation of haemostasis and inflammation was lacking, but there was a correlation with the extent of bowel involvement. FXIII levels were lower in the patients with involvement beyond the sigmoid colon in CU (p = 0.0045), and both small and large bowel segments in CD (p = 0.0223) patients. This points to local consumption and/or loss of FXIII within the inflamed tissue, and provides an argument for FXIII substitution in the treatment of acute episodes of inflammatory bowel diseases.

  11. Optimal management of steroid-dependent ulcerative colitis

    PubMed Central

    Khan, Hafiz M Waqas; Mehmood, Faisal; Khan, Nabeel

    2015-01-01

    Ulcerative colitis (UC) is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs) were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date. PMID:26648749

  12. Serum bactericidal resistance of faecal Escherichia coli and bactericidal competence of serum from patients with ulcerative colitis.

    PubMed

    Burke, D A; Clayden, S A; Axon, A T

    1990-04-01

    A microtitre method was developed to screen Escherichia coli from 48 patients with ulcerative colitis and 25 controls for serum resistance. Bactericidal resistance was indicated by a change in colour of indicator due to acid production by viable organisms and quantitated by a change in absorbance. The method clearly differentiated between organisms confirmed as resistant or sensitive by conventional techniques. Twenty four (50%) disease and 14 (56%) control E coli specimens showed serum resistance. Bactericidal competence of sera from patients with ulcerative colitis was assessed by incubating sensitive E coli with sera from 10 patients with ulcerative colitis and pooled normal serum. All sera effectively reduced viable counts to less than 6% of original inoculum. This study shows that serum samples from patients with ulcerative colitis are bactericidally competent and that there is no increase in the number of serum resistant E coli in patients with ulcerative colitis.

  13. Salmonella colitis: assessment with double-contrast barium enema examination in seven patients.

    PubMed

    Nakamura, S; Iida, M; Tominaga, M; Yao, T; Hirata, N; Fujishima, M

    1992-08-01

    To completely rule out the possibility of ulcerative colitis, Crohn disease, and other diseases, the authors analyzed the radiographic findings at double-contrast barium enema examination performed in seven patients with colitis caused by Salmonella organisms. In all patients, bacteriologic confirmation of nontyphoid Salmonella infection and radiographs of the upper gastrointestinal tract were obtained. Total colonoscopy was performed in five patients and sigmoidoscopy in one patient. In all patients, the radiographic findings were retrospectively analyzed. The descending colon and sigmoid colon were affected in six patients, whereas the rectum was affected in none. The findings included fine mucosal granularity (seven patients), loss of haustration (six patients), many fine ulcerations (five patients), and multiple ulcers (two patients). The radiographic features simulated those of ulcerative colitis, except for absence of rectal abnormality. It is concluded that double-contrast barium enema examination is useful for detection of fine mucosal changes. PMID:1620861

  14. A diet with lactosucrose supplementation ameliorates trinitrobenzene sulfonic acid-induced colitis in rats.

    PubMed

    Zhou, Yan; Ruan, Zheng; Zhou, Xiaoli; Huang, Xiaoliu; Li, Hua; Wang, Ling; Zhang, Cui; Liu, Shiqiang; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2015-01-01

    Chronic intestinal inflammation contributes to an increased risk of colon cancer. Lactosucrose (LS), a kind of functional trisaccharide, can modulate immunity and promote microbe growth. The aim of this study was to investigate the effect of LS on 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colitis in rats. Rats were randomly divided into four treatment groups: the normal group, TNBS group, LS group, and salicylazosulfapyridine (SASP) group for five weeks. LS supplementation ameliorated TNBS-induced colitis. LS supplementation increased IL-10 production and suppressed the secretion of IL-12 in the colon, as compared to the TNBS group. LS decreased the production of TLR-2 protein and nuclear NF-κB p65 protein, as well as mRNA levels, as compared with colitic rats. These results indicate that chronic feeding of LS inhibited TNBS-induced chronic inflammation. LS has potential nutraceutical intervention to combat colitis.

  15. MDCT of acute colitis in adults: an update in current imaging features.

    PubMed

    Barral, M; Boudiaf, M; Dohan, A; Hoeffel, C; Camus, M; Pautrat, K; Fishman, E K; Cohen, S; Soyer, P

    2015-02-01

    Acute colitis is often diagnosed on multidetector row computed tomography (MDCT) because patients with this condition present with abdominal pain and a variety of nonspecific symptoms. Acute colitis has multiple causes with varying degrees of severity. Analysis of the extent of colonic involvement, presence of specific MDCT imaging features and associated signs should help radiologist narrow the diagnosis. Integrating the results of clinical examination and biological tests is mandatory, and in case of ambiguous or nonspecific MDCT findings, endoscopy and colon biopsy should always be considered for a definite diagnosis. The purpose of this review is to discuss and illustrate MDCT features that are helpful for characterizing acute colitis in adults and to provide an update in current MDCT features. PMID:24835625

  16. MDCT of acute colitis in adults: an update in current imaging features.

    PubMed

    Barral, M; Boudiaf, M; Dohan, A; Hoeffel, C; Camus, M; Pautrat, K; Fishman, E K; Cohen, S; Soyer, P

    2015-02-01

    Acute colitis is often diagnosed on multidetector row computed tomography (MDCT) because patients with this condition present with abdominal pain and a variety of nonspecific symptoms. Acute colitis has multiple causes with varying degrees of severity. Analysis of the extent of colonic involvement, presence of specific MDCT imaging features and associated signs should help radiologist narrow the diagnosis. Integrating the results of clinical examination and biological tests is mandatory, and in case of ambiguous or nonspecific MDCT findings, endoscopy and colon biopsy should always be considered for a definite diagnosis. The purpose of this review is to discuss and illustrate MDCT features that are helpful for characterizing acute colitis in adults and to provide an update in current MDCT features.

  17. A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use

    PubMed Central

    Govil, Yogesh

    2016-01-01

    A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative for C. difficile. CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use.

  18. [Search of a cytomegalovirus infection during pseudo-membranous colitis. 6 cases (author's transl)].

    PubMed

    Beaugrand, M; Poynard, T; Callard, P; Ferrier, J P; Bernades, P; Molas, G; Ferchal, F; Perol, Y

    1981-04-01

    Six patients with pseudomembranous colitis unrelated to lincomycin or clindamycin treatment were investigated for signs of localised or diffuse cytomegalovirus (CMV) infection. Before the onset of colitis 3 patients had receive prednisone, associated in 2 of them with immunosuppressive drugs. Testing for CMV included rectal mucosa biopsies, culture of blood leucocytes with human embryo diploid fibroblasts in continuous layer and titration of complement-deviating anti-CMV antibodies. Cytomegalic cells with nuclear inclusion bodies were found in the rectal mucosa of 5 patients, 4 of whom also had foci of CMV-infected cells in leucocyte-fibroblast cultures, indicative of viraemia. The fifth patient was not tested for viraemia but developed very high anti-CMV antibodies titers at a later stage. These results show that pseudomembranous colitis that are not due to antibiotics are frequently associated with localised or diffuse CMV infection. Viral invasion of the colon might be encouraged by a state of immunodeficiency.

  19. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis.

  20. Boehmeria nivea Attenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

    PubMed Central

    Shin, Eun Ju; Sung, Mi Jeong; Yang, Hye Jeong; Kim, Myung Sunny; Hwang, Jin-Taek

    2014-01-01

    We examined the therapeutic effect of an ethanol extract derived from Boehmeria nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500 mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that B. nivea extract is effective in preventing colitis. PMID:25045208

  1. A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use.

    PubMed

    Goyal, Abhinav; Salahuddin, Moiz; Govil, Yogesh

    2016-01-01

    A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative for C. difficile. CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use. PMID:27668102

  2. Deficient interleukin 2 dependent proliferation pathway in T lymphocytes from active and inactive ulcerative colitis patients.

    PubMed Central

    Manzano, L; Alvarez-Mon, M; Vargas, J A; Girón, J A; Abreu, L; Fernández-Corugedo, A; Román, L I; Albarran, F; Durántez, A

    1994-01-01

    There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients. PMID:8063224

  3. Role and species–specific expression of colon T cell homing receptor GPR15 in colitis

    PubMed Central

    Nguyen, Linh P.; Pan, Junliang; Dinh, Theresa Thanh; Hadeiba, Husein; O’Hara, Edward; Ebtikar, Ahmad; Hertweck, Arnulf; Gökmen, M. Refik; Lord, Graham M.; Jenner, Richard G.

    2014-01-01

    Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells, and is required for colitis in a model that depends on their trafficking to the colon. In humans GPR15 is expressed by effector cells including pathogenic TH2 cells in ulcerative colitis, but is not expressed by regulatory T (Treg) cells. The TH2 transcriptional activator GATA-3 and the Treg–associated transcriptional repressor FOXP3 robustly bind human, but not mouse, GPR15 enhancer sequences, correlating with expression. Our results highlight species differences in GPR15 regulation, and suggest it as a potential therapeutic target for colitis. PMID:25531831

  4. Neutrophils Are a Source of Gamma Interferon during Acute Salmonella enterica Serovar Typhimurium Colitis

    PubMed Central

    Spees, Alanna M.; Kingsbury, Dawn D.; Wangdi, Tamding; Xavier, Mariana N.; Tsolis, Renée M.

    2014-01-01

    Gamma interferon (IFN-γ) is an important driver of intestinal inflammation during colitis caused by Salmonella enterica serovar Typhimurium. Here we used the mouse colitis model to investigate the cellular sources of IFN-γ in the cecal mucosa during the acute phase of an S. Typhimurium infection. While IFN-γ staining was detected in T cells, NK cells, and inflammatory monocytes at 2 days after infection, the majority of IFN-γ-positive cells in the cecal mucosa were neutrophils. Furthermore, neutrophil depletion blunted mucosal Ifng expression and reduced the severity of intestinal lesions during S. Typhimurium infection. We conclude that neutrophils are a prominent cellular source of IFN-γ during the innate phase of S. Typhimurium-induced colitis. PMID:24421037

  5. 'Sticky' neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.

    PubMed Central

    Dwarakanath, A D; Yu, L G; Brookes, C; Pryce, D; Rhodes, J M

    1995-01-01

    Pyoderma gangrenosum is strongly associated with inflammatory bowel disease and exhibits pathergy, occurring at sites of previous minor trauma. A patient is presented with a 21 year history of extensive ulcerative colitis, who developed pyoderma gangrenosum and arthralgia while receiving high dose corticosteroids for active ulcerative colitis. The arthralgia exhibited pathergy affecting particularly the left temporomandibular joint, which was stressed by an asymmetric bite, and the left elbow, which had been fractured many years previously. This prompted the hypothesis that neutrophils in this condition may be marginated, as a result of increased stickiness of either the neutrophil or the vascular endothelium. The introduction of heparin therapy was associated with rapid resolution of the arthralgia, pyoderma gangrenosum, and ulcerative colitis. Images Figure 1 Figure 3 PMID:7489951

  6. A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use

    PubMed Central

    Govil, Yogesh

    2016-01-01

    A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative for C. difficile. CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use. PMID:27668102

  7. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice

    PubMed Central

    Dziarski, Roman; Dowd, Scot E.; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species. PMID

  8. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.

    PubMed

    Dziarski, Roman; Park, Shin Yong; Kashyap, Des Raj; Dowd, Scot E; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.

  9. Ulcerative colitis--a disease characterised by the abnormal colonic epithelial cell?

    PubMed

    Gibson, P R; van de Pol, E; Barratt, P J; Doe, W F

    1988-04-01

    The leakiness of the cell membranes of colonic epithelial cells isolated by the collagenase/Dispase technique from normal or diseased colons was assessed in a 4 h 51Cr release assay. Cells from normal, adenoma bearing or cancer bearing colons showed 51Cr release of 8% or less in almost all of 46 cell populations tested. In contrast, cells from mucosa affected by ulcerative colitis [11.9 (4.3%) n = 23] or Crohn's disease [8.4 (2.7%) n = 18] released significantly more 51Cr than the non-inflamed groups. Values are expressed as mean (SD). Overall, release values were greater in ulcerative colitis than Crohn's disease (p less than 0.01). In Crohn's disease, cells obtained from histologically inflamed mucosa released significantly more 51Cr [9.7 (2.5%) n = 11] than those from non-inflamed mucosa [6.4 (1.5%) n = 7, p less than 0.02] whereas, in ulcerative colitis, abnormal release values were found in 8 of 13 cell populations isolated from mucosa showing no histological evidence of active disease. In five patients with distal ulcerative colitis, cells from mucosa not apparently involved demonstrated normal 51Cr release in four of five studies despite abnormal release from cells from involved mucosa suggesting that a diffuse abnormality of the colonic epithelial cell is not usually present. These data indicate that chronic mucosal inflammation per se is associated with abnormalities of the colonic epithelial cell but that, in ulcerative colitis, the abnormality remains in many patients with quiescent disease. Identification of the local factors responsible for such an abnormality may contribute to an understanding of the pathogenesis of ulcerative colitis. PMID:3371720

  10. Effects of bacteria‑mediated reprogramming and antibiotic pretreatment on the course of colitis in mice.

    PubMed

    Gardlik, Roman; Wagnerova, Alexandra; Celec, Peter

    2014-08-01

    Since the original study by Takahashi and Yamanaka in 2006, there have been significant advances in the field of induced pluripotent stem cells. However, to the best of our knowledge, all of the studies published to date are based on ex vivo gene delivery and subsequent reimplantation of the cells. By contrast, in vivo reprogramming allows the direct administration of DNA encoding the reprogramming factors into the target tissue. In our previous study we demonstrated the beneficial effects of Salmonella‑mediated oral delivery of genes into colonic mucosa as a therapy for colitis. In the present study, the effect of the bacterial vector Salmonella typhimurium SL7207, carrying a plasmid encoding the reprogramming factors Sox2, Oct3/4 and Klf4, on colitis in mice was investigated. Therapeutic intervention, consisting of repeated gavaging following the induction of colitis, did not exhibit beneficial effects. However, preventive oral administration of the therapeutic bacterial strain resulted in improvements in weight loss, colon length and stool consistency. Recently it has been shown that antibiotic pretreatment may alleviate chemically induced colitis in mice. Therefore, in the present study it was investigated whether antibiotic pretreatment of mice was able to enhance colonization of the administered bacterial strain in the colon, and therefore improve therapeutic outcome. C57BL/6 mice were administered streptomycin and metronidazole for four days, prior to multiple oral administrations of therapeutic bacteria every other day. Following three gavages, mice were administered dextran sulfate sodium in their drinking water to induce colitis. Disease activity parameters, including stool consistency, weight loss and colon length, were improved in the group receiving antibiotics and bacterial vectors. These results indicate that antibiotic pretreatment may enhance bacterial gene delivery into the colon. Furthermore, the anticipated in vivo reprogramming of colon

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

    PubMed

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

    2015-07-01

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

  12. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

    PubMed

    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-01

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression.

  13. Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis

    PubMed Central

    Papatheodoridis, G; Hamilton, M; Mistry, P; Davidson, B; Rolles, K; Burroughs, A

    1998-01-01

    Background—The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity. 
Aims—To evaluate the course of inflammatory bowel disease in primary sclerosing cholangitis transplant patients who were treated without long term steroids. 
Methods—Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived more than 12 months. Ulcerative colitis was diagnosed in 18 (60%) patients before transplantation; two had previous colectomy. All patients underwent colonoscopy before and after transplantation and were followed for 38 (12-92) months. All received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression. 
Results—Ulcerative colitis course after transplantation compared with that up to five years before transplantation was the same in eight (50%) and worse in eight (50%) patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened in all four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients without inflammatory bowel disease before transplantation. No colorectal cancer has been diagnosed to date. 
Conclusions—Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis and treated without long term steroids. 

 Keywords: liver transplantation; inflammatory bowel disease; ulcerative colitis; primary sclerosing cholangitis; immunosuppression PMID:9824344

  14. Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats

    PubMed Central

    Chung, Ho-Lam; Yue, Grace Gar-Lee; To, Ka-Fai; Su, Ya-Lun; Huang, Yu; Ko, Wing-Hung

    2007-01-01

    AIM: To investigate the effect of Scutellariae Radix extract (SRE) on ulcerative colitis (UC) in rats induced by dextran-sulfate sodium (DSS). METHODS: Colitis was induced in male Sprague-Dawley (SD) rats (170-180 g) by 4% dextran sulfate sodium (DSS, wt/v; MW 54000) in drinking water for 8 d. The treated rats received 4% DSS and SRE orally (100 mg/kg per day). Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase (MPO) activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique. RESULTS: Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening and ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the ISC responses of the colonic mucosa to forskolin were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness. CONCLUSION: SRE was effective in treating acute DSS-induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function. PMID:17948935

  15. Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark

    PubMed Central

    Pedersen, Bo V; Andersson, Roland E

    2009-01-01

    Objective To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis. Design Nationwide cohort studies. Setting Sweden and Denmark. Participants 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease. Main outcome measures Standardised incidence ratios and rate ratios as measures of relative risk. Results During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed v 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, v no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74). Conclusions In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis. PMID:19273506

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

    PubMed Central

    2016-01-01

    Introduction Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. Material and methods The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Results Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. Conclusions The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem. PMID:27186172

  17. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice

    PubMed Central

    Hassan, Ahmed M.; Jain, Piyush; Reichmann, Florian; Mayerhofer, Raphaela; Farzi, Aitak; Schuligoi, Rufina; Holzer, Peter

    2014-01-01

    Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis. PMID:25414650

  18. [Haemorrhagic colitis in a young male after the use of amoxicillin].

    PubMed

    van Hensbroek, P Boele; Hack, W W M; Labadie, J

    2005-12-31

    A 16-year-old boy had rectal blood loss due to haemorrhagic colitis probably resulting from oral and intravenous administration of amoxicillin. He also had haemolytic anaemia and thrombocytopenia, both also most likely resulting from the use of amoxicillin and/or ibuprofen. In the week following the discontinuation of amoxicillin and ibuprofen, the symptoms of bloody diarrhoea disappeared spontaneously and the blood picture became normal. Haemorrhagic colitis is a known side effect of amoxicillin that is rarely seen. Discontinuation of treatment typically results in a quick and uneventful recovery.

  19. Diphtheroid colitis in a Boa constrictor infected with amphibian Entamoeba sp.

    PubMed

    Richter, Barbara; Kübber-Heiss, Anna; Weissenböck, Herbert

    2008-05-01

    A female boa (Boa constrictor) from a zoological collection was submitted for necropsy after sudden death. Prominent pathological findings included a diphtheroid colitis, endoparasitism, focal pneumonia and inclusion bodies typical for inclusion body disease (IBD). In the colon entamoebae were identified, which differed in size and distribution from Entamoeba invadens. Gene sequence analysis of the 18S ribosomal RNA revealed 100% similarity with an Entamoeba species from the African bullfrog (Pyxicephalus adspersus), probably Entamoeba ranarum. The snake was possibly immunosuppressed, and the source of infection remains unclear. This is the first report of an infection with an amphibian Entamoeba species associated with colitis in a snake.

  20. Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis

    PubMed Central

    Tang, Yueming; Preuss, Fabian; Turek, Fred W.; Jakate, Shriram; Keshavarzian, Ali

    2012-01-01

    Background and aim We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage. Methods Acute sleep deprivation (ASD) consisted of 24 h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6 h every other day throughout the 10 day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7 days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10 days after initiation of colitis. Results ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from

  1. An Autopsy Case of Fulminant Amebic Colitis in a Patient with a History of Rheumatoid Arthritis.

    PubMed

    Kawabe, Naoko; Sato, Fuyuki; Nagasawa, Miho; Nakanishi, Masako; Muragaki, Yasuteru

    2016-01-01

    Generally, amebic colitis is localized around the mucosal membrane and often accompanied by diarrhea and abdominal pain. We describe a patient with a history of rheumatoid arthritis who had received prolonged steroid therapy. The patient complained of breathing difficulties because of rheumatoid lung disease. Although the patient was given antibacterial agent, the symptoms did not improve until death. We did an autopsy and found that he had fulminant amebic colitis, although the patient was not previously examined. Histochemical analysis revealed severe inflammation and full-thickness necrosis of the colon by ameba, suggesting the involvement of ameba in the progression of the overall condition. PMID:27382497

  2. An Autopsy Case of Fulminant Amebic Colitis in a Patient with a History of Rheumatoid Arthritis

    PubMed Central

    Kawabe, Naoko; Nagasawa, Miho; Nakanishi, Masako

    2016-01-01

    Generally, amebic colitis is localized around the mucosal membrane and often accompanied by diarrhea and abdominal pain. We describe a patient with a history of rheumatoid arthritis who had received prolonged steroid therapy. The patient complained of breathing difficulties because of rheumatoid lung disease. Although the patient was given antibacterial agent, the symptoms did not improve until death. We did an autopsy and found that he had fulminant amebic colitis, although the patient was not previously examined. Histochemical analysis revealed severe inflammation and full-thickness necrosis of the colon by ameba, suggesting the involvement of ameba in the progression of the overall condition. PMID:27382497

  3. Dextran Sulfate Sodium (DSS)-Induced Acute Colitis in the Rat.

    PubMed

    Martin, Jérôme C; Bériou, Gaëlle; Josien, Régis

    2016-01-01

    Inflammatory bowel diseases (IBDs) are complex multifactorial disease thought to result from inappropriate immune responses to the gut microbiota, in genetically susceptible individuals, under the influence of environmental factors. Among the different animal models developed to help in understanding IBDs pathophysiological mechanisms as well as to achieve pharmacological preclinical studies, the dextran sulfate sodium (DSS)-induced colitis model is the most widely used because of its simplicity, cost-effectiveness, and similarity with human IBDs. This section provides with a detailed protocol that we validated in our laboratory to perform DSS-induced acute colitis in the Sprague-Dawley (SPD) rat.

  4. Oral tolerance is inducible during active dextran sulfate sodium-induced colitis

    PubMed Central

    Ino, Satoshi; Kohda, Chikara; Takeshima, Kosuke; Ishikawa, Hiroki; Norose, Tomoko; Yamochi, Toshiko; Takimoto, Masafumi; Takahashi, Hiroshi; Tanaka, Kazuo

    2016-01-01

    AIM: To investigate whether oral tolerance is inducible during the active phase of dextran sulfate sodium (DSS)-induced colitis. METHODS: Colitis was induced in 6- to 8-wk-old female BALB/c mice by the administration of 2% DSS. To induce oral tolerance, mice that received water with DSS [DSS (+)] and mice that received autoclaved water [DSS (-)] were intragastrically (i.g.) administered ovalbumin (OVA) as a tolerogen before systemic challenge with OVA. Following this, serum levels of OVA-specific IgE antibodies were measured. In mice with active colitis, CD4+CD25+Foxp3+ cell and B10 cell frequencies were evaluated using flow cytometry. Cytokine mRNA expression profiles were evaluated by reverse transcription real-time polymerase chain reaction. RESULTS: Regardless of the presence of DSS colitis, OVA-specific immunoglobulin E concentrations were significantly reduced in mice that were i.g. administered OVA compared to mice that were i.g. administered PBS [DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01; DSS (-): 27.7 (0.1-54.5) ng/mL vs 116.5 (80.6-213.6) ng/mL, P < 0.01]. These results demonstrated that oral tolerance was induced in both the presence and absence of colitis. In the spleen and mesenteric lymph nodes (MLN), the frequencies of CD4+CD25+Foxp3+ cells and B10 cells, both of which are associated with oral tolerance, did not significantly change. In the spleen, interferon-γ mRNA expression significantly decreased in mice with colitis [DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]. The expression levels of other cytokines did not significantly change. CONCLUSION: Oral tolerance is inducible during active DSS colitis. The stability of regulatory cell populations in the spleen and MLN in colitis might correlate with these results. PMID:27158540

  5. Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs.

    PubMed

    Hostutler, Roger A; Luria, Brian J; Johnson, Susan E; Weisbrode, Steven E; Sherding, Robert G; Jaeger, Jordan Q; Guilford, W Grant

    2004-01-01

    Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid-Schiff (PAS)-positive macrophages. The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture. Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia. Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole. Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin). Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated. Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3-12 days. Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2-7 days. Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement. The increase in body weight after treatment was statistically significant (P = .01). Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months. These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment.

  6. Recombinant probiotic therapy in experimental colitis in mice.

    PubMed

    Gardlik, R; Palffy, R; Celec, P

    2012-01-01

    Recently, high interest has been attracted to the research of inflammatory bowel diseases (IBD). Recombinant probiotic bacteria may represent an interesting way to influence the course of IBD. Their benefits include cheap and simple production and easy manipulation of the genetic material. Several gene therapy and probiotic approaches already showed promising results in the past. The aim of this study was to test the probiotic potential of IL-10-expressing Escherichia coli Nissle 1917 in a mouse model of IBD and to compare it with control bacterial strains. The dextran sulphate sodium (DSS) model of colitis was examined for this purpose. Animals received control probiotic bacteria or modified probiotics (expressing IL-10) via gastric gavage. Body weight, stool consistency, food and water consumption were monitored. At the end of the experiment, the parameters of inflammation, oxidative stress and carbonyl stress were analysed in the samples and statistical analysis was performed. We prepared an anti-inflammatory probiotic Escherichia coli strain that we designated Nissle 1917/pMEC-IL10 and proved its anti-inflammatory properties, which are similar to those of the control probiotic strains Nissle 1917 and Lactococcus lactis/pMEC-IL10 in vivo. The probiotic therapy was successful according to several parameters, including colon length, and oxidative and carbonyl stress. Bacterially produced IL-10 was detected in the plasma. The potential of bacterial anti-inflammatory therapy of IBD using modified probiotics was outlined. The results opened a way for upcoming studies using modified probiotics for therapy of systemic diseases. PMID:23438849

  7. Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis

    PubMed Central

    Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

    2016-01-01

    Abstract Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC. A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome. Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6–39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I2 = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events. FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT. PMID:27281075

  8. Sympathetic overactivity in active ulcerative colitis: effects of clonidine.

    PubMed

    Furlan, Raffaello; Ardizzone, Sandro; Palazzolo, Laura; Rimoldi, Alexandra; Perego, Francesca; Barbic, Franca; Bevilacqua, Maurizio; Vago, Luca; Bianchi Porro, Gabriele; Malliani, Alberto

    2006-01-01

    Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.

  9. Spironolactone and colitis: Increased mortality in rodents and in humans

    PubMed Central

    Johnson, Laura A.; Govani, Shail M.; Joyce, Joel C.; Waljee, Akbar K.; Gillespie, Brenda W.; Higgins, Peter D. R.

    2011-01-01

    Background and Methods Crohn’s disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an anti-fibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is anti-fibrotic in the context of intestinal inflammation. In vitro, spironolactone repressed fibrogenesis in TGFβ-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since IBD patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n=390 deaths, p<0.0001). In patients without liver disease, the adjusted OR for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% CI: 1.51 – 2.63) In contrast to the main effect of spironolactone mortality, multivariable modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted odds ratio for mortality after CDI was 1.96 (95% CI: 1.50 – 2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82 – 2.00) for patients with liver disease on spironolactone, when compared to a reference group without liver disease or spironolactone use. Conclusions We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the US. PMID:22081497

  10. Corticosteroid therapy in ulcerative colitis: Clinical response and predictors

    PubMed Central

    Li, Jin; Wang, Fan; Zhang, Hong-Jie; Sheng, Jian-Qiu; Yan, Wen-Feng; Ma, Min-Xing; Fan, Ru-Ying; Gu, Fang; Li, Chuan-Feng; Chen, Da-Fan; Zheng, Ping; Gu, Yu-Pei; Cao, Qian; Yang, Hong; Qian, Jia-Ming; Hu, Pin-Jin; Xia, Bing

    2015-01-01

    AIM: To evaluate clinical response to initial corticosteroid (CS) treatment in Chinese ulcerative colitis patients (UC) and identify predictors of clinical response. METHODS: Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China, and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors. Short-term outcomes within one month were classified as primary response and primary non-response. Long-term outcomes within one year were classified as prolonged CS response, CS dependence and secondary non-response. CS refractoriness included primary and secondary non-response. Multivariate analyses were performed to identify predictors associated with clinical response. RESULTS: Within one month, 95.0% and 5.0% of the cases were classified into primary response and non-response, respectively. Within one year, 41.6% of cases were assessed as prolonged CS response, while 49.5% as CS dependence and 4.0% as secondary non-response. The rate of CS refractoriness was 8.9%, while the cumulative rate of surgery was 6.9% within one year. After multivariate analysis of all the variables, tenesmus was found to be a negative predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P = 0.040). After one-month treatment, sustained high Sutherland score (≥ 6) also predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION: Tenesmus was a negative predictor of CS dependence, while weight loss and sustained high Sutherland score were strongly associated with poor CS response. PMID:25780299

  11. Surgical Principles in the Treatment of Ulcerative Colitis

    PubMed Central

    Kühn, Florian; Klar, Ernst

    2015-01-01

    Summary Background The primary treatment of ulcerative colitis (UC) is conservative; surgical intervention is carried out in the case of therapy-refractory situation, imminent or malignant transformation, or complications. Surgery for UC should be indicated by interdisciplinary means. Despite the development of drug therapy – in particular the introduction of biologics -, a surgical intervention becomes necessary in a relevant proportion of patients with UC throughout lifetime. Methods A selective literature search was conducted, taking into account the current studies, reviews, meta-analyses, and guidelines. PubMed served as a database. The present work gives an overview of the surgical options, outcome as well as peri- and postoperative management for patients with UC. Results Approximately 20% of patients with UC will require surgery during the course of their disease. The rate of colectomy after a disease duration of 10 years is at approximately 16%. Unlike Crohn's disease, UC is principally surgically curable since it is naturally limited to the colon and rectum. Restorative proctocolectomy with an ileal pouch-anal anastomosis represents the surgical treatment of choice. Large studies show a postoperative complication rate of around 30% and a low mortality of 0.1% for this procedure. Chronic pouchitis is one of the main factors limiting the surgical success of curing UC. Despite a high postoperative complication rate, there is a long-term pouch success rate of >90% after 10 and 20 years of follow-up. Conclusion A close cooperation between the various disciplines in the pre- and postoperative setting is essential for an optimal outcome of patients with UC. Despite a 30% rate of early postoperative complications, normal quality of life can ultimately be reached in more than 90% of patients in experienced centers. PMID:26557832

  12. Nutritional modulators of ulcerative colitis: clinical efficacies and mechanistic view.

    PubMed

    Sung, Mi-Kyung; Park, Mi-Young

    2013-02-21

    Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses. PMID:23467687

  13. RORγt(+) hematopoietic cells are necessary for tumor cell proliferation during colitis-associated tumorigenesis in mice.

    PubMed

    Martin, Maria; Kesselring, Rebecca K; Saidou, Balam; Brunner, Stefan M; Schiechl, Gabriela; Mouris, Verena F; Wege, Anja K; Rümmele, Petra; Schlitt, Hans J; Geissler, Edward K; Fichtner-Feigl, Stefan

    2015-06-01

    Colorectal cancer (CRC) is one of the most common tumor entities. In patients with inflammatory bowel diseases, the development of colitis-associated colon cancer is considered a dangerous long-term complication. IL-17A and the transcription factor retinoic acid receptor-related orphan receptor γt (RORγt) play fundamental roles in the pathogenesis of inflammatory bowel diseases; in human studies, we detected a dense infiltration of RORγt-dependent CD4(+) IL17A(+) T helper (Th)17 cells in specimens of CRC, ulcerative colitis, and ulcerative colitis-associated colorectal cancer. However, the mechanistic role of RORγt(+) hematopoietic cells in colitis-associated tumorigenesis remains unclear. To investigate colitis-associated colon tumorigenesis, we conducted studies in the AOM+DSS mouse model that revealed the importance of RORγt for colon tumor progression. In the absence of RORγt-dependent Th17 lymphocytes, mice showed signs of intense chronic colitis, but developed significantly fewer macroscopic tumor nodules. The reduction of tumor development in RORγt(-/-) mice was not due to reduced colon tumor initiation. However, the proliferation rate of tumor cells was reduced in the absence of RORγt-dependent Th17 cells and tumor cells showed pronounced signs of senescence-associated epigenetic and lysosomal changes. These results indicate an important role for the immunological milieu in colitis-associated cancer, which is shaped in-part by RORγt-dependent Th17 lymphocytes that support CRC growth.

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

    SciTech Connect

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

    2009-05-15

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

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

    PubMed

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

    2015-05-27

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

  16. Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

    PubMed Central

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

    2016-01-01

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

  17. Protective effect of royal jelly in 2,4,6 trinitrobenzene sulfonic acid-induced colitis in rats

    PubMed Central

    Karaca, Turan; Uz, Yesim Hulya; Demirtas, Selim; Karaboga, Ihsan; Can, Guray

    2015-01-01

    Objective(s): In the present study, we evaluated immunological and immunomodulatory properties of royal jelly (RJ) in 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and Methods: Eighteen adult female Wistar albino rats were divided into three groups of six animals each: a control group that received only saline solution, a TNBS-induced colitis group, and a TNBS-colitis+RJ group that received 250 mg/kg/day of RJ for seven days before the induction of colitis, following by the same treatment for an additional seven days. At the end of the experiment, cardiac blood and colon samples were obtained under deep anaesthesia from the animals in all groups. Serum interleukin-1β (IL-1β), tumour necrosis factor-alpha (TNF-α) and IL-10 levels were analyzed with an enzyme-linked immunosorbent assay (ELISA). Five-micrometre-thick sections were stained with haematoxylin-eosin (H&E) for microscopic evaluations. For immunohistochemical evaluations, the paraffin sections were stained with anti-CD3 (cluster of differentiation), anti-CD5, anti-CD8 and anti-CD45. Results: The results showed that the oral RJ treatment inhibited proinflammatory cytokines, IL-1β and TNF-α secretion, while increasing anti-inflammatory cytokine IL-10 production in the TNBS-induced colitis+RJ group compared with the colitis group not treated with RJ. The colitis was not as severe in the colitis+RJ group, with ulcerative damage, weight loss and inflammatory scores suggesting that impaired CD3-, CD5-, CD8- and CD45-positive T cell immune responses likely mediated the anti-inflammatory effect. Conclusion: The antioxidant and anti-inflammatory properties of RJ protected colon mucosa against TNBS-induced colitis in rats orally treated with RJ. PMID:26019800

  18. The role of endoscopic assessment in ulcerative colitis in the era of infliximab.

    PubMed

    Daperno, M; Sostegni, R; Pera, A; Rognone, D; Rigazio, C; Ercole, E; Crocellà, L; Lavagna, A; Rocca, R

    2008-07-01

    Endoscopic evaluation of mucosal appearance is important for the clinical management of ulcerative colitis patients, as it offers valuable prognostic tools and data useful to change the management and treatment strategies. In the field of severe ulcerative colitis, partial endoscopy and bioptic sampling allows to obtain additional and relevant prognostic information: if severe endoscopic lesions are present, response to standard treatment is less likely, and if CMV superinfection is detected, anti-viral treatment should be added to conventional treatments. When clinical remission is obtained with conventional treatments, distal colonoscopy may add valuable data: the occurrence of complete endoscopic healing is a major predictor of long-term remission with no clinical activity. Finally, biologic treatments, and mainly infliximab, were shown to induce remarkable and significant mucosal healing also in ulcerative colitis, and patients with complete endoscopic healing in response to infliximab were shown to be more likely to experience fewer clinical relapses during the follow-up. Therefore endoscopic evaluation has to be considered a major prognostic marker in ulcerative colitis. In this review data from the Literature supporting this role will be reviewed. PMID:18598992

  19. Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

    PubMed Central

    Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi

    2014-01-01

    Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC. PMID:25120575

  20. Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

    PubMed Central

    Xiong, Jing; Zhou, Ming-feng; Wang, Ya-dong; Chen, Li-ping; Xu, Wan-fu; Wang, Yao-dong; Deng, Fan; Liu, Si-de

    2016-01-01

    Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2WT/WT) and PKD2 catalytic activity deficient mice (PKD2SSAA/SSAA) with dextran sulfate sodium. PKD2SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function. PMID:27659202

  1. Ischemic colitis induced by the newly reformulated multicomponent weight-loss supplement Hydroxycut®

    PubMed Central

    Sherid, Muhammed; Samo, Salih; Sulaiman, Samian; Gaziano, Joseph H

    2013-01-01

    Ischemic colitis accounts for 6%-18% of causes of acute lower gastrointestinal bleeding. It is more often multifactorial and more common in elderly. Drugs are considered important causative agents of this disease with different mechanisms. In this paper, we describe a 37-year-old otherwise healthy female presented with sudden onset diffuse abdominal pain and bloody stool. Radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her only suspected factor was hydroxycut which she had been taking for a period of 1 mo prior to her presentation. Her condition improved uneventfully after cessation of hydroxycut, bowel rest, intravenous hydration, and antibiotics. This is a first case of ischemic colitis with clear relationship with hydroxycut use (Naranjo score of 7). Our case demonstrates the importance of questioning patients regarding the usage of dietary supplements; especially since many patients consider them safe and do not disclose their use voluntarily to their physicians. Hydroxycut has to be considered as a potential trigger for otherwise unexplained ischemic colitis. PMID:23596542

  2. Induction of colitis in mice with food allergen-specific immune response

    PubMed Central

    Li, Lin-Jing; Zeng, Lu; Li, Xiao-Xi; Mo, Li-Hua; Geng, Xiao-Rui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Feng, Bai-Sui; Yang, Ping-Chang

    2016-01-01

    The pathogenesis of intestinal chronic inflammation is unclear. Food allergy plays an important role in the induction of intestinal inflammation. This study aims to test a hypothesis that food allergy initiates colitis. In this study, BALB/c mice were sensitized to a common food allergen, ovalbumin (OVA) with cholera toxin (CT) as an adjuvant. The colon epithelial barrier function was assessed with Ussing chamber technique. Expression of T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells was evaluated by flow cytometry, RT-PCR and Western blotting. The results showed that allergen-related colitis was induced in mice as shown by heavy infiltration of inflammatory cells in the colon mucosa, loss of body weight of mice, increases in myeloperoxidase, tumor necrosis factor-α, interleukin-4, OVA-specific IgE in the colon tissue. The colon epithelial barrier function was markedly compromised in colitis group mice, which was mimicked by exposure the colon mucosa to CT in Ussing chamber. High frequency of TIM4+ dendritic cells was detected in the colon mucosa of colitis mice. Exposure of dendritic cells to CT markedly increased the expression of TIM4. We conclude that IBD-like inflammation can be induced in the mouse colon by the food allergen-related immune response. PMID:27604348

  3. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet−/− Rag2−/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  4. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    PubMed Central

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  5. Dietary Uptake of Wedelia chinensis Extract Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice

    PubMed Central

    Chen, Yung-Hsiang; Huang, Wen-Ching; Huang, Li-Ting; Lin, Wen-Ching; Arulselvan, Palanisamy; Liao, Jiunn-Wang; Lin, Shu-Hui; Hsiao, Pei-Wen; Kuo, Sheng-Chu; Yang, Ning-Sun

    2013-01-01

    Scope Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. Methods and Results C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice. Conclusion Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease. PMID:23734189

  6. Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis

    PubMed Central

    Feng, Ting; Wang, Lanfang; Schoeb, Trenton R.; Elson, Charles O.

    2010-01-01

    Little is known about how the microbiota regulates T cell proliferation and whether spontaneous T cell proliferation is involved in the pathogenesis of inflammatory bowel disease. In this study, we show that stimulation of innate pathways by microbiota-derived ligands and antigen-specific T cell stimulation are both required for intestinal inflammation. Microbiota-derived ligands promoted spontaneous T cell proliferation by activating dendritic cells (DCs) to produce IL-6 via Myd88, as shown by the spontaneous proliferation of T cells adoptively transferred into specific pathogen–free (SPF) RAG−/− mice, but not in germfree RAG−/− mice. Reconstitution of germfree RAG−/− mice with cecal bacterial lysate–pulsed DCs, but not with IL-6−/− or Myd88−/− DCs, restored spontaneous T cell proliferation. CBir1 TCR transgenic (CBir1 Tg) T cells, which are specific for an immunodominant microbiota antigen, induced colitis in SPF RAG−/− mice. Blocking the spontaneous proliferation of CBir1 Tg T cells by co-transferring bulk OT II CD4+ T cells abrogated colitis development. Although transferred OT II T cells underwent spontaneous proliferation in RAG−/− mice, the recipients failed to develop colitis because of the lack of cognate antigen in the intestinal lumen. Collectively, our data demonstrate that induction of colitis requires both spontaneous proliferation of T cells driven by microbiota-derived innate signals and antigen-specific T cell proliferation. PMID:20498021

  7. European Crohn's and Colitis Organisation Topical Review on Prediction, Diagnosis and Management of Fibrostenosing Crohn's Disease.

    PubMed

    Rieder, Florian; Latella, Giovanni; Magro, Fernando; Yuksel, Elif S; Higgins, Peter D R; Di Sabatino, Antonio; de Bruyn, Jessica R; Rimola, Jordi; Brito, Jorge; Bettenworth, Dominik; van Assche, Gert; Bemelman, Willem; d'Hoore, Andre; Pellino, Gianluca; Dignass, Axel U

    2016-08-01

    This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focused on prediction, diagnosis, and management of fibrostenosing Crohn's disease [CD]. The objective was to achieve evidence-supported, expert consensus that provides guidance for clinical practice. PMID:26928961

  8. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats.

    PubMed

    Nagib, Marwa M; Tadros, Mariane G; ElSayed, Moushira I; Khalifa, Amani E

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5days. OLM-M (1, 3 and 10mg/kg) was administered orally during 21days prior to the induction of colitis, and for 5days after. Sulfasalazine (500mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects.

  9. Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers.

    PubMed

    Duranti, Sabrina; Gaiani, Federica; Mancabelli, Leonardo; Milani, Christian; Grandi, Andrea; Bolchi, Angelo; Santoni, Andrea; Lugli, Gabriele Andrea; Ferrario, Chiara; Mangifesta, Marta; Viappiani, Alice; Bertoni, Simona; Vivo, Valentina; Serafini, Fausta; Barbaro, Maria Raffaella; Fugazza, Alessandro; Barbara, Giovanni; Gioiosa, Laura; Palanza, Paola; Cantoni, Anna Maria; de'Angelis, Gian Luigi; Barocelli, Elisabetta; de'Angelis, Nicola; van Sinderen, Douwe; Ventura, Marco; Turroni, Francesca

    2016-12-01

    Ulcerative colitis (UC) is associated with a substantial alteration of specific gut commensals, some of which may be involved in microbiota-mediated protection. In this study, microbiota cataloging of UC patients by 16S rRNA microbial profiling revealed a marked reduction of bifidobacteria, in particular the Bifidobacterium bifidum species, thus suggesting that this taxon plays a biological role in the aetiology of UC. We investigated this further through an in vivo trial by testing the effects of oral treatment with B. bifidum PRL2010 in a wild-type murine colitis model. TNBS-treated mice receiving 10(9) cells of B. bifidum PRL2010 showed a marked reduction of all colitis-associated histological indices as well as maintenance of mucosal integrity as it was shown by the increase in the expression of many tight junction-encoding genes. The protective role of B. bifidum PRL2010, as well as its sortase-dependent pili, appears to be established through the induction of an innate immune response of the host. These results highlight the importance of B. bifidum as a microbial biomarker for UC, revealing its role in protection against experimentally induced colitis. PMID:27604252

  10. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis

    PubMed Central

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-01-01

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5−/− mice or adoptive transfer of splenic naïve CD4+ T-cells from wild type or CCR5−/− mice into RAG-1−/−. CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4+ and CD11b+ leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs. PMID:27492684

  11. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission.

    PubMed

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan E T; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-07-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet(-/-) Rag2(-/-) mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis.

  12. Prior H. pylori infection ameliorates S. typhimurium induced colitis: mucosal crosstalk between stomach and distal intestine

    PubMed Central

    Higgins, Peter D.R.; Johnson, Laura A.; Luther, Jay; Zhang, Min; Kao, John Y.

    2012-01-01

    Background Helicobacter pylori infection is associated with a lower risk of chronic autoimmune diseases including IBD. H. pylori modulates the gastric immune response, decreasing the local inflammatory response to itself. In mice, chronic Salmonella typhimurium infection induces colitis similar to Crohn’s disease characterized by inflammation which progresses towards fibrosis. The aim of this study was to determine whether prior H. pylori infection acts at a distance to modulate the immune response of S. typhimurium-induced colitis. Methods Mice were infected with the mouse-adapted strain of H. pylori (SS1), followed by infection with S. typhimurium. The effect of H. pylori on colitis was determined by gross pathology, histopathology, cytokine response, and development of fibrosis in the cecum. Gastritis and systemic immune response was measured in response to infection. Results H. pylori suppresses the Th17 response to S. typhimurium infection in the mouse cecum, but does not alter the Th2 or Treg response or the development of fibrosis. H. pylori infection induces IL-10 in the mesenteric lymph nodes, suggesting an extra-gastric mechanism for immunomodulation. H. pylori/S. typhimurium co-infection decreases inflammation in both the cecum and the stomach. Conclusions This study demonstrates a potential mechanism for the negative association between H. pylori and IBD in humans. H. pylori represses the lower gastrointestinal tract Th17 response to bacterially induced colitis via extra-gastric immunomodulatory effects, illustrating immunological crosstalk between the upper and lower gastrointestinal tract. PMID:21560200

  13. Anti-TNF-refractory colitis after checkpoint inhibitor therapy: Possible role of CMV-mediated immunopathogenesis.

    PubMed

    Lankes, Katharina; Hundorfean, Gheorghe; Harrer, Thomas; Pommer, Ansgar J; Agaimy, Abbas; Angelovska, Irena; Tajmir-Riahi, Azadeh; Göhl, Jonas; Schuler, Gerold; Neurath, Markus F; Hohenberger, Werner; Heinzerling, Lucie

    2016-06-01

    Immune-related adverse events (irAEs) induced by checkpoint inhibitors are well known. Since fatal outcomes have been reported early detection and adequate management are crucial. In particular, colitis is frequently observed and can result in intestinal perforation. This is the first report of an autoimmune colitis that was treated according to algorithms but became resistant due to a CMV reactivation. The 32-y-old male patient with metastatic melanoma treated within an anti-PD-1/ipilimumab combination study developed severe immune-mediated colitis (CTCAE grade 3) with up to 18 watery stools per day starting 2 weeks after treatment initiation. After improving upon therapy with immunosuppressive treatment (high dose steroids and infliximab) combined with parenteral nutrition diarrhea again exacerbated. Additionally, the patient had asymptomatic grade 3 CTCAE amylase and lipase elevation. Colitis was monitored by weekly endoscopies and colon biopsies were analyzed histologically with CMV staining, multi-epitope ligand cartography (MELC) and qRT-PCR for inflammatory genes. In the course, CMV reactivation was detected in the colon and treated with antiviral medication in parallel to a reduction of corticosteroids. Subsequently, symptoms improved. The patient showed a complete response for 2 y now including regression of bone metastases. CMV reactivation under checkpoint inhibitor therapy in combination with immunosuppressive treatment for autoimmune side effects has to be considered in these patients and if present treated. Potentially, CMV reactivation is underdiagnosed. Treatment algorithms should include CMV diagnostics.

  14. Brugia malayi abundant larval transcript 2 protein treatment attenuates experimentally-induced colitis in mice.

    PubMed

    Khatri, Vishal; Amdare, Nitin; Yadav, Ravi Shankar; Tarnekar, Aaditya; Goswami, Kalyan; Reddy, Maryada Venkata Rami

    2015-11-01

    Helminths are known to modulate host's immunity by suppressing host protective pro-inflammatory responses. Such immunomodulatory effects have been experimentally shown to have therapeutic implications in immune mediated disorders. In the present study, we have explored a filarial protein i.e. Brugia malayi recombinant abundant larval transcript 2 (rBmALT2) for its therapeutic effect in dextran sodium sulfate (DSS) induced colitis in mouse model. The immunomodulatory activity of rBmALT-2 was initially confirmed by demonstrating that it suppressed the lipopolysaccharide (LPS) induced nitric oxide synthesis and down-regulated the expression of pro-inflammatory cytokines in vitro by peritoneal exudate cells of mice. Treatment with rBmALT2 reduced severity of colitis associated with significant reduction in weight loss, disease activity, colon damage, mucosal edema and histopathological score including myeloperoxidase activity in colon tissues. rBmALT2 was comparatively more effective in attenuation of colitis when used in the preventive mode than when used for curative purpose. The therapeutic effect of rBmALT2 was found to be associated with downregulation of IFN-γ, IL-6, IL-17 and upregulation of IL-10 cytokines. These results provide strong experimental evidence that BmALT2 could be a potential alternative therapeutic agent in colitis. PMID:26669016

  15. Induction of colitis in mice with food allergen-specific immune response.

    PubMed

    Li, Lin-Jing; Zeng, Lu; Li, Xiao-Xi; Mo, Li-Hua; Geng, Xiao-Rui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Feng, Bai-Sui; Yang, Ping-Chang

    2016-01-01

    The pathogenesis of intestinal chronic inflammation is unclear. Food allergy plays an important role in the induction of intestinal inflammation. This study aims to test a hypothesis that food allergy initiates colitis. In this study, BALB/c mice were sensitized to a common food allergen, ovalbumin (OVA) with cholera toxin (CT) as an adjuvant. The colon epithelial barrier function was assessed with Ussing chamber technique. Expression of T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells was evaluated by flow cytometry, RT-PCR and Western blotting. The results showed that allergen-related colitis was induced in mice as shown by heavy infiltration of inflammatory cells in the colon mucosa, loss of body weight of mice, increases in myeloperoxidase, tumor necrosis factor-α, interleukin-4, OVA-specific IgE in the colon tissue. The colon epithelial barrier function was markedly compromised in colitis group mice, which was mimicked by exposure the colon mucosa to CT in Ussing chamber. High frequency of TIM4(+) dendritic cells was detected in the colon mucosa of colitis mice. Exposure of dendritic cells to CT markedly increased the expression of TIM4. We conclude that IBD-like inflammation can be induced in the mouse colon by the food allergen-related immune response. PMID:27604348

  16. Fulminant clostridium difficile colitis: comparing computed tomography with histopathology: are they concordant?

    PubMed

    Felder, Seth I; Larson, Brent; Balzer, Bonnie; Wachsman, Ashley; Haker, Katherine; Fleshner, Phillip; Annamalai, Alagappan; Margulies, Daniel R

    2014-10-01

    A Total abdominal colectomy (TAC) is recommended for fulminant Clostridium difficile colitis (FCDC) because intraoperative assessment of diseased segments is inaccurate. To determine whether computerized tomography (CT) provides an accurate assessment of disease, we examined the concordance between CT and histopathologic colitis distribution in patients undergoing TAC for FCDC. The ileocolon was divided into seven distinct segments. Of 20 patients meeting criteria, the median interval between preoperative CT and TAC was 1.5 days (range, 0 to 23 days), and mortality was 65 per cent. The CT distribution of colitis was pancolitis in 12 patients and segmental in eight. Nine of the 12 patients with CT pancolitis had histologic pancolitis (75% concordance). Four of the eight patients with CT-diagnosed segmental disease had histologic segmental disease (50% concordance). For patients with FCDC, the distribution of colitis on CT agrees with the histopathologic extent of disease in the majority of patients. However, discordance between CT and histologic extent of disease was present in 25 to 50 per cent of patients. Therefore, the recommendation for TAC rather than segmental resection for FCDC remains justified. PMID:25264661

  17. Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

    PubMed Central

    Trivedi, Palak J.; Bruns, Tony; Ward, Stephen; Mai, Martina; Schmidt, Carsten; Hirschfield, Gideon M.; Weston, Chris J.; Adams, David H.

    2016-01-01

    CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4+) and 30% (CD8+) of tissue-infiltrating T-cells in colitis were identified as CCR9+ effector lymphocytes, compared to <10% of T-cells being CCR9+ in normal colon. Sorted CCR9+ lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9– counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver. PMID:26873648

  18. Heligmosomoides induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut Tcell responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunological diseases like inflammatory bowel disease (IBD) are infrequent in less developed countries possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides bakeri (Hb) prevents colitis. It was determined if Hb mediated IBD pro...

  19. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis

    PubMed Central

    Hainzl, Eva; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit

    2015-01-01

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. PMID:26432894

  20. Retrograde spread of 5-aminosalicylic acid enemas in patients with active ulcerative colitis

    SciTech Connect

    Campieri, M.; Lanfranchi, G.A.; Brignola, C.; Bazzocchi, G.; Gionchetti, P.; Minguzzi, M.R.; Cappello, I.P.; Corbelli, C.; Boschi, S.

    1986-02-01

    In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.

  1. Catecholamine Mediates Psychological Stress-Induced Colitis Through a2-Adrenoreceptor.

    PubMed

    Bai, Aiping; Chen, Jiang; Liao, Wangdi; Lu, Nonghua; Guo, Yuan

    2015-07-01

    Psychological stress has long been reported to be linked with the disease activity of patients with inflammatory bowel disease (IBD). However, the mechanisms of psychological stress involved in pathogenesis of IBD are still to be elucidated. We have previously shown that catecholamine participates in progression of acute colitis through a2-adrenoreceptors. The study aimed to explore the pivotal role of catecholamine in psychological stress-induced colitis. The expression of dopamine β-hydroxylase (DBH), the rate-limiting enzyme in regulation of catecholamine synthesis, was induced in colon tissues of mice with restraint stress, indicating the association of catecholamine synthesis with psychological stress. Notably, pretreatment with RX821002, an a2-adrenoceptor antagonist, attenuated inflammatory responses of psychological stress-induced colitis. Intriguingly, DBH levels were elevated in colon tissues of patients with active IBD. The study suggests that a2-adrenoreceptors/catecholamine play pivotal role in psychological stress-induced colitis and might contribute to the development of human IBD. PMID:25867043

  2. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    PubMed

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-08-05

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

  3. Review article: evolutionary advances in the delivery of aminosalicylates for the treatment of ulcerative colitis.

    PubMed

    Cohen, R D

    2006-08-01

    Ulcerative colitis is a chronic and debilitating disease that involves inflammation of the colonic mucosa. Current therapies aim to reduce the symptom burden of ulcerative colitis and maintain disease quiescence. The standard first-line treatment for mild-to-moderate ulcerative colitis is 5-aminosalicylate therapy, which is available in oral and rectal (topical) formulations. While current 5-aminosalicylate formulations are effective in the majority of patients, they are associated with a number of limitations including inconvenient dosing regimens and poor patient acceptability, which may lead to non-compliance with prescribed therapy. A variety of improved delivery mechanisms have been developed in an effort to overcome these limitations. Micropellet formulations and high-dose tablets appear to offer comparable efficacy and tolerability to conventional formulations, although any benefit in terms of long-term patient compliance remains to be proven. Novel methods of delivery, such as those using a combination of hydrophilic and lipophilic matrices, designed to provide once-daily dosing in a high-strength tablet, may offer a significant improvement in the therapy of active and quiescent ulcerative colitis. This review examines the limitations of current 5-aminosalicylate formulations and reports on the evolution of novel oral formulations designed to overcome these limitations, maximize patient compliance during both induction and maintenance of quiescence, and optimize overall clinical outcomes.

  4. Induction of colitis in mice with food allergen-specific immune response

    NASA Astrophysics Data System (ADS)

    Li, Lin-Jing; Zeng, Lu; Li, Xiao-Xi; Mo, Li-Hua; Geng, Xiao-Rui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Feng, Bai-Sui; Yang, Ping-Chang

    2016-09-01

    The pathogenesis of intestinal chronic inflammation is unclear. Food allergy plays an important role in the induction of intestinal inflammation. This study aims to test a hypothesis that food allergy initiates colitis. In this study, BALB/c mice were sensitized to a common food allergen, ovalbumin (OVA) with cholera toxin (CT) as an adjuvant. The colon epithelial barrier function was assessed with Ussing chamber technique. Expression of T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells was evaluated by flow cytometry, RT-PCR and Western blotting. The results showed that allergen-related colitis was induced in mice as shown by heavy infiltration of inflammatory cells in the colon mucosa, loss of body weight of mice, increases in myeloperoxidase, tumor necrosis factor-α, interleukin-4, OVA-specific IgE in the colon tissue. The colon epithelial barrier function was markedly compromised in colitis group mice, which was mimicked by exposure the colon mucosa to CT in Ussing chamber. High frequency of TIM4+ dendritic cells was detected in the colon mucosa of colitis mice. Exposure of dendritic cells to CT markedly increased the expression of TIM4. We conclude that IBD-like inflammation can be induced in the mouse colon by the food allergen-related immune response.

  5. Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.

    PubMed

    Liu, Bo; Lin, Qinlu; Yang, Tao; Zeng, Linna; Shi, Limin; Chen, Yaya; Luo, Feijun

    2015-11-01

    Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors. PMID:26292622

  6. Infliximab: the evidence for its place in therapy in ulcerative colitis

    PubMed Central

    Van Assche, Gert; Vermeire, Séverine; Rutgeerts, Paul

    2007-01-01

    Introduction: Refractory ulcerative colitis has a high, unmet medical need for avoiding steroid dependency and avoiding colectomy. Controlled trials with biologic agents have recently been reported. Aims: We aimed to review the current evidence supporting the use of the monoclonal antitumor necrosis factor antibody, infliximab, in active ulcerative colitis and determine its current place in therapy. Evidence review: Although faced with initial conflicting data particularly in steroid-refractory patients, two large, placebo-controlled trials have shown that intravenous infliximab induces and maintains clinical improvement in a clinically significant proportion of patients when used with scheduled re-treatment. Infliximab also spares steroids and induces endoscopic remission in moderately ill patients. In fulminant colitis unresponsive to intravenous steroids, one placebo-controlled trial indicates that infliximab is able to prevent colectomy in this patient population. Evidence for cost effectiveness and avoidance of colectomy long term are still lacking. Place in therapy: Infliximab 5 mg/kg induction at 0, 2, and 6 weeks, and every 8 weeks thereafter should be considered in patients with moderately to severely active ulcerative colitis failing medical therapy. Steroid-dependent and steroid-refractory patients also qualify for infliximab therapy. PMID:21221182

  7. Vasoactive Intestinal Polypeptide Promotes Intestinal Barrier Homeostasis and Protection Against Colitis in Mice

    PubMed Central

    Wu, Xiujuan; Conlin, Victoria S.; Morampudi, Vijay; Ryz, Natasha R.; Nasser, Yasmin; Bhinder, Ganive; Bergstrom, Kirk S.; Yu, Hong B.; Waterhouse, Chris C. M.; Buchan, Allison M. J.; Popescu, Oana E.; Gibson, William T.; Waschek, James A.; Vallance, Bruce A.; Jacobson, Kevan

    2015-01-01

    Inflammatory bowel disease is a chronic gastrointestinal inflammatory disorder associated with changes in neuropeptide expression and function, including vasoactive intestinal peptide (VIP). VIP regulates intestinal vasomotor and secretomotor function and motility; however, VIP’s role in development and maintenance of colonic epithelial barrier homeostasis is unclear. Using VIP deficient (VIPKO) mice, we investigated VIP’s role in epithelial barrier homeostasis, and susceptibility to colitis. Colonic crypt morphology and epithelial barrier homeostasis were assessed in wildtype (WT) and VIPKO mice, at baseline. Colitic responses were evaluated following dinitrobenzene sulfonic acid (DNBS) or dextran-sodium sulfate (DSS) exposure. Mice were also treated with exogenous VIP. At baseline, VIPKO mice exhibited distorted colonic crypts, defects in epithelial cell proliferation and migration, increased apoptosis, and altered permeability. VIPKO mice also displayed reduced goblet cell numbers, and reduced expression of secreted goblet cell factors mucin 2 and trefoil factor 3. These changes were associated with reduced expression of caudal type homeobox 2 (Cdx2), a master regulator of intestinal function and homeostasis. DNBS and DSS-induced colitis were more severe in VIPKO than WT mice. VIP treatment rescued the phenotype, protecting VIPKO mice against DSS colitis, with results comparable to WT mice. In conclusion, VIP plays a crucial role in the development and maintenance of colonic epithelial barrier integrity under physiological conditions and promotes epithelial repair and homeostasis during colitis. PMID:25932952

  8. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

    PubMed Central

    Vigna, Steven R.

    2016-01-01

    Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID:26881175

  9. Oat β-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.

    PubMed

    Liu, Bo; Lin, Qinlu; Yang, Tao; Zeng, Linna; Shi, Limin; Chen, Yaya; Luo, Feijun

    2015-11-01

    Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors.

  10. Embelin lipid nanospheres for enhanced treatment of ulcerative colitis - Preparation, characterization and in vivo evaluation.

    PubMed

    Badamaranahalli, Shivaram Shivakumar; Kopparam, Manjunath; Bhagawati, Siddalingappa Tippanna; Durg, Sharanbasappa

    2015-08-30

    Aim of the present study is to develop embelin lipid nanospheres (LNE) for better treatment of ulcerative colitis. Embelin LNs were developed using soya bean oil/virgin coconut oil as liquid lipid carrier and soya/egg lecithin as stabilizer by hot homogenization followed by ultrasonication technique. The particle size of LNEs ranged from 196.1±3.57 to 269.2±1.05nm with narrow polydispersity index values whereas zeta potential was from -36.6 to -62.0mV. Embelin was successfully incorporated into lipid nanospheres with entrapment efficiency about 99%. There was no interaction between embelin and selected liquid lipids which was confirmed by FTIR studies. In vitro drug release studies performed using Franz diffusion cell and results showed sustained release of embelin. Embelin LNs were stabilized with egg and soya lecithin, embelin release from these LNs followed Higuchi model and first order model, respectively, however mechanism of drug release in both LNs was non-Fickian. In vivo studies were carried out using acetic acid induced ulcerative colitis rat model and results revealed that treatment with embelin LNs significantly reduced clinical activity and macroscopic scores compared to embelin conventional suspension. Treatment with embelin LNs decreased MPO, LDH and LPO levels, increased reduced GSH levels which indicated better treatment of ulcerative colitis was achieved. This was also confirmed by improved histopathological conditions. Thus embelin LNs could be favourably used for treatment of ulcerative colitis. PMID:25957524

  11. IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis.

    PubMed

    Gerlach, Katharina; McKenzie, Andrew N; Neurath, Markus F; Weigmann, Benno

    2015-01-01

    As previous studies suggested that IL-9 may control intestinal barrier function, we tested the role of IL-9 in experimental T cell-mediated colitis induced by the hapten reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS). The deficiency of IL-9 suppressed TNBS-induced colitis and led to lower numbers of PU.1 expressing T cells in the lamia propria, suggesting a regulatory role for Th9 cells in the experimental TNBS colitis model. Since IL-9 is known to functionally alter intestinal barrier function in colonic inflammation, we assessed the expression of tight junction molecules in intestinal epithelial cells of TNBS-inflamed mice. Therefore we made real-time PCR analyses for tight junction molecules in the inflamed colon from wild-type and IL-9 KO mice, immunofluorescent stainings and investigated the expression of junctional proteins directly in intestinal epithelial cells of TNBS-inflamed mice by Western blot studies. The results demonstrated that sealing proteins like occludin were up regulated in the colon of inflamed IL-9 KO mice. In contrast, the tight junction protein Claudin1 showed lower expression levels when IL-9 is absent. Surprisingly, the pore-forming molecule Claudin2 revealed equal expression in TNBS-treated wild-type and IL-9-deficient animals. These results illustrate the pleiotropic functions of IL-9 in changing intestinal permeability in experimental colitis. Thus, modulation of IL-9 function emerges as a new approach for regulating barrier function in intestinal inflammation.

  12. The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis.

    PubMed

    Kato, Masayoshi; Marumo, Masaya; Nakayama, Jun; Matsumoto, Misaki; Yabe-Nishimura, Chihiro; Kamata, Tohru

    2016-07-29

    Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1-deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis. PMID:26876598

  13. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis.

    PubMed

    Wei, Pijin; Yang, Yan; Liu, Zhaobing; Huang, Junli; Gong, Yahui; Sun, Hanxiao

    2016-07-01

    The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy. PMID:26673899

  14. Panax notoginseng attenuates experimental colitis in AOM/DSS mouse model

    PubMed Central

    Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhao, Lei; Zhang, Zhiyu; Matin, Adiba; Wang, Yunwei; Li, Ping; Xiao, Shu-Yuan; Du, Wei; He, Tong-Chuan; Yuan, Chun-Su

    2013-01-01

    Patients suffering from inflammatory bowel disease are at a high risk of developing colorectal cancer. To assess the anti-cancer potential of botanicals, in this study, we evaluated the effects of Panax notoginseng on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis. One week after A/J mice received AOM, the animals received DSS for 8 days, or were supplemented with P. notoginseng extract, at 30 or 90 mg/kg. DSS-induced colitis was scored with the disease activity index (DAI). The severity of the inflammatory lesions was evaluated by a colon tissue histological assessment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also explored. We observed that the effects of P. notoginseng on the reduction of colon inflammation, expressed in DAI score, were in a dose-related manner (P < 0.01). P. notoginseng inhibited the reduction of the colon length and the loss of bodyweight in dose-related manner (all P < 0.05). The histological assessment of the colitis and inflammatory related immunohistochemical data also supported the pharmacological observations. Our data suggest that P. notoginseng is a promising candidate in preventing and treating colitis and inflammation-associated colon carcinogenesis. PMID:24142591

  15. Helogmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL10-/- T cell transfer model of colitis, Heligmosomoides polygyrus (Hp), an intestinal hel...

  16. Ulcerative colitis and a bleeding polyp detected on Tc-99m-pertechnetate abdominal scintigraphy

    SciTech Connect

    Howman-Giles, R.

    1981-10-01

    Two children with rectal bleeding were diagnosed as having ulcerative colitis and a bleeding colonic polyp respectively using abdominal scanning with Tc-99m pertechnetate. Early flow studies are recommended with careful attention paid to the amount of time abnormal areas of activity are seen on the abdominal scan.

  17. The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis

    PubMed Central

    Kato, Masayoshi; Marumo, Masaya; Nakayama, Jun; Matsumoto, Misaki; Yabe-Nishimura, Chihiro; Kamata, Tohru

    2016-01-01

    Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1-deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis. PMID:26876598

  18. Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis.

    PubMed

    Yu, Changhui; Zhang, Su; Song, Lei; Wang, Yusheng; Hwaiz, Rundk; Luo, Lingtao; Thorlacius, Henrik

    2014-10-15

    Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils. Administration of NSC23766 decreased DSS-induced neutrophil recruitment and tissue damage in the colon. Rac1 inhibition decreased colonic formation of IL-6 and CXC chemokines in experimental colitis. Chemokine challenge increased Rac1 activity in neutrophils and NSC23766 markedly reduced this neutrophil activity of Rac1. Inhibition of Rac1 abolished CXC chemokine-induced neutrophil chemotaxis and up-regulation of Mac-1 in vitro. Taken together, Rac1 signaling plays a significant role in controlling accumulation of neutrophils and tissue injury in experimental colitis. Thus, our novel results suggest that targeting Rac1 signaling might be a useful way to protect against neutrophil-mediated tissue injury in acute colitis.

  19. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Okon, E; Bursztyn, M

    1995-01-01

    Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two

  20. Laboratory markers in ulcerative colitis: Current insights and future advances.

    PubMed

    Cioffi, Michele; Rosa, Antonella De; Serao, Rosalba; Picone, Ilaria; Vietri, Maria Teresa

    2015-02-15

    Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of inflammatory bowel diseases (IBD) in man. Despite some common features, these forms can be distinguished by different genetic predisposition, risk factors and clinical, endoscopic and histological characteristics. The aetiology of both CD and UC remains unknown, but several evidences suggest that CD and perhaps UC are due to an excessive immune response directed against normal constituents of the intestinal bacterial flora. Tests sometimes invasive are routine for the diagnosis and care of patients with IBD. Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations. The employment of non-invasive biomarkers is needed. These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications. The ability to determine the type, severity, prognosis and response to therapy of UC, using biomarkers has long been a goal of clinical researchers. We describe the biomarkers assessed in UC, with special reference to acute-phase proteins and serologic markers and thereafter, we describe the new biological markers and the biological markers could be developed in the future: (1) serum markers of acute phase response: The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate. Other biomarkers of inflammation in UC include platelet count, leukocyte count, and serum albumin and serum orosomucoid concentrations; (2) serologic markers/antibodies: In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies. In UC, the presence of these antibodies can aid as surrogate markers for the aberrant host immune response; and (3) future biomarkers: The development of biomarkers in UC will be very

  1. Parameters of a severe disease course in ulcerative colitis

    PubMed Central

    Stallmach, Andreas; Nickel, Luisa; Lehmann, Thomas; Bokemeyer, Bernd; Bürger, Martin; Hüppe, Dietrich; Kruis, Wolfgang; Nikolaus, Susanna; Preiss, Jan C; Sturm, Andreas; Teich, Niels; Schmidt, Carsten

    2014-01-01

    AIM: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT). METHODS: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy. RESULTS: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can

  2. Laboratory markers in ulcerative colitis: Current insights and future advances.

    PubMed

    Cioffi, Michele; Rosa, Antonella De; Serao, Rosalba; Picone, Ilaria; Vietri, Maria Teresa

    2015-02-15

    Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of inflammatory bowel diseases (IBD) in man. Despite some common features, these forms can be distinguished by different genetic predisposition, risk factors and clinical, endoscopic and histological characteristics. The aetiology of both CD and UC remains unknown, but several evidences suggest that CD and perhaps UC are due to an excessive immune response directed against normal constituents of the intestinal bacterial flora. Tests sometimes invasive are routine for the diagnosis and care of patients with IBD. Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations. The employment of non-invasive biomarkers is needed. These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications. The ability to determine the type, severity, prognosis and response to therapy of UC, using biomarkers has long been a goal of clinical researchers. We describe the biomarkers assessed in UC, with special reference to acute-phase proteins and serologic markers and thereafter, we describe the new biological markers and the biological markers could be developed in the future: (1) serum markers of acute phase response: The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate. Other biomarkers of inflammation in UC include platelet count, leukocyte count, and serum albumin and serum orosomucoid concentrations; (2) serologic markers/antibodies: In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies. In UC, the presence of these antibodies can aid as surrogate markers for the aberrant host immune response; and (3) future biomarkers: The development of biomarkers in UC will be very

  3. CXCR4 Antagonist AMD3100 Modulates Claudin Expression and Intestinal Barrier Function in Experimental Colitis

    PubMed Central

    Xia, Xian-Ming; Wang, Fang-Yu; Zhou, Ju; Hu, Kai-Feng; Li, Su-Wen; Zou, Bing-Bing

    2011-01-01

    Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of colonic claudin-1, claudin-3, claudin-5, claudin-7 and claudin-8 were markedly decreased after DSS administration, whereas colonic claudin-2 expression was significantly decreased. Treatment with AMD3100 prevented all these changes. However, AMD3100 had no influence on claudin-3, claudin-5, claudin-7 and claudin-8 expression in HT-29/B6 cells. Cytokines as TNF-α, IL-6, and IFN-γ increased apoptosis and monolayer permeability, inhibited the wound-healing and the claudin-3, claudin-7 and claudin-8 expression in HT-29/B6 cells. We suggest that AMD3100 acted on colonic claudin expression and intestinal barrier function, at least partly, in a cytokine-dependent pathway. PMID:22073304

  4. Single Nucleotide Polymorphisms that Increase Expression of the GTPase RAC1 are Associated with Ulcerative Colitis

    PubMed Central

    Muise, Aleixo M; Walters, Thomas; Xu, Wei; Shen-Tu, Grace; Guo, Cong-Hui; Fattouh, Ramzi; Lam, Grace Y; Wolters, Victorien M; Bennitz, Joshua; Van Limbergen, Johan; Renbaum, Paul; Kasirer, Yair; Ngan, Bo-Yee; Turner, Dan; Denson, Lee A; Sherman, Philip M; Duerr, Richard H; Cho, Judy; Lees, Charlie W; Satsangi, Jack; Wilson, David C; Paterson, Andrew D; Griffiths, Anne M; Glogauer, Michael; Silverberg, Mark S; Brumell, John H

    2011-01-01

    Background & Aims RAC1 is a GTPase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases (IBD) are associated with dysregulation of immune defenses. We studied the role of RAC1 in IBD using human genetic and functional studies and animal models of colitis. Methods We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms (SNPs) in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 mRNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulphate sodium (DSS). Results We observed a genetic association between RAC1 with ulcerative colitis (UC) in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the SNPs rs10951982 (Pcombined UC = 3.3 × 10–8, odds ratio [OR]=1.43 [1.26–1.63]) and rs4720672 (Pcombined UC=4.7 × 10–6, OR=1.36 [1.19–1.58]). Patients with IBD who had the rs10951982 risk allele had increased expression of RAC1, compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected them against DSS-induced colitis. Conclusion Studies of human tissue samples and knockout mice demonstrated a role for the GTPase RAC1 in the development of UC; increased expression of RAC1 was associated with susceptibility to colitis. PMID:21684284

  5. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

    PubMed

    Reyes, José L; Fernando, Maria R; Lopes, Fernando; Leung, Gabriella; Mancini, Nicole L; Matisz, Chelsea E; Wang, Arthur; McKay, Derek M

    2016-04-01

    Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host. PMID:27055194

  6. Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

    PubMed Central

    Barollo, Michela; Medici, Valentina; D’Incà, Renata; Banerjee, Antara; Ingravallo, Giuseppe; Scarpa, Marco; Patak, Surajit; Ruffolo, Cesare; Cardin, Romilda; Sturniolo, Giacomo Carlo

    2011-01-01

    AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The experimental mice were then randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham control animals. Macroscopic and histological features were scored blindly. Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc. The effect was more pronounced in the latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P < 0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs controls, P < 0.05), were significantly reduced in the treated groups, with a more remarkable effect in the group receiving combined therapy (vs standard diet, P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity. PMID:22039323

  7. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

    PubMed Central

    Reyes, José L.; Fernando, Maria R.; Lopes, Fernando; Leung, Gabriella; Mancini, Nicole L.; Matisz, Chelsea E.; Wang, Arthur; McKay, Derek M.

    2016-01-01

    Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host. PMID:27055194

  8. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    SciTech Connect

    Nagib, Marwa M.; Tadros, Mariane G.; ELSayed, Moushira I.; Khalifa, Amani E.

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  9. Mangiferin attenuates DSS colitis in mice: Molecular docking and in vivo approach.

    PubMed

    Somani, Sahil; Zambad, Shitalkumar; Modi, Ketan

    2016-06-25

    Inflammation, oxidative stress and altered mucosal barrier permeability are potential etiopathological or triggering factors for inflammatory bowel disease (IBD). In this study, the therapeutic potential of Mangiferin was investigated in vivo in mouse model of colitis and also attempts were made to understand mechanistic insights of Mangiferin in IBD. In present study, colitis was induced by administration of 5% DSS for 11 days, followed by 3 days of DSS free period. On day 14, animals were sacrificed and colon tissues were taken for biochemical and histological analysis. Therapeutic treatment with Mangiferin after colitis induction (i.e. day 5) ameliorated symptoms of colitis (presence of blood in stools, body weight loss and diarrhea) as evidenced by reduced DAI score, attenuated the levels of catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO). It also decreased the colonic pro-inflammatory mediators tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) levels, matrix metalloproteinase-9 (MMP-9) activity and histopathological score. Molecular docking of Mangiferin against TNF-α and MMP-9 was evaluated using GLIDE software. Mangiferin demonstrated the glide score of -8.04 kcal/mol for TNF-α and -9.97 kcal/mol for MMP-9, which indicated its binding potential with TNF-α and MMP-9. In conclusion, Mangiferin reduces colonic damage in a murine model of colitis, alleviates the oxidative and inflammatory events partly through directly influencing the activity of TNF-α and MMP-9 and therefore might have therapeutic usefulness in the management of inflammatory bowel disease.

  10. IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression.

    PubMed

    Reyes, José L; Fernando, Maria R; Lopes, Fernando; Leung, Gabriella; Mancini, Nicole L; Matisz, Chelsea E; Wang, Arthur; McKay, Derek M

    2016-04-01

    Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

  11. Collagenous gastritis.

    PubMed

    Colletti, R B; Trainer, T D

    1989-12-01

    Subepithelial fibrosis has previously been reported in the small intestine (collagenous sprue) and colon (collagenous colitis). We report a 15-yr-old girl with chronic gastritis and subepithelial fibrosis of the gastric corpus who presented with recurrent abdominal pain and acute upper gastrointestinal bleeding. Nodularity and erythema of the gastric corpus were persistent endoscopic findings. Biopsies revealed patchy chronic active gastritis with a striking focal thick band of collagen immediately beneath the surface epithelial cells that did not extend to deeper portions of the lamina propria. Contrast radiography demonstrated an abnormal mucosa of the gastric corpus with a mosaiclike surface pattern. Numerous studies have failed to elucidate the etiology. Despite treatment with ranitidine, sucralfate, and furazolidone, there has been no clinical or pathologic improvement. The pathogenesis and prognosis of collagenous gastritis, and its relationship to collagenous sprue and collagenous colitis, remain to be defined. PMID:2583419

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

    PubMed

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

    2015-04-01

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

  13. Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBD

    PubMed Central

    Brenna, Øystein; Furnes, Marianne W.; Drozdov, Ignat; van Beelen Granlund, Atle; Flatberg, Arnar; Sandvik, Arne K.; Zwiggelaar, Rosalie T. M.; Mårvik, Ronald; Nordrum, Ivar S.; Kidd, Mark; Gustafsson, Björn I.

    2013-01-01

    Background Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD. Methodology/Principal Findings Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing. Conclusions/Significance Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene

  14. Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta: involvement of IL-5 and eosinophils.

    PubMed

    Wang, Arthur; Fernando, Maria; Leung, Gabriella; Phan, Van; Smyth, David; McKay, Derek M

    2010-12-01

    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.

  15. Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice.

    PubMed

    Zhang, Yinzhong; Brenner, Max; Yang, Weng-Lang; Wang, Ping

    2015-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive system and typically requires lifelong medical care. Recombinant human MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell clearance and reduces inflammation. This study investigates the therapeutic effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or 120 μg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. Treatment of DSS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 97%, the colitis severity score by 82%, and colon shrinkage by 62% when compared with vehicle. In both models, the colons of animals receiving rhMFG-E8 showed marked reduction in neutrophil infiltration, cytokine and chemokine expression, and apoptotic cell counts. In conclusion, rhMFG-E8 ameliorates DSS- and TNBS-induced colitis, suggesting that it has the potential to become a novel therapeutic agent for IBD.

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

    PubMed

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

    2014-09-01

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

  17. T cell transfer model of colitis: a great tool to assess the contribution of T cells in chronic intestinal inflammation.

    PubMed

    Eri, Rajaraman; McGuckin, Michael A; Wadley, Robert

    2012-01-01

    Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC) affecting about 0.1% of the western population. These two chronic gut diseases affect youth at their prime of life causing diarrhoea, intestinal bleeding, and severe gut discomfort. Mouse models of colitis have been major tools in understanding the pathogenesis of IBD. A number of mouse models are available to assess the contribution of T cells in the pathogenesis of CD and UC. Among these, the T cell transfer model of colitis is the most widely used model to dissect the initiation, induction, and regulation of immunopathology in chronic colitis mediated by T cells. The methodology below describes the classification of various animal models and explains the T cell transfer model in detail, including flow cytometry-based isolation of naïve T cells that are used in the transfer, immunological concepts, detailed immune-pathological assessment, shortcomings of the model, and the latest improvements to this colitis model. A special focus is paid to the utilisation of the T cell transfer model in delineating the immunopathology in a primary epithelial defect model of colitis, namely Winnie. PMID:22262449

  18. Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model

    PubMed Central

    Xiong, Yongjian; Wang, Jingyu; Chu, Hongwei; Chen, Dapeng; Guo, Huishu

    2016-01-01

    Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease. PMID:27303297

  19. Comparative Protective Effect of Hawthorn Berry Hydroalcoholic Extract, Atorvastatin, and Mesalamine on Experimentally Induced Colitis in Rats

    PubMed Central

    Shafie-Irannejad, Vahid; Hobbenaghi, Rahim; Tabatabaie, Seyed Hamed; Moshtaghion, Seyed-Mehdi

    2013-01-01

    Abstract The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)–induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration. PMID:23875899

  20. Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.

    PubMed

    Vu, John P; Million, Mulugeta; Larauche, Muriel; Luong, Leon; Norris, Joshua; Waschek, James A; Pothoulakis, Charalabos; Pisegna, Joseph R; Germano, Patrizia M

    2014-01-01

    VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n = 22), PG 97-269 (n = 9), or vehicle (n = 31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP(-/-) mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 μM) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1ϐ, TNF-α, and IL-6 was significantly lower in VIP(-/-) and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases.

  1. Successful treatment of idiopathic colitis related to XIAP deficiency with allo-HSCT using reduced-intensity conditioning.

    PubMed

    Tsuma, Yusuke; Imamura, Toshihiko; Ichise, Eisuke; Sakamoto, Kenichi; Ouchi, Kazutaka; Osone, Shinya; Ishida, Hiroyuki; Wada, Taizo; Hosoi, Hajime

    2015-02-01

    Recently, it has been reported that Crohn's-like intractable colitis occurred in approximately 20% of the patients with XIAP deficiency, also known as X-linked lymphoproliferative disease type 2. Because treatment used for Crohn's disease is not always effective for Crohn's-like colitis related to XIAP deficiency, more effective treatment should be established. Although several studies reported allo-HSCT might be promising even for Crohn's-like colitis related to XIAP deficiency, the outcome of allo-HSCT using MAC for XIAP deficiency is extremely poor due to frequent TRM. In addition, there is little information about the outcome of allo-HSCT for intractable colitis related to XIAP deficiency. Herein, we describe a patient with intractable colitis related to XIAP deficiency who was successfully treated with allo-HSCT using a reduced-intensity conditioning regimen. Although allo-HSCT using the RIC regimen might be a curative therapeutic option for intractable colitis with XIAP deficiency, the prognostic factors that will determine the success of allo-HSCT require further clinical information of more patients.

  2. Adoptive transfer of helminth antigen-pulsed dendritic cells protects against the development of experimental colitis in mice.

    PubMed

    Matisz, Chelsea E; Leung, Gabriella; Reyes, Jose Luis; Wang, Arthur; Sharkey, Keith A; McKay, Derek M

    2015-11-01

    Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO), and RAG-1 KO mice, and the impact on dinitrobenzene sulphonic acid (DNBS)-induced colitis and splenic cytokine production assessed 72 h later. Mice receiving HD-DCs were significantly protected from DNBS-induced colitis and of the experimental groups only these mice displayed increased Th2 cytokines and IL-10 production. Adoptive transfer of HD-DCs protected neither RAG-1 nor IL-10 KO mice from DNBS-colitis. Furthermore, the transfer of CD4(+) splenocytes from recipients of HD-DCs protected naïve mice against DNBS-colitis, in an IL-10 dependent manner. Thus, HD-DCs are a novel anti-colitic immunotherapy that can educate anti-colitic CD4(+) T cells: mechanistically, the anti-colitic effect of HD-DCs requires that the host has an adaptive immune response and the ability to mobilize IL-10.

  3. Social stress-enhanced severity of Citrobacter rodentium induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri

    PubMed Central

    Mackos, Amy R.; Galley, Jeffrey D.; Eubank, Timothy D.; Easterling, Robert S.; Parry, Nicola M.; Fox, James G.; Lyte, Mark; Bailey, Michael T.

    2015-01-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2−/− mice, indicating the effects of the stressor are CCL2-dependent. Additionally, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon, and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through a down-regulation of the chemokine CCL2. PMID:26422754

  4. β-Arrestin2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis.

    PubMed

    Zeng, L X; Tao, J; Liu, H L; Tan, S W; Yang, Y D; Peng, X J; Liu, Z H; Jiang, J; Wu, B

    2015-05-01

    β-Arrestins (β-arrs) are regulators and mediators of G protein-coupled receptor signaling, and accumulating evidence suggests that they are functionally involved in inflammation and autoimmune diseases. However, the effect of β-arrs is unclear in inflammatory bowel disease (IBD), and the role of β-arr2 is unknown in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study is to investigate whether β-arr2 encourages inflammation-induced epithelial apoptosis through endoplasmic reticulum (ER) stress/p53-upregulated modulator of apoptosis (PUMA) in colitis. In the present study, the results showed that β-arr2 was increased in specimens from patients with UC or CD. Furthermore, a β-arr2 deficiency significantly repressed intestinal inflammation, ameliorated colitis, and alleviated mucosal apoptosis in mice. In addition, the targeted deletion of β-arr2 depressed ER stress, inhibited PUMA, and downregulated PUMA-mediated mitochondrial apoptotic signaling in colitis. β-Arr2, an important modulator of G protein-coupled receptor function, binds eIF2α to activate ER stress signaling. Furthermore, the knockdown of PUMA dramatically prevented β-arr2-induced apoptosis via alleviating ER stress in vitro. The results suggest that β-arr2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis and that β-arr2 is a potential therapeutic target for colitis.

  5. Salvianolic Acid B Restored Impaired Barrier Function via Downregulation of MLCK by microRNA-1 in Rat Colitis Model.

    PubMed

    Xiong, Yongjian; Wang, Jingyu; Chu, Hongwei; Chen, Dapeng; Guo, Huishu

    2016-01-01

    Salvianolic acid B (Sal B) is isolated from the traditional Chinese medical herb Salvia miltiorrhiza and is reported to have a wide range of therapeutic benefits. The aim of this study was to investigate the effects of Sal B on epithelial barrier dysfunction in rat colitis and to uncover related mechanisms. Rat colitis model was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The intestinal barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in vitro respectively. The protein expression related to intestinal barrier function was studied using western blotting. The effects of Sal B on inflammatory responses, oxidative damage and colitis recurrence were also studied in this study. The intestinal barrier dysfunction in colitis was reversed by Sal B, accompanied with the decrease of tight junction proteins, and the effect could be blocked by microRNA-1(miR-1) inhibition. The inflammatory responses, oxidative damage and colitis recurrence were also decreased by Sal B. The colitis symptoms and recurrences were ameliorated by Sal B, and restoration of impaired barrier function via downregulation of MLCK by miR-1 maybe involved in this effect. This study provides some novel insights into both of the pathological mechanisms and treatment alternatives of inflammatory bowel disease. PMID:27303297

  6. Fumigaclavine C, an fungal metabolite, improves experimental colitis in mice via downregulating Th1 cytokine production and matrix metalloproteinase activity.

    PubMed

    Wu, Xue-Feng; Fei, Ming-Jian; Shu, Ren-Geng; Tan, Ren-Xiang; Xu, Qiang

    2005-09-01

    In the present paper, the effect of Fumigaclavine C, a fungal metabolite, on experimental colitis was examined. Fumigaclavine C, when administered intraperitoneally once a day, significantly reduced the weight loss and mortality rate of mice with experimental colitis induced by intrarectally injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). This compound also markedly alleviated the macroscopic and microscopic appearances of colitis. Furthermore, Fumigaclavine C, given both in vivo and in vitro, showed a marked inhibition on the expression of several inflammatory cytokines, including IL-1beta, IL-2, IL-12alpha, IFN-gamma, TNF-alpha as well as MMP-9 in sacral lymph node cells, colonic patch lymphocytes and colitis tissues from the TNBS colitis mice. Meanwhile, the compound caused a dose-dependent reduction in IL-2 and IFN-gamma from the lymphocytes at the protein level and MMP-9 activity. These results suggest that Fumigaclavine C may alleviate experimental colitis mainly via down-regulating the production of Th1 cytokines and the activity of matrix metalloproteinase. PMID:16023606

  7. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance

    PubMed Central

    1996-01-01

    In previous studies we showed that a chronic colitis associated with a Th1 T cell response can be induced by the rectal administration of the haptenizing reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). We report here that oral administration of haptenized colonic proteins (HCP) before rectal administration of TNBS effectively suppresses the ability of the latter to induce colitis. This suppression (oral tolerance) appears to be due to the generation of mucosal T cells producing TGF-beta and Th2-type cytokines after oral HCP administration. Peyer's patch and lamina propria CD4+ T cells from HCP- fed animals stimulated with anti-CD3/anti-CD28 had a 5-10-fold increase in their production of TGF-beta and secreted increased amounts of IL-4 and IL-10 but lower levels of IFN-gamma in comparison to T cells from ovalbumin-fed control animals. In addition, the colons of HCP-fed mice showed strikingly increased TGF-beta but decreased IL-12 expression by immunohistochemical studies and isolated mononuclear cells from HCP-fed animals secreted less IL-12 heterodimer. Finally, and most importantly, the suppressive effect of orally administered HCP was abrogated by the concomitant systemic administration of anti-TGF-beta or rIL-12 suggesting a reciprocal relationship between IL-12 and TGF-beta on tolerance induction in TNBS-induced colitis. In parallel studies we demonstrated that TNBS-induced colitis can be transferred to naive recipient animals with purified CD4+ T cells from the colon of TNBS- treated animals and that such animals develop lethal pancolitis when exposed to very low doses of TNBS. Feeding of HCP suppressed this sensitivity to TNBS, indicating that oral feeding can suppress the response of pre-committed T cells in vivo. These studies suggest for the first time that TGF-beta production can abrogate experimental granulomatous colitis even after such colitis is established, and thus, that regulation of TGF-beta levels may have relevance to the treatment of human

  8. Collagenous gastroduodenitis.

    PubMed

    Rustagi, Tarun; Rai, Mridula; Scholes, John V

    2011-10-01

    Collagenous gastroduodenitis is a rare histopathologic entity characterized by marked subepithelial collagen deposition with associated mucosal inflammatory infiltrate. Only 4 cases have been reported, of which 3 had associated collagenous colitis. Collagenous gastroduodenitis without colonic involvement is exceptionally rare with only 1 case reported so far in the literature. We present a case of a 68-year-old woman with dyspepsia and mild anemia, who was found to have nodular gastric and duodenal mucosa on endoscopic examination. Histopathology showed collagenous gastroduodenitis. To the best of our knowledge, this is the second (and first in English literature) reported case of isolated collagenous gastroduodenitis.

  9. Collagenous gastroduodenitis.

    PubMed

    Rustagi, Tarun; Rai, Mridula; Scholes, John V

    2011-10-01

    Collagenous gastroduodenitis is a rare histopathologic entity characterized by marked subepithelial collagen deposition with associated mucosal inflammatory infiltrate. Only 4 cases have been reported, of which 3 had associated collagenous colitis. Collagenous gastroduodenitis without colonic involvement is exceptionally rare with only 1 case reported so far in the literature. We present a case of a 68-year-old woman with dyspepsia and mild anemia, who was found to have nodular gastric and duodenal mucosa on endoscopic examination. Histopathology showed collagenous gastroduodenitis. To the best of our knowledge, this is the second (and first in English literature) reported case of isolated collagenous gastroduodenitis. PMID:21346601

  10. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.

    PubMed

    Wang, L; Ray, A; Jiang, X; Wang, J-y; Basu, S; Liu, X; Qian, T; He, R; Dittel, B N; Chu, Y

    2015-11-01

    Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10(-/-) B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis.

  11. T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis

    PubMed Central

    Wang, L; Ray, A; Jiang, X; Wang, J-y; Basu, S; Liu, X; Qian, T; He, R; Dittel, B N; Chu, Y

    2015-01-01

    Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10−/− B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis. PMID:25807185

  12. Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature

    PubMed Central

    Sarlos, Patricia; Kovesdi, Erzsebet; Magyari, Lili; Banfai, Zsolt; Szabo, Andras; Javorhazy, Andras; Melegh, Bela

    2014-01-01

    Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility. PMID:25133031

  13. Acute ischemic colitis during scuba diving: report of a unique case.

    PubMed

    Goumas, Konstantinos; Poulou, Androniki; Tyrmpas, Ioannis; Dandakis, Dimitrios; Bartzokis, Stavros; Tsamouri, Magdalini; Barbati, Kalipso; Soutos, Dimitrios

    2008-05-28

    The presentation of clinical symptoms due to decompression during diving, varies significantly, as mainly minor disturbances for the gastrointestinal tract in particular have been reported. The following case debates whether diving can cause severe symptoms from the gastrointestinal system. We describe a clinical case of ischemic colitis presented in a 27-year-old male, who manifested abdominal pain while in the process of scuba diving 20 meters undersea, followed by bloody diarrhoea as soon as he ascended to sea level. Taking into account his past medical history, the thorough, impeccable clinical and laboratory examinations and presence of no other factors predisposing to ischemia of the colon, we assume that a possible relationship between diving conditions and the pathogenesis of ischemic colitis may exist. This unusual case might represent a hematologic manifestation of decompression sickness, due to increased coagulability and/or transient air emboli, occurring during a routine scuba diving ascent to sea level.

  14. Predictive factors for a severe clinical course in ulcerative colitis: Results from population-based studies.

    PubMed

    Wanderås, Magnus Hofrenning; Moum, Bjørn A; Høivik, Marte Lie; Hovde, Øistein

    2016-05-01

    Ulcerative colitis (UC) is characterized by chronic inflammation of the large bowel in genetically susceptible individuals exposed to environmental risk factors. The disease course can be difficult to predict, with symptoms ranging from mild to severe. There is no generally accepted definition of severe UC, and no single outcome is sufficient to classify a disease course as severe. There are several outcomes indicating a severe disease course, including progression of the disease's extension, a high relapse rate, the development of acute severe colitis, colectomy, the occurrence of colorectal cancer and UC-related mortality. When evaluating a patient's prognosis, it is helpful to do so in relation to these outcomes. Using these outcomes also makes it easier to isolate factors predictive of severe disease. The aims of this article are to evaluate different disease outcomes and to present predictive factors for these outcomes. PMID:27158539

  15. Predictive factors for a severe clinical course in ulcerative colitis: Results from population-based studies

    PubMed Central

    Wanderås, Magnus Hofrenning; Moum, Bjørn A; Høivik, Marte Lie; Hovde, Øistein

    2016-01-01

    Ulcerative colitis (UC) is characterized by chronic inflammation of the large bowel in genetically susceptible individuals exposed to environmental risk factors. The disease course can be difficult to predict, with symptoms ranging from mild to severe. There is no generally accepted definition of severe UC, and no single outcome is sufficient to classify a disease course as severe. There are several outcomes indicating a severe disease course, including progression of the disease’s extension, a high relapse rate, the development of acute severe colitis, colectomy, the occurrence of colorectal cancer and UC-related mortality. When evaluating a patient’s prognosis, it is helpful to do so in relation to these outcomes. Using these outcomes also makes it easier to isolate factors predictive of severe disease. The aims of this article are to evaluate different disease outcomes and to present predictive factors for these outcomes. PMID:27158539

  16. Passage of a sigmoid colon cast in a patient with ischemic colitis.

    PubMed

    Abe, Shinya; Yamaguchi, Hironori; Murono, Koji; Kanazawa, Takamitsu; Ishihara, Souichirou; Sunami, Eiji; Watanabe, Toshiaki

    2014-01-01

    Colon cast passage, which is the spontaneous passage of a full-thickness, infarcted colonic segment per rectum, is a rare occurrence. The main cause is acute ischemic colitis resulting from a circulation compromise. Most of the colon cast cases reported were secondary to abdominal aortic aneurysm repairs or colorectal surgery. We report a case of an 80-year-old woman with ischemic colitis who excreted a 20-cm colon cast. In most cases that involve a colon cast containing a muscle layer component, invasive therapy is required owing to colonic obstruction or stenosis. However, in the present case, the colon cast consisted only of a mucosa layer and was not associated with severe stenosis or obstruction; therefore, it was successfully treated by conservative therapy. Histologic examination of the colon segment may be crucial in determining the appropriate treatment.

  17. Ischaemic colitis in the experimental animal. II. Role of hypovolaemia in the production of the disease.

    PubMed Central

    Matthews, J G; Parks, T G

    1976-01-01

    Hypovolaemia alone did not lead to ischaemic colitis but when venesection was induced immediately after the acute ligation of the common colic artery large bowel ischaemia ensued. Similarly, hypovolaemia induced one month after two major blood vessels had been occluded led to ischaemic colitis. These findings suggest that states of low blood flow in the presence of previous arterial constriction or blockage may lead to enough reduction in mesenteric perfusion for intestinal ischaemia to develop. Using an electromagnetic flowmeter placed in the cranial mesenteric artery of the dog, it was shown that hypovolaemia may lead to 50-75% reduction in mesenteric blood flow without producing any significant change in the systemic blood pressure. Images Fig. 5 Fig. 6 Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:976807

  18. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

    PubMed Central

    Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Sören; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; Barrett, J; de Lange, K; Edwards, C; Hart, A; Hawkey, C; Jostins, L; Kennedy, N; Lamb, C; Lee, J; Lees, C; Mansfield, J; Mathew, C; Mowatt, C; Newman, W; Nimmo, E; Parkes, M; Pollard, M; Prescott, N; Randall, J; Rice, D; Satsangi, J; Simmons, A; Tremelling, M; Uhlig, H; Wilson, D; Abraham, C; Achkar, J.P; Bitton, A; Boucher, G; Croitoru, K; Fleshner, P; Glas, J; Kugathasan, S; Limbergen, J.V; Milgrom, R; Proctor, D; Regueiro, M; Schumm, P.L; Sharma, Y; Stempak, J.M; Targan, S.R; Wang, M.H; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H; Palotie, Aarno; Saavalainen, Päivi; Kontula, Kimmo; Färkkilä, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J.; Barrett, J.; de Lane, K.; Edwards, C.; Hart, A.; Hawkey, C.; Jostins, L.; Kennedy, N.; Lamb, C.; Lee, J.; Lees, C.; Mansfield, J.; Mathew, C.; Mowatt, C.; Newman, B.; Nimmo, E.; Parkes, M.; Pollard, M.; Prescott, N.; Randall, J.; Rice, D.; Satsangi, J.; Simmons, A.; Tremelling, M.; Uhlig, H.; Wilson, D.; Abraham, C.; Achkar, J. P.; Bitton, A.; Boucher, G.; Croitoru, K.; Fleshner, P.; Glas, J.; Kugathasan, S.; Limbergen, J. V.; Milgrom, R.; Proctor, D.; Regueiro, M.; Schumm, P. L.; Sharma, Y.; Stempak, J. M.; Targan, S. R.; Wang, M. H.

    2016-01-01

    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10−7, odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain. PMID:27503255

  19. Streptococcus thermophilus ST28 Ameliorates Colitis in Mice Partially by Suppression of Inflammatory Th17 Cells

    PubMed Central

    Ogita, Tasuku; Nakashima, Megumi; Morita, Hidetoshi; Saito, Yasuo; Suzuki, Takuya; Tanabe, Soichi

    2011-01-01

    The effects of Streptococcus thermophilus ST28 on cytokine production by murine splenocytes stimulated with transforming growth factor-β plus interleukin- (IL-) 6 were evaluated. The addition of ST28 significantly repressed IL-17 production compared to ATCC 19258 (type strain). ST28 also decreased the number of Th17 cells in the stimulated splenocytes. The anti-inflammatory effects of ST28 administration were evaluated in mice with colitis induced by dextran sodium sulphate (DSS). Oral treatment of mice with ST28 ameliorated the intestinal lesions by DSS. Upon DSS treatment, IL-17 production in lamina propria lymphocytes (LPLs) was induced, but ST28 significantly decreased its production. ST28 also decreased the percentage of Th17 cells in LPL from DSS-induced colitis. The present results imply that ST28 suppresses the Th17 response in inflamed intestines and would be useful in the treatment of Th17-mediated diseases, such as inflammatory bowel disease. PMID:22013382

  20. [Clinical trial of a novel spasmolytic, pramiverine, and its influence in colitis (author's transl].

    PubMed

    Toledo, G M

    1976-04-01

    In a double blind comparison of 4,4-diphenyl-N-isopropyl-cyclohexylamin-hydrochloride (pramiverine, Sistalgin) with placebo 51 patients with parasitis and bacterial colitis and enterocolitis as well as mixed forms of both were evaluated. The antiparasitic and antibacterial basic therapy was standardised in both groups. In the 27 patients treated with pramiverine the regression of the colitis syndrome starting within a few days was evaluated as excellent to good in 21 patients. In the placebo group similar improvements were observed only in 9 patients out of a total of 24. The good tolerance as compared to other spasmolytics should be equally emphasised as well as the slight inhibition of gastric secretion under prolonged therapy. PMID:782470

  1. [Dynamic renal scintigraphy in assessing kidney function in patients with nonspecific colitis].

    PubMed

    Topchiĭ, T V; Moskalenko, N I; Man'kovskaia, O L; Morozova, N L

    1990-11-01

    Research into the morphofunctional status of the kidneys was conducted in patients with nonspecific colitis-NC (nonspecific ulcerative colitis-NUC and Crohn's disease). Urodynamics and partial function of the kidneys were assessed in 74 NC patients (51 NUC patients and 23 patients with Crohn's disease) on the basis of the findings of two-nuclide dynamic renal scintigraphy with 131I-hippuran and 99mTc-pentatech. Despite the absence of clinical symptomatology of urinary tract lesions, marked dysfunction of the kidneys of various degree (depending on severity of disease, tactics of its treatment and a type of surgical intervention) was noted in NC patients. In most cases changes of renal function were without visible clinical manifestations and were frequently undetectable by routine laboratory tests. Therefore dynamic renal scintigraphy was found necessary for investigation on NC patients. PMID:2259285

  2. Preventive effects of cranberry products on experimental colitis induced by dextran sulphate sodium in mice.

    PubMed

    Xiao, Xiao; Kim, Jonggun; Sun, Quancai; Kim, Daeyoung; Park, Cheon-Seok; Lu, Tzong-Shi; Park, Yeonhwa

    2015-01-15

    With the prevalence of inflammatory bowel disease (IBD) and its associated risk for development of colorectal cancer, it is of great importance to prevent and treat IBD. However, due to the complexity of etiology and potentially serious adverse effects, treatment options for IBD are relatively limited. Thus, the purpose of this study was to identify a safe food-based approach for the prevention and treatment of IBD. In this study, we tested the effects of cranberry products on preventing dextran sulphate sodium-induced murine colitis. Our results suggest that both cranberry extract and dried cranberries-fed groups had a significantly reduced disease activity index, where dried cranberries were more effective in preventing colitis than cranberry extract. Shortening of colon length, colonic myeloperoxidase activity and production of pro-inflammatory cytokines were attenuated in animals fed dried cranberries compared to the controls. The current report suggests that cranberries can be applied to prevent and reduce the symptoms of IBD.

  3. Necrotic Colitis in Two Cats — A Description of the Lesions

    PubMed Central

    Wilkie, J. S. Nimmo

    1982-01-01

    The lesions in two cases of necrotic colitis in old cats are described. Both had gross lesions of a necrotic, hemorrhagic colitis without gross lesions in the small intestine. Histologically the lesions resembled those of feline panleukopenia virus infection, namely: necrosis and loss of crypt epithelium, dilation of crypts and lining of crypts by flattened epithelium, subsequent collapse of the lamina propria and hemorrhage from subepithelial capillaries. Both grossly and histologically these lesions were restricted to the colon without similar involvement of the small intestine. The histories and clinical signs, the virological and hematological studies suggest that feline panleukopenia virus was not the etiological agent in these cases. No other causal agent was identified. ImagesFigure 1. PMID:17422154

  4. Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis

    PubMed Central

    Pola, Suresh; Patel, Derek; Ramamoorthy, Sonia; McLemore, Elisabeth; Fahmy, Marianne; Rivera-Nieves, Jesus; Chang, John T; Evans, Elisabeth; Docherty, Michael; Talamini, Mark; Sandborn, William J

    2014-01-01

    Ulcerative colitis is a chronic inflammatory disease of the colon; as many as 25% of patients with this disease require hospitalization. The goals of hospitalization are to assess disease severity, exclude infection, administer rapidly acting and highly effective medication regimens, and determine response. During the hospitalization, patients should be given venous thromboembolism prophylaxis and monitored for development of toxic megacolon. Patients who do not respond to intravenous corticosteroids should be considered for rescue therapy with infliximab or cyclosporine. Patients who are refractory to medical therapies or who develop toxic megacolon should be evaluated promptly for colectomy. Patients who do respond to medical therapies should be discharged on an appropriate maintenance regimen when they meet discharge criteria. We review practical evidence-based management principles and propose a day-by-day algorithm for managing patients hospitalized for ulcerative colitis. PMID:22835577

  5. Prevention of colitis by controlled oral drug delivery of carbon monoxide.

    PubMed

    Steiger, Christoph; Uchiyama, Kazuhiko; Takagi, Tomohisa; Mizushima, Katsura; Higashimura, Yasuki; Gutmann, Marcus; Hermann, Cornelius; Botov, Svetlana; Schmalz, Hans-Günther; Naito, Yuji; Meinel, Lorenz

    2016-10-10

    Carbon monoxide (CO) is an endogenous signal transmitter involved in numerous physiological processes including the gastrointestinal (GI) homeostasis. CO has been recognized as potential new therapeutic agent for motility related and inflammatory disorders of the GI tract. A therapeutic use, however, is challenged by inappropriate drug delivery modes. Here we describe a micro scale Oral Carbon Monoxide Release System (M-OCORS) designed for localized and controlled exposure of the GI tract with in situ generated CO. M-OCORS allowed for controlled release profiles lasting for several minutes or up to almost one day. These in vitro release profiles translated into a large pharmacokinetic design space following oral administration in mice and measured as CO-hemoglobin (CO-Hb) formation. M-OCORS with a release profile featuring exposure of the intestine was profiled in two independently performed studies demonstrating preventive effects in chemically induced colitis. M-OCORS significantly reduced damage scores and prevented upregulation of colitis biomarkers.

  6. Isolated granulomatous hepatitis-A histopathological surprise mimicking cholangiocarcinoma in ulcerative colitis.

    PubMed

    Khandelwal, Ashish; Gorsi, Ujjwal; Marginean, E Celia; Papadatos, Demetri; George, Uttam

    2013-01-01

    A 63-yr-old woman, known case of ulcerative colitis, was diagnosed with sclerosing cholangitis 2 years back. She was admitted for investigation of abdominal discomfort, fatigue with elevated alkaline phosphatase and deranged liver function test. Imaging studies (computerised tomography and magnetic resonance imaging) demonstrated a normal biliary tree with focal hepatic lesion which was showing features of cholangiocarcinoma. Ultrasound guided biopsy of the lesion surprisingly revealed non caseating granulomata. Granulomatous hepatitis occurs in less than 1 percent of cases of inflammatory bowel disease. A clinical diagnosis of isolated granulomatous hepatitis was established as the lesion remained stable on follow up and no other cause for it was identified on further investigation. Although the differential diagnosis of focal hepatic lesion in patients with ulcerative colitis with sclerosing cholangitis is wide, granulomatous hepatitis presenting as focal mass lesion mimicking cholangiocarcinoma has never been described previously.

  7. Current approaches for optimizing the benefit of biologic therapy in ulcerative colitis

    PubMed Central

    Sofia, M. Anthony; Rubin, David T.

    2016-01-01

    As biologic-based medication options for ulcerative colitis expand, our understanding of their optimal use in clinical practice is advancing as well. The appropriate use of combination therapy with immunomodulators can reduce the immunogenicity of biologic agents and raise serum drug levels of the biologic. A treat-to-target strategy with objective assessments of disease activity clearly defines the goals of biologic drug treatment. Mucosal healing is an evolving treatment goal and is associated with long-term remission and reduced incidence of colectomy. Furthermore, regular reassessments and therapeutic drug monitoring can allow clinicians to make evidence-based changes in therapy. Biologic drug de-escalation or re-initiation are less well developed topics, but are emerging areas of study. We review the evidence underlying these advances and a modern approach to the use of biologic therapy in ulcerative colitis. PMID:27366223

  8. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.

    PubMed

    Rivas, Manuel A; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Sören; Kurki, Mitja I; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L E; Ananthakrishnan, Ashwin N; Luo, Yang; Heap, Graham A; Visschedijk, Marijn C; MacArthur, Daniel G; Neale, Benjamin M; Ahmad, Tariq; Anderson, Carl A; Brant, Steven R; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Palotie, Aarno; Saavalainen, Päivi; Kontula, Kimmo; Färkkilä, Martti; McGovern, Dermot P B; Franke, Andre; Stefansson, Kari; Rioux, John D; Xavier, Ramnik J; Daly, Mark J; Barrett, J; de Lane, K; Edwards, C; Hart, A; Hawkey, C; Jostins, L; Kennedy, N; Lamb, C; Lee, J; Lees, C; Mansfield, J; Mathew, C; Mowatt, C; Newman, B; Nimmo, E; Parkes, M; Pollard, M; Prescott, N; Randall, J; Rice, D; Satsangi, J; Simmons, A; Tremelling, M; Uhlig, H; Wilson, D; Abraham, C; Achkar, J P; Bitton, A; Boucher, G; Croitoru, K; Fleshner, P; Glas, J; Kugathasan, S; Limbergen, J V; Milgrom, R; Proctor, D; Regueiro, M; Schumm, P L; Sharma, Y; Stempak, J M; Targan, S R; Wang, M H

    2016-01-01

    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain. PMID:27503255

  9. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    PubMed

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased β-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased β-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

  10. Attenuation of Colitis by Lactobacillus casei BL23 Is Dependent on the Dairy Delivery Matrix.

    PubMed

    Lee, Bokyung; Yin, Xiaochen; Griffey, Stephen M; Marco, Maria L

    2015-09-01

    The role of the food delivery matrix in probiotic performance in the intestine is not well understood. Because probiotics are often provided to consumers in dairy products, we investigated the contributions of milk to the health-benefiting performance of Lactobacillus casei BL23 in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis. L. casei BL23 protected against the development of colitis when ingested in milk but not in a nutrient-free buffer simulating consumption as a nutritional supplement. Consumption of (acidified) milk alone also provided some protection against weight loss and intestinal inflammation but was not as effective as L. casei and milk in combination. In contrast, L. casei mutants deficient in DltD (lipoteichoic acid d-alanine transfer protein) or RecA (recombinase A) were unable to protect against DSS-induced colitis, even when consumed in the presence of milk. Mice fed either L. casei or milk contained reduced quantities of colonic proinflammatory cytokines, indicating that the L. casei DltD(-) and RecA(-) mutants as well as L. casei BL23 in nutrient-free buffer were effective at modulating immune responses. However, there was not a direct correlation between colitis and quantities of these cytokines at the time of sacrifice. Identification of the cecal microbiota by 16S rRNA gene sequencing showed that L. casei in milk enriched for Comamonadaceae and Bifidobacteriaceae; however, the consumption of neither L. casei nor milk resulted in the restoration of the microbiota to resemble that of healthy animals. These findings strongly indicate that probiotic strain efficacy can be influenced by the food/supplement delivery matrix.

  11. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.

    PubMed

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  12. Anti-inflammatory Efficiency of Ankaferd Blood Stopper in Experimental Distal Colitis Model

    PubMed Central

    Koçak, Erdem; Akbal, Erdem; Taş, Adnan; Köklü, Seyfettin; Karaca, Gökhan; Can, Murat; Kösem, Bahadır; Üstün, Hüseyin

    2013-01-01

    Background/Aim: Ankaferd blood stopper (ABS) is a herbal extract that enhances mucosal healing. In this study, we aimed to investigate the efficiency of ABS in the treatment of experimental distal colitis. Materials and Methods: Twenty one male albino rats were divided into three groups: Sham control (Group 1), colitis induced by acetic acid and treated with saline (Group 2), colitis induced by acetic acid and treated with ABS (Group 3). At end of the 7th day of induction, all the rats were lightly anesthetized with intramuscular ketamine (8 mg/kg) and thereafter laparotomy and total colectomy were performed. The distal colon segment was assessed macroscopically and microscopically. In addition malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) levels of the colonic tissue and changes in body weight were measured. Results: The MDA and NO levels of the colonic tissues and weight loss were significantly higher in Group 2 compared to Group 1 and Group 3. Microscopic and macroscopic damage scores were significantly higher in Group 2 and Group 3 than Group 1 (P: 0.001, P: 0.004, respectively). Although the microscopic and macroscopic damage scores in Group 3 were slightly lower than Group 2, the difference was not statistically significant. The SOD levels of the colonic tissues were not different between the three groups. Conclusion: Weight alterations and high-levels of the colonic tissue MDA and NO suggested that ABS might have anti-inflammatory effects on experimental distal colitis. However, this suggestion was not supported by histopathological findings. PMID:23680710

  13. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis

    PubMed Central

    Geboes, K; Riddell, R; Ost, A; Jensfelt, B; Persson, T; Lofberg, R

    2000-01-01

    BACKGROUND—Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials.
AIM—To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study.
METHODS—A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics.
RESULTS—Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration.
CONCLUSION—A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.


Keywords: ulcerative colitis; biopsy; inflammation; scoring system PMID:10940279

  14. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    PubMed

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis.

  15. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  16. Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis

    PubMed Central

    MacDonald, Marcia L.E.; Bissada, Nagat; Vallance, Bruce A.; Hayden, Michael R.

    2009-01-01

    Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model. PMID:19695343

  17. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    PubMed Central

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A.; Tsunoda, Ikuo

    2015-01-01

    Background: Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2(+/−) mice would influence the course of disease in a model of experimental colitis. Methods: Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2(+/−) mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. Results: We found that FoxC2 downregulation in FoxC2(+/−) mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. Conclusions: These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease. PMID:25822012

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

    PubMed Central

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

    2015-01-01

    Background and aims Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Methods Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. Results ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. Conclusions The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers. PMID:26605545

  19. Ulcerative colitis presenting as acute infectious gastroenteritis with a paralytic ileus

    PubMed Central

    Schoenmaker, Suzanne Gerdien; Tjon a Ten, Walther E

    2012-01-01

    A 15-year-old girl who presented with signs of acute infectious gastroenteritis, just as two members of her family is described. As the patient did not improve, a sigmoidoscopy was performed and the diagnosis of ulcerative colitis (UC) was made. Our hypothesis is that an infection triggered the development of UC. Her paralytic ileus was probably triggered by the increased nitric oxide produced in the macrophages and smooth muscles of the inflamed bowel. PMID:22605860

  20. Ischemic Colitis Has a Worse Prognosis When Isolated to the Right Side of the Colon

    PubMed Central

    Sotiriadis, John; Brandt, Lawrence J.; Behin, Daniel S.; Southern, William N.

    2009-01-01

    BACKGROUND In general, ischemic colitis has a very good prognosis, but there is concern that when ischemia affects the right side of the colon in an isolated fashion, the prognosis may not be so favorable. OBJECTIVE The aim of this study was to compare the clinical features and outcomes of ischemia isolated to the right side of the colon with those of ischemia involving other areas of the colon. METHODS A retrospective study was undertaken of patients with colon ischemia hospitalized at the Moses and Weiler Divisions of the Montefiore Medical Center during the interval 1998–2005. Patients were identified using computerized searches of ICD-9 codes for colon ischemia and were divided into two groups: those with isolated right colon ischemia (IRCI) and those with colon ischemia not involving the right colon in an isolated fashion (non-IRCI). Only patients with biopsy-proven ischemic colitis were entered into our study. RESULTS A total of 273 cases of biopsy-proven ischemic colitis were identified, of which 71 (26.0%) were isolated to the right side. Of these IRCI cases, 59.2% had an unfavorable outcome compared with 17.3% of cases of non-ICRI: 54.9% of IRCI patients required surgery compared with 10.9% of non-IRCI patients; mortality in patients with IRCI was 22.5% compared with 11.9% in patients with non-IRCI. CONCLUSIONS A total of 273 cases of biopsy-proven ischemic colitis were identified of which 71 (26.0%) involved only the right side. Patients with IRCI had a worse outcome than those with colon ischemia involving other colon regions, including a fivefold need for surgery and a twofold mortality. PMID:17561968

  1. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  2. Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis.

    PubMed

    Abdel-Aziz, Heba; Wadie, Walaa; Abdallah, Dalaal M; Lentzen, Georg; Khayyal, Mohamed T

    2013-05-15

    Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease (IBD). Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management. Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic/halotolerant bacteria, where it acts as osmoprotectant and effective biomembrane stabilizer, protecting the producing cells from extreme environmental stress. Since this natural compound was also shown to prevent inflammatory responses associated with IBD, its potential usefulness was studied in a model of colitis. Groups of rats were treated orally with different doses of ectoine (30-300 mg/kg) or sulfasalazine (reference drug) daily for 11 days. On day 8 colitis was induced by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid, when overt signs of lesions develop within the next 3 days. On day 12, blood was withdrawn from the retro-orbital plexus of the rats and the animals were sacrificed. The colon was excised and examined macroscopically and microscopically. Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates. Induction of colitis led to marked weight loss, significant histopathological changes of the colon, and variable changes in levels of myeloperoxidase, reduced glutathione, malondialdehyde, and all inflammatory markers tested. Treatment with ectoine ameliorated the inflammatory changes in TNBS-induced colitis. This effect was associated with reduction in the levels of TNF-α, IL-1β, ICAM-1, PGE2 and LTB4. The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD.

  3. Prevalence and Risk Factors for Therapy Escalation in Ulcerative Colitis in the Swiss IBD Cohort Study

    PubMed Central

    Safroneeva, Ekaterina; Vavricka, Stephan R.; Fournier, Nicolas; Straumann, Alex; Rogler, Gerhard

    2015-01-01

    Background: Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. Methods: Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. Results: Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. Conclusions: The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course. PMID:25806845

  4. Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation.

    PubMed

    Monk, Jennifer M; Lepp, Dion; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Pauls, K Peter; Tsao, Rong; Wood, Geoffrey A; Robinson, Lindsay E; Power, Krista A

    2016-02-01

    Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies.

  5. Attenuation of Colitis by Lactobacillus casei BL23 Is Dependent on the Dairy Delivery Matrix.

    PubMed

    Lee, Bokyung; Yin, Xiaochen; Griffey, Stephen M; Marco, Maria L

    2015-09-01

    The role of the food delivery matrix in probiotic performance in the intestine is not well understood. Because probiotics are often provided to consumers in dairy products, we investigated the contributions of milk to the health-benefiting performance of Lactobacillus casei BL23 in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis. L. casei BL23 protected against the development of colitis when ingested in milk but not in a nutrient-free buffer simulating consumption as a nutritional supplement. Consumption of (acidified) milk alone also provided some protection against weight loss and intestinal inflammation but was not as effective as L. casei and milk in combination. In contrast, L. casei mutants deficient in DltD (lipoteichoic acid d-alanine transfer protein) or RecA (recombinase A) were unable to protect against DSS-induced colitis, even when consumed in the presence of milk. Mice fed either L. casei or milk contained reduced quantities of colonic proinflammatory cytokines, indicating that the L. casei DltD(-) and RecA(-) mutants as well as L. casei BL23 in nutrient-free buffer were effective at modulating immune responses. However, there was not a direct correlation between colitis and quantities of these cytokines at the time of sacrifice. Identification of the cecal microbiota by 16S rRNA gene sequencing showed that L. casei in milk enriched for Comamonadaceae and Bifidobacteriaceae; however, the consumption of neither L. casei nor milk resulted in the restoration of the microbiota to resemble that of healthy animals. These findings strongly indicate that probiotic strain efficacy can be influenced by the food/supplement delivery matrix. PMID:26162873

  6. Attenuation of Colitis by Lactobacillus casei BL23 Is Dependent on the Dairy Delivery Matrix

    PubMed Central

    Lee, Bokyung; Yin, Xiaochen; Griffey, Stephen M.

    2015-01-01

    The role of the food delivery matrix in probiotic performance in the intestine is not well understood. Because probiotics are often provided to consumers in dairy products, we investigated the contributions of milk to the health-benefiting performance of Lactobacillus casei BL23 in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis. L. casei BL23 protected against the development of colitis when ingested in milk but not in a nutrient-free buffer simulating consumption as a nutritional supplement. Consumption of (acidified) milk alone also provided some protection against weight loss and intestinal inflammation but was not as effective as L. casei and milk in combination. In contrast, L. casei mutants deficient in DltD (lipoteichoic acid d-alanine transfer protein) or RecA (recombinase A) were unable to protect against DSS-induced colitis, even when consumed in the presence of milk. Mice fed either L. casei or milk contained reduced quantities of colonic proinflammatory cytokines, indicating that the L. casei DltD− and RecA− mutants as well as L. casei BL23 in nutrient-free buffer were effective at modulating immune responses. However, there was not a direct correlation between colitis and quantities of these cytokines at the time of sacrifice. Identification of the cecal microbiota by 16S rRNA gene sequencing showed that L. casei in milk enriched for Comamonadaceae and Bifidobacteriaceae; however, the consumption of neither L. casei nor milk resulted in the restoration of the microbiota to resemble that of healthy animals. These findings strongly indicate that probiotic strain efficacy can be influenced by the food/supplement delivery matrix. PMID:26162873

  7. Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model

    PubMed Central

    Zwintscher, Nathan P.; Shah, Puja M.; Salgar, Shashikumar K.; Newton, Christopher R.; Maykel, Justin A.; Samy, Ahmed; Jabir, Murad; Steele, Scott R.

    2016-01-01

    Introduction Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model. Methods A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon. Results DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P < 0.001). Discussion/Conclusion Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option. PMID:27144006

  8. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives.

    PubMed

    Tontini, Gian Eugenio; Vecchi, Maurizio; Pastorelli, Luca; Neurath, Markus F; Neumann, Helmut

    2015-01-01

    Distinction between Crohn's disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways. PMID:25574078

  9. Circulating antibodies to heat-shock protein 60 in Crohn's disease and ulcerative colitis.

    PubMed Central

    Stevens, T R; Winrow, V R; Blake, D R; Rampton, D S

    1992-01-01

    Heat-shock proteins (HSPs) are highly conserved immunogenic intracellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP-60 in the colonocytes of patients with ulcerative colitis. To study further the role of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member of the HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and, as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls (n = 20; median level of 89 ELISA units; range 24-292), serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; P < 0.05) and active ulcerative colitis (n = 16; 188; 58-373; P < 0.01) but not bacterial diarrhoea (n = 10; 106; 51-285). Increased IgA HSP-60 antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross-reactive anti-bacterial HSP antibodies. PMID:1424286

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

    PubMed

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

    2016-09-01

    Chronic inflammation in the intestine is a strong risk factor for colitis-associated colorectal cancer (CAC). Hydroxychloroquine (HCQ) is widely used as an anti-inflammatory drug in the treatment of immune-mediated inflammatory disorders and various tumors. However, little is known regarding the effects of HCQ on colitis-associated tumorigenesis. In this study, mice treated with HCQ showed a significant reduction in early-stage colitis following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration, as well as a remarkable inhibition of colonic tumorigenesis and tumor growth at late stages of CAC. Mechanistically, the therapeutic effects of HCQ were attributed to inhibition of inflammatory responses and production of mutagenic reactive oxygen species (ROS) in immune cells and subsequent promotion of apoptosis and cell cycle arrest in tumor cells. Furthermore, we found that HCQ inhibited the production of inflammatory cytokines and ROS in response to toll-like receptor 4 (TLR4) activation in macrophages. Our data presented herein may help guide the clinical use of HCQ as a prevention and treatment strategy for CAC. PMID:27288548

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

    PubMed Central

    Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

    2014-01-01

    The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

  12. Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling

    PubMed Central

    Ilott, Nicholas Edward; Bollrath, Julia; Danne, Camille; Schiering, Chris; Shale, Matthew; Adelmann, Krista; Krausgruber, Thomas; Heger, Andreas; Sims, David; Powrie, Fiona

    2016-01-01

    The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes. PMID:27003245

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

    PubMed

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

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

  14. Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis.

    PubMed Central

    Marshall, J K; Irvine, E J

    1997-01-01

    BACKGROUND: Clear strategies to optimise the use of corticosteroids in ulcerative colitis are lacking. AIM: A meta-analysis was undertaken to examine critically the role of rectal corticosteroids in the management of active distal ulcerative colitis. METHODS: All reported randomised controlled trials were retrieved by searching the Medline and EMBASE databases and the bibliographies of relevant studies. Trials which met inclusion criteria were assessed for scientific rigour. Data were extracted by two independent observers according to predetermined criteria. RESULTS: Of 83 trials retrieved, 33 met inclusion criteria. Pooled odds ratios (POR) showed conventional rectal corticosteroids and rectal budesonide to be clearly superior to placebo. In seven trials, rectal 5-aminosalicylic acid (5-ASA) was significantly better than conventional rectal corticosteroids for inducing remission of symptoms, endoscopy, and histology with POR of 2.42 (95% confidence interval (CI) 1.72-3.41), 1.89 (95% CI 1.29-2.76), and 2.03 (95% CI 1.28-3.20), respectively. Rectal budesonide was of comparable efficacy to conventional corticosteroids but produced less endogenous cortisol suppression. Side effects, although inconsistently reported, were generally minor. A cost comparison of rectal preparations showed 5-ASA to be less expensive than corticosteroids. CONCLUSIONS: Rectal 5-ASA is superior to rectal corticosteroids in the management of distal ulcerative colitis. PMID:9245932

  15. Effect of Nanometric Lactobacillus plantarum in Kimchi on Dextran Sulfate Sodium-Induced Colitis in Mice.

    PubMed

    Lee, Hyun Ah; Bong, Yeon-Ju; Kim, Hyunung; Jeong, Ji-Kang; Kim, Hee-Young; Lee, Kwang-Won; Park, Kun-Young

    2015-10-01

    Nanometric Lactobacillus plantarum (nLp) is a processed form of Lab. plantarum derived from kimchi and is 0.5-1.0 μm in size. This study was undertaken to determine the effect of nLp and kimchi plus nLp (K-nLp) on a dextran sulfate sodium (DSS)-induced mouse model of colitis. Animals fed nLp or K-nLp had longer colons, but lower colon weights per unit length than DSS controls. In addition, nLp- or K-nLp-fed animals showed lower levels of proinflammatory cytokines and inflammatory genes in serum and in colon tissues, lower populations of total bacteria, but higher populations of lactic acid bacteria in feces, and lower activities of fecal β-glucosidase and β-glucuronidase. Furthermore, these suppressive activities of nLp on colitis were equivalent to or higher than those of naive Lab. plantarum. Consequently, nLp was found to exhibit anticolitic effects, and the addition of nLp to kimchi was found to enhance the protective activity of kimchi against DSS-induced colitis. These results suggest that nLp might be an effective substitute for live probiotics and be useful as a functional ingredient with the anticolitic activity by the probiotic and food processing industries.

  16. Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

    PubMed

    Gautam, M K; Ghatule, R R; Singh, A; Purohit, V; Gangwar, M; Kumar, Mohan; Goel, R K

    2013-02-01

    Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine. PMID:23923609

  17. Biological and Histological Parameters as Predictors of Relapse in Ulcerative Colitis: A Prospective Study

    PubMed Central

    Azad, Sheenam; Sood, Neena; Sood, Ajit

    2011-01-01

    Background/Aim: Ulcerative colitis is a chronic inflammatory disease of unknown etiology characterized by periods of remission and relapses. This study has been carried out in a group of North Indian patients, where the disease has shown an increasing prevalence and frequent relapses. Hence, there is a need to predict relapse for better management and to reduce morbidity. To assess the importance of biological and histological parameters in predicting relapse when the disease is in quiescent phase. Materials and Methods: A prospective study of twenty-six patients with quiescent ulcerative colitis was carried out in Dayanand Medical College and Hospital, Punjab. Only patients with clinical and endoscopic remission at the time of screening visit were included. Hemoglobin, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and serum Interleukin-6 (IL-6) levels were measured. The baseline colonoscopic mucosal biopsies were retrieved and studied. Follow-up was conducted for one year at monthly interval or earlier if relapse occurred. Results: Fifteen out of twenty-six patients (57.69%) had evidence of clinical relapse during the follow-up. Hemoglobin, ESR, CRP and IL-6 levels were not found to be significant predictors of relapse. Increased number of eosinophils and neutrophils in the lamina propria were observed to be associated with significantly higher relapse rate. Conclusion: A higher risk of relapse in patients with quiescent colitis can be predicted by the presence of increased number of eosinophils and neutrophils in the lamina propria. PMID:21546723

  18. A reappraisal of the ileo-rectal anastomosis in ulcerative colitis.

    PubMed

    Myrelid, Pär; Øresland, Tom

    2015-06-01

    Colectomy is still frequently required in the care of ulcerative colitis. The most common indications are either non-responding colitis in the emergency setting, chronic active disease, steroid-dependent disease or neoplastic change like dysplasia or cancer. The use of the ileal pouch anal anastomosis has internationally been the gold standard, substituting the rectum with a pouch. Recently the use of the ileorectal anastomosis has increased in frequency as reconstructive method after subtotal colectomy. Data from centres using ileorectal anastomosis have shown the method to be safe, with functionality and risk of failure comparable to the ileal pouch anal anastomosis. The methods have different advantages as well as disadvantages, depending on a number of patient factors and where in life the patient is at time of reconstruction. The ileorectal anastomosis could, together with the Kock continent ileostomy, in selected cases be a complement to the ileal pouch anal anastomosis in ulcerative colitis and should be discussed with the patient before deciding on reconstructive method.

  19. Vinegar Treatment Prevents the Development of Murine Experimental Colitis via Inhibition of Inflammation and Apoptosis.

    PubMed

    Shen, Fengge; Feng, Jiaxuan; Wang, Xinhui; Qi, Zhimin; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Wang, Chao; Liu, Mingyuan; Liu, Bo; Yu, Lu

    2016-02-10

    This study investigated the preventive effects of vinegar and acetic acid (the active component of vinegar) on ulcerative colitis (UC) in mice. Vinegar (5% v/v) or acetic acid (0.3% w/v) treatment significantly reduced the disease activity index and histopathological scores, attenuated body weight loss, and shortened the colon length in a murine experimental colitis model induced by dextran sulfate sodium (DSS). Further mechanistic analysis showed that vinegar inhibited inflammation through suppressing Th1 and Th17 responses, the NLRP3 inflammasome, and MAPK signaling activation. Vinegar also inhibited endoplasmic reticulum (ER) stress-mediated apoptosis in the colitis mouse model. Surprisingly, pretreatment with vinegar for 28 days before DSS induction increased levels of the commensal lactic acid-producing or acetic acid-producing bacteria, including Lactobacillus, Bifidobacteria, and Enterococcus faecalis, whereas decreased Escherichia coli levels were found in the feces of mice. These results suggest that vinegar supplementation might provide a new dietary strategy for the prevention of UC.

  20. Therapeutic efficacy and mechanism of Zhenrenyangzang decoction in rats with experimental ulcerative colitis

    PubMed Central

    Wang, Hui; Li, Shu-Hua; Zhang, Yan; Guan, Jie; Wu, Yan-Min; Wang, Qi; Luo, Xiao-Qing

    2015-01-01

    Zhenrenyangzang Decoction (ZD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as chronic gastritis. However, there is less study on its application in ulcerative colitis (UC) and the effects are not yet clearly defined. To explore the effectiveness of ZD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats, ZD was administered orally for 8 days at a dosage of 2, 4 or 8 g/kg/day. Following drug administration, the disease activity index (DAI) and tissue damage scores were recorded. In addition, mRNA and protein expression of nuclear factor kappa B (NF-κB), p38 mitogen activated protein kinase (p38MAPK) and Toll-like receptor 2 (TLR2) in colon tissues were examined by real time PCR and western blotting assay. As compared with the UC model group, ZD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the mRNA or protein expression of NF-κB and p38MAPK, as well as activating the production of TLR2 in colon tissues. And ZD significantly reduced the DAI and tissue damage scores. The therapeutic effect of ZD was found to be comparable to that of SASP. Our results suggested that ZD could improve colonic mucosa impairment and possesses favorable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application. PMID:26629011

  1. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis. PMID:26620574

  2. Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats

    PubMed Central

    Nosalova, Viera; Navarova, Jana

    2013-01-01

    Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested, only CNC (2 × 50 mg/kg) effectively depressed inflammatory damage of the colon. The mechanism of this beneficial effect remains to be elucidated. PMID:24170973

  3. Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut

    PubMed Central

    Wang, Tingting; Pan, Deng; Zhou, Zhicheng; You, Yun; Jiang, Changying; Zhao, Xueqiang; Lin, Xin

    2016-01-01

    Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis. Here we found that mice deficient in Dectin-3 (Clec4d-/-), a C-type lectin receptor that senses fungal infection, were more susceptible to dextran sodium sulfate (DSS)-induced colitis compared with wild-type mice. The specific fungal burden of Candida (C.) tropicalis was markedly increased in the gut after DSS treatment in Clec4d-/- mice, and supplementation with C. tropicalis aggravated colitis only in Clec4d-/- mice, but not in wild-type controls. Mechanistically, Dectin-3 deficiency impairs phagocytic and fungicidal abilities of macrophages, and C. tropicalis-induced NF-κB activation and cytokine production. The conditioned media derived from Dectin-3-deficient macrophages were defective in promoting tissue repairing in colonic epithelial cells. Finally, anti-fungal therapy was effective in treating colitis in Clec4d-/- mice. These studies identified the role of Dectin-3 and its functional interaction with commensal fungi in intestinal immune system and regulation of colonic homeostasis. PMID:27280399

  4. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection

    PubMed Central

    Hao, Xing Pei; Lucero, Carissa M.; Turkbey, Baris; Bernardo, Marcelino L.; Morcock, David R.; Deleage, Claire; Trubey, Charles M.; Smedley, Jeremy; Klatt, Nichole R.; Giavedoni, Luis D.; Kristoff, Jan; Xu, Amy; Del Prete, Gregory Q.; Keele, Brandon F.; Rao, Srinivas S.; Alvord, W. Gregory; Choyke, Peter L.; Lifson, Jeffrey D.; Brenchley, Jason M.; Apetrei, Cristian; Pandrea, Ivona; Estes, Jacob D.

    2015-01-01

    Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis. PMID:26282376

  5. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice.

    PubMed

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio; Rodriguez-Monroy, Marco Aurelio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as "cuachalalate." Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  6. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    PubMed Central

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis. PMID:27635116

  7. Sequential release of cytokines, lipid mediators and nitric oxide in experimental colitis

    PubMed Central

    Keuskamp, Z. J.; Wilson, J. H. P.; Zijlstra, F. J.

    1995-01-01

    The object of this study was to establish whether different pro- and anti-inflammatory mediators were formed in colonic tissue from experimental colitis depending on the course of the disease. Concentrations of mediators of inflammation were examined in colonic tissue in dextran induced colitis in mice. Initial inflammation was produced by 5 days treatment of 10% dextran sodium sulfate (DSS) in drinking water, followed by a further 9 day period of 2% DSS in an attempt to produce a milder chronic inflammation. The degree of inflammation was scored by a standardized macroscopic and histological examination. Initially, a 60% maximum inflammation score was observed at day 4. At this time inflammation was associated with the release of interleukin-lβ (IL-1β) and tumour necrosis factor-α (TNFα), whereas both prostaglandins 6kPGF1α and PGE2 and nitric oxide (NO) markedly decreased. Then a 25% inflammation score was reached which coincided with an increased production of platelet-activating factor (PAF). No significant changes were observed in leukotriene B4 and C4 formation. In conclusion, pro-inflammatory cytokines IL-1β and TNFα are considered to be primary mediators, whereas PAF, eicosanoids and NO may reflect secondary mediators in experimental colitis. PMID:18475637

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

    de Souza, Patrícia Reis; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

  10. Protective Effect of Amphipterygium adstringens Extract on Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

    PubMed Central

    Rodriguez-Canales, Mario; Jimenez-Rivas, Ruben; Canales-Martinez, Maria Margarita; Garcia-Lopez, Ana Judith; Rivera-Yañez, Nelly; Nieto-Yañez, Oscar; Ledesma-Soto, Yadira; Sanchez-Torres, Luvia Enid; Rodriguez-Sosa, Miriam; Terrazas, Luis Ignacio

    2016-01-01

    Amphipterygium adstringens is an endemic species in Mexico commonly known as “cuachalalate.” Healers to treat gastritis, gastric ulcers, and gastrointestinal cancer have traditionally used the bark. We investigated the effects of alcoholic extract of A. adstringens (AaEE) in DSS-induced colitis in mice. The protective effect of AaEE was determined at 200 mg/kg by oral gavage for 10 days. We determine the effect of AaEE on clinical features (disease activity index), antioxidants, anti-inflammatory, and immunomodulatory activities in relation to the activity of SOD, CAT, and GPx, levels of proinflammatory cytokines, and changes both macroscopic and microscopic of the colonic mucosa. AaEE significantly reduced the inflammation of colon and significantly increased SOD and GPx activities. AaEE also significantly decreased TNF-α, IFN-γ, and IL-1β cytokine levels compared to DSS-treated mice and reduced both infiltration of inflammatory cells and the mucosal damage in colon. The results suggested the protective potential of AaEE in DSS-induced colitis and this might be attributed to its phytochemicals compounds that have been found to induce a wide spectrum of activities such as reduction in oxidative stress, suppression of inflammation, modulating numerous signal transduction pathways, and induction of apoptosis. The findings of this study suggest that AaEE has substantial potential for the treatment of inflammatory colitis.

  11. Colon perforation with peritonitis in an acquired immunodeficiency syndrome patient due to cytomegalovirus and amoebic colitis.

    PubMed

    Tsai, Hung-Chin; Lee, Susan Shin-Jung; Wann, Shue-Ren; Chen, Yao-Shen; Chen, Eng-Rin; Yen, Chuan-Min; Liu, Yung-Ching

    2005-11-01

    Invasive amoebiasis is rarely seen in human immunodeficiency virus (HIV)-infected individuals, even in endemic areas. By contrast, cytomegalovirus (CMV) disease is recognized as a major clinical problem in acquired immunodeficiency syndrome patients. A 34-year-old HIV-infected man with amoeba colitis, disseminated Mycobacterium avian complex and CMV infection with cecum perforation, presented with the initial symptoms of fever, shortness of breath and painful sensation when swallowing. He was treated with fluconazole, trimethoprim-sulfamethoxazole and hydrocortisone under the impression of esophageal candidiasis and Pneumocystis jiroveci pneumonia. However, diarrhea and abdominal pain developed on day 6 of hospitalization. Invasive amoebiasis and CMV colitis was diagnosed after examination of colon pathological specimens. Emergent laparotomy was performed. Right hemicolectomy with double barrel ileostomy and colostomy was done due to perforation of the cecum. Iodoquinol was given, followed by metronidazole 14 days afterwards. He underwent closure of double barrel ileostomy and colostomy 5 months later. This case illustrates the diagnostic challenge of caring for acquired immunodeficiency syndrome persons with multiple illnesses and medication use. CMV infection, amoebic colitis and possibly corticosteroid may have played a role in colon perforation in our patient.

  12. Royal Jelly and Its Dual Role in TNBS Colitis in Mice

    PubMed Central

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

    2015-01-01

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

  13. [Amebic colitis and liver abscess complicated by high serum procalcitonin in acute myeloid leukemia].

    PubMed

    Oku, Eijiro; Nomura, Kei; Nakamura, Takayuki; Morishige, Satoshi; Seki, Ritsuko; Imamura, Rie; Hashiguchi, Michitoshi; Osaki, Kouichi; Mizuno, Shinichi; Nagafuji, Koji; Okamura, Takashi

    2012-11-01

    We present a case of amebic colitis and liver abscess complicated by acute myeloid leukemia (AML) with high serum procalcitonin (PCT). A 61-year-old Japanese man seen at our hospital for severe diarrhea and high fever was found to have multiple ulcers in the transverse and sigmoid colon and rectum by colonoscopy and biopsies were conducted. Immature leukocytes with mild anemia and thrombocytopenia were seen in peripheral blood, necessitating bone marrow aspiration and biopsy that yielded a diagnosis of AML (FAB M4Eo). Serum C-reactive protein and PCT were extremely elevated. Blood cultures for bacteria and fungi were negative. Multiple low-density areas in the liver were found in abdominal computed tomography. Histological colon biopsy findings revealed amebic colitis, strongly suggesting amebic liver abscess. Metronidazole treatment was initiated for amebiasis and subsequent standard chemotherapy for AML was followed after fever was lowered. Hematological and cytogenetic CR was maintained with good clinical condition. Few case reports have been published in Japan to date on amebic colitis and liver abscess complicated by AML and no reports have been made on PCT elevation caused by amebiasis. In conclusion, differential diagnosis of amebiasis is necessary in addition to that of bacterial or fungal infection in serum PCT elevation. PMID:23367854

  14. Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis

    PubMed Central

    Ro, Seung-Hyun; Xue, Xiang; Ramakrishnan, Sadeesh K; Cho, Chun-Seok; Namkoong, Sim; Jang, Insook; Semple, Ian A; Ho, Allison; Park, Hwan-Woo; Shah, Yatrik M; Lee, Jun Hee

    2016-01-01

    The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation and colon cancer growth. Sestrins are stress-inducible proteins, which suppress both mTORC1 and ER stress; however, the role of Sestrins in colon physiology and tumorigenesis has been elusive due to the lack of studies in human tissues or in appropriate animal models. In this study, we show that human SESN2 expression is elevated in the colon of ulcerative colitis patients but is lost upon p53 inactivation during colon carcinogenesis. In mouse colon, Sestrin2 was critical for limiting ER stress and promoting the recovery of epithelial cells after inflammatory injury. During colitis-promoted tumorigenesis, Sestrin2 was shown to be an important mediator of p53’s control over mTORC1 signaling and tumor cell growth. These results highlight Sestrin2 as a novel tumor suppressor, whose downregulation can accelerate both colitis and colon carcinogenesis. DOI: http://dx.doi.org/10.7554/eLife.12204.001 PMID:26913956

  15. Interleukin 2 and interferon-gamma augment anticolon antibody dependent cellular cytotoxicity in ulcerative colitis.

    PubMed Central

    Hibi, T; Ohara, M; Watanabe, M; Kanai, T; Takaishi, H; Hayashi, A; Hosoda, Y; Ogata, H; Iwao, Y; Aiso, S

    1993-01-01

    In vitro effects of cytokines and therapeutic drugs on antibody dependent cellular cytotoxicity (ADCC) mediated by anticolon antibody were investigated in serum samples from patients with ulcerative colitis. A 51Cr release assay was used to examine ADCC activity with the colon cancer cell line, colo 205, as the target and peripheral blood mononuclear cells as the effector. High ADCC activity was shown in 13 of 32 (41%) patients with ulcerative colitis. This ADCC activity was inhibited by protein A treatment of the serum samples. Interleukin 2 (IL2) activated effector cells could enhance ADCC activity, but interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) had no effect on the cytotoxic activity of effector cells. Treatment of target cells with IFN-gamma increased the vulnerability of these cells to ADCC with a large increase of intercellular adhesion molecule-1 (ICAM-1) expression on their surface. Monoclonal antibodies to ICAM-1 inhibited this IFN-gamma enhanced ADCC activity. Interestingly, prednisolone (PSL) reduced ADCC activity, but sulphasalazine (SASP) or 5-aminosalicylic acid (5-ASA) did not. These results suggest that IL2 and IFN-gamma could enhance colonic epithelial cell injury mediated by the ADCC mechanism in ulcerative colitis and that ADCC enhanced by cytokines is restored by PSL treatment. PMID:8100205

  16. Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling.

    PubMed

    Ilott, Nicholas Edward; Bollrath, Julia; Danne, Camille; Schiering, Chris; Shale, Matthew; Adelmann, Krista; Krausgruber, Thomas; Heger, Andreas; Sims, David; Powrie, Fiona

    2016-10-01

    The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes. PMID:27003245

  17. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

    PubMed Central

    Pandurangan, Ashok Kumar; Mohebali, Nooshin; Norhaizan, Mohd Esa; Looi, Chung Yeng

    2015-01-01

    Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA. PMID:26251571

  18. Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives

    PubMed Central

    Tontini, Gian Eugenio; Vecchi, Maurizio; Pastorelli, Luca; Neurath, Markus F; Neumann, Helmut

    2015-01-01

    Distinction between Crohn’s disease of the colon-rectum and ulcerative colitis or inflammatory