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Sample records for colitis collagenous colitis

  1. Collagenous Colitis and Spondylarthropathy

    PubMed Central

    Ben Abdelghani, Kaouther; Sahli, Hana; Souabni, Leila; Chekili, Selma; Belhadj, Salwa; Kassab, Selma; Laatar, Ahmed; Zakraoui, Leith

    2012-01-01

    Collagenous colitis is a recent cause of chronic diarrhea. Cooccurrence with spondylarthropathy is rare. We describe two cases: one man and one woman of 33 and 20 years old were suffering from spondylarthropathy. They then developed collagenous colitis, 4 and 14 years after the onset of spondylarthropathy. The diagnosis was based on histological features. A sicca syndrome and vitiligo were observed with the female case. The presence of colitis leads to therapeutic problems. This association suggests a systemic kind of rheumatic disease of collagenous colitis. PMID:22701491

  2. 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.

  3. Pseudomembranous collagenous colitis with superimposed drug damage.

    PubMed

    Villanacci, Vincenzo; Cristina, Silvia; Muscarà, Maurizio; Saettone, Silvia; Broglia, Laura; Antonelli, Elisabetta; Salemme, Marianna; Occhipinti, Pietro; Bassotti, Gabrio

    2013-11-01

    Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis. PMID:24080283

  4. Long-term natural history and complications of collagenous colitis

    PubMed Central

    Freeman, Hugh J

    2012-01-01

    Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal ‘dissection’, colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids). Finally, lymphoproliferative disease has been reported. PMID:22993735

  5. 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

  6. Optimal management of collagenous colitis: a review.

    PubMed

    O'Toole, Aoibhlinn

    2016-01-01

    Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC's natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications. PMID:26929656

  7. 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

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

    PubMed

    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

  9. 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

  10. 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

  11. [Microscopic colitis: update 2014].

    PubMed

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

    2014-09-01

    Microscopic colitis, which includes lymphocytic colitis and collagenous colitis, represents a frequent cause of chronic watery diarrhea especially in the elderly population. Several medications, such as nonsteroidal antiinflammatory drugs, proton pump inhibitors or antidepressants, as well as cigarette smoking have been recognized as risk factors for microscopic colitis. The diagnosis of microscopic colitis is based on a macroscopically normal ileo-colonoscopy and several biopsies from the entire colon, which demonstrate the pathognomonic histopathologic findings. Therapy is mainly based on the use of budesonide. Other medications, such as mesalazine, cholestyramine and bismuth, have been evaluated as well but the evidence is less solid. PMID:25276996

  12. Microscopic colitis.

    PubMed

    Pardi, Darrell S

    2014-02-01

    Microscopic colitis is a frequent cause of chronic watery diarrhea, especially in older persons. Common associated symptoms include abdominal pain, arthralgias, and weight loss. The incidence of microscopic colitis had been increasing, although more recent studies have shown a stabilization of incidence rates. The diagnosis is based on characteristic histologic findings in a patient with diarrhea. Microscopic colitis can occur at any age, including in children, but it is primarily seen in the elderly. Several treatment options exist to treat the symptoms of microscopic colitis, although only budesonide has been well studied in randomized clinical trials. PMID:24267602

  13. 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

  14. Ulcerative Colitis

    MedlinePlus

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

  15. Ulcerative colitis

    MedlinePlus

    ... of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology . 2015;148(5):1035-58. PMID: 25747596 www.ncbi.nlm.nih.gov/pubmed/25747596 . Burger D, Travis S. Conventional medical management of inflammatory bowel ...

  16. [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

  17. 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

  18. Anti-PD1-induced collagenous colitis in a melanoma patient.

    PubMed

    Baroudjian, Barouyr; Lourenco, Nelson; Pagès, Cécile; Chami, Ichrak; Maillet, Marianne; Bertheau, Philippe; Bagot, Martine; Gornet, Jean-Marc; Lebbé, Céleste; Allez, Matthieu

    2016-06-01

    Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first-line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 µm thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab. PMID:26990271

  19. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-21

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

  2. Eosinophilic colitis.

    PubMed

    Dionísio de Sousa, Isabel José; Bonito, Nuno; Pais, Ana; Gervásio, Helena

    2016-01-01

    A 57-year-old man, diagnosed with colon cancer stage III in July/2010, underwent surgery and received adjuvant chemotherapy with FOLFOX 4 (5-fluorouracil; calcium folinate and oxaliplatin), which ended in March/2011 after 12-cycles. It was then decided to maintain periodical surveillance. About 1 year later, the patient developed several episodes of diarrhoea, mainly during the night, and presented persistent peripheral eosinophilia in the blood count (range 585-1300 eosinophils/µL). Colonoscopy was performed, with the histological result showing eosinophilic infiltration of the colon, compatible with eosinophilic colitis. The patient was treated with a short course of budesonide, achieving resolution of symptoms, and has remained asymptomatic. PMID:26957036

  3. [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

  4. Ulcerative Colitis: An Overview

    PubMed Central

    Archambault, Andre

    1990-01-01

    Idiopathic ulcerative colitis primarily affects young adults. Colonic symptoms are the most annoying. In severe colitis, systemic and extraintestinal inflammatory manifestations can be disabling. Proximal extension of colitis is demonstrated by double-contrast barium enema and total colonoscopy. Bacterial and parasitic colitis must be excluded by appropriate microbiological studies. Colonoscopy is recommended to screen for high-grade dysplasia or neoplasia in cases of chronic diffuse colitis (after seven years). Severe colitis can benefit from hospitalization, parenteral nutritional support, and high doses of corticosteroids that are progressively tapered. Mild or moderate cases or severe cases in remission respond well to rest, low-irritant diets, mild symptomatic medication, oral sulfasalazine, or more recent 5-acetylsalicylic derivatives. Long-term maintenance with reduced dosages will control more than 80% of cases. PMID:21234051

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

    PubMed

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

    2016-08-25

    Ulcerative colitis, particularly the chronic persistent form is characterized by the presence of active inflammation and extensive areas of ulceration in the colonic mucosa. The existing treatment protocol aims at only reducing intestinal inflammation, rather than targeting mucosal ulceration. In this study, type I collagen and its daughter peptides called collagen hydrolysate, highly popular reconstructive materials for tissue engineering applications, are hypothesized as healing matrices to target the recuperation of internal mucosal ulceration. The clinical assessments on day 10 of dextran sodium sulfate induced colitis in mice model revealed that both the collagen (1.56±0.29) and collagen hydrolysate treatments (1.33±0.33) showed a significant reduction in the rectal bleeding compared to the reference mesalamine treatment (2.50±0.33) and untreated negative control (2.40±0.40). VEGF, a potent angiogenic growth factor, over expressed during UC was down-regulated by collagen hydrolysate (1.06±0.25) and collagen (1.76±0.45) to a greater extent than by mesalamine (2.59±0.51) and untreated control (4.17±0.15). The down-regulation of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 also follows the same pattern. Histological observations were in accordance with the clinical indicators. Both collagen and collagen hydrolysate treatments showed significant reduction in mucosal damage score and facilitated faster regeneration of damaged mucosa. PMID:27185300

  6. Lubiprostone induced ischemic colitis.

    PubMed

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

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

  7. Types of Ulcerative Colitis

    MedlinePlus

    ... Colitis Types of Medications What’s available to treat IBD and what you should know about these medications. ... Info Specialist Teen Website Understand How To Manage IBD Learn about IBD treatments, diet, complications, and quality ...

  8. Acyclovir-induced colitis.

    PubMed

    Wardle, T D; Finnerty, J P; Swale, V; Beer, T

    1997-04-01

    Three patients developed acute colitis, either de novo, or as an exacerbation of pre-existing colitis, following the use of oral acyclovir, prescribed for Herpes zoster or Herpes simplex infection. Rechallenge with oral acyclovir was performed in one patient, and resulted in a recurrence of colitic symptoms. It is speculated that acyclovir can have a direct irritant effect on large bowel mucosa. PMID:9146784

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

    PubMed Central

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

    2011-01-01

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

  10. 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

  11. 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 ...

  12. Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis

    MedlinePlus

    ... images. A patient does not need anesthesia. Health care providers use imaging tests to show physical abnormalities and to diagnose certain ... prep instructions to follow at home before the test. The health care provider will also explain what the patient can ...

  13. 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

  14. 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

  15. Fulminant amebic colitis.

    PubMed

    Aristizábal, H; Acevedo, J; Botero, M

    1991-01-01

    Amebiasis is the acute and chronic disease produced by Entamoeba histolytica, an entity which occurs in endemic fashion in many of the tropical and subtropical areas of the world, capable of affecting diverse organs of the body, especially the colon. Amebiasis has different clinical forms of presentation, varying from the asymptomatic carrier state to severe, although not frequent, fulminant or necrotizing colitis, characteristically associated with high morbidity and mortality. We hereby report a series of 50 adult patients with fulminating amebic colitis managed at our institution between January, 1971 and July, 1989, with a global mortality of 60%. Early diagnosis, treatment with effective antiamebic agents--specifically metronidazole--and opportune aggressive surgical intervention have resulted in better survival rates. We had no survivors prior to 1970; our current survival rate is still a dismal 40%, indicating the very severe nature of the disease. PMID:2031357

  16. 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

  17. Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?

    PubMed Central

    Lim, A; Langmead, F; Feakins, R; Rampton, D

    1999-01-01

    The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine. 

 Keywords: ulcerative colitis, diversion colitis PMID:9895391

  18. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

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

    2013-01-01

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

  19. Pyoderma gangrenosum in ulcerative colitis.

    PubMed

    Misra, S P; Singh, S K; Chari, S T; Sarin, S K; Anand, B S

    1991-07-01

    We present a patient with pyoderma gangrenosum, a rare complication of ulcerative colitis. The patient's disease was limited to the distal colon, was clinically mild and responded quickly to treatment, and yet it was associated with pyoderma gangrenosum and arthritis, complications generally associated with more severe and extensive ulcerative colitis. PMID:1839305

  20. [Pseudomembranous colitis caused by antibiotics].

    PubMed

    Meyer, B; Geering, P

    1978-11-11

    A case of antibiotic-induced pseudomembranous colitis is presented. Following resection of a carcinoma of the colon, an 81-year old man was treated with clindamycin for 9 days and with epicillin for another 9 days. One week after discontinuation of antibiotics the patient developed progressively severe diarrhea. Death from central pulmonary embolism ensued 10 days after the onset of diarrhea. Autopsy revealed severe pseudomembranous colitis of the entire large intestine. Pseudomembranous colitis is often observed as a complication after the administration of different antibiotics. The Anglo-American literature contains several recent reports of clindamycin-induced pseudomembranous colitis. The etiopathology of this drug-induced disease is still unclear. A possible interpretation is an antibiotic-induced change in the intestinal flora. Recent observations suggest that toxin-producing clostridia are responsible for the pseudomembranous colitis. PMID:568308

  1. Tofacitinib in ulcerative colitis.

    PubMed

    Archer, Thomas P; Moran, Gordon W; Ghosh, Subrata

    2016-05-01

    Cytokines orchestrate immune and inflammatory responses involved in the pathogenesis of ulcerative colitis (UC). Protein kinases are essential for signal transduction in eukaryotic cells. Janus kinases (JAKs) are a family of protein tyrosine kinases that play a pivotal role in cytokine receptor signaling. Indeed, a major subgroup of cytokines use Type I and II cytokine receptors which signal via the activation of JAKs. Tofacitinib is an oral JAK inhibitor that has been studied in autoimmune pathologies, including UC and rheumatoid arthritis with good overall efficacy and acceptable safety profile. This literature review was performed with the goal of summarizing the knowledge on JAK inhibitors in UC treatment. PMID:27140405

  2. 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 ...

  3. 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

  4. 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

  5. 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

  6. Fucoidan Extracts Ameliorate Acute Colitis

    PubMed Central

    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

  7. Colitis possibly induced by quetiapine.

    PubMed

    de Beaurepaire, Renaud; Trinh, Isabelle; Guirao, Sophie; Taieb, Muriel

    2015-01-01

    A 39-year-old man with bipolar disorder was hospitalised for depression. He was started on quetiapine (titrated up to 300 mg), lactulose (a laxative) and tropatepine (an anticholinergic). Valpromide (a mood stabiliser) and prazepam were later added and rapidly withdrawn. Seven days after quetiapine initiation, the patient reported abdominal pain and constipation; 2 days later, CT revealed an important distention of the colon including the caecum and a pre-perforation. A subtotal colectomy was performed and histology confirmed necrotising ischaemic colitis. The patient survived. This is the first case reported so far of ischaemic colitis related to quetiapine, in the absence of other antipsychotics simultaneously prescribed. Tropatepine likely acted as a cofactor to determine colitis. Clinicians need to be aware of the potential danger of the co-prescription of quetiapine with tropatepine (and possibly other anticholinergics). PMID:25721830

  8. Colonic motility in ulcerative colitis

    PubMed Central

    Antonelli, Elisabetta; Villanacci, Vincenzo; Baldoni, Monia; Dore, Maria Pina

    2014-01-01

    Background Inflammatory conditions affecting the gut may cause motility disturbances, and ulcerative colitis – one of the main disorders among the inflammatory bowel diseases – may display abnormal colonic motility. Aim To review the abnormalities of the large bowel in ulcerative colitis, by considering the motility, laboratory (in vitro) and pathological studies dealing with this topic. Methods A comprehensive online search of Medline and the Science Citation Index was carried out. Results Patients with ulcerative colitis frequently display colonic motor abnormalities, including lack of contractility, an increase of propulsive contractile waves, an excessive production of nitric oxide, vasoactive intestinal polypeptide nerves, interleukin 1 beta, neurotensin, tachykinins levels and the weaker action of substance P, likely related to a neuromuscular dysfunction due to the inflammatory process. Conclusions A better understanding of the pathophysiological grounds of altered colonic motility in ulcerative colitis may lead to a more in-depth knowledge of the accompanying symptoms and to better and more targeted therapeutic approaches. PMID:25452840

  9. Treatment of experimental ulcerative colitis.

    PubMed

    Lazebnik, L B; Lychkova, A E; Knyazev, O V

    2012-10-01

    The effects of infliximab, an anticytokine drug, on the course of inflammatory process was studied on the model of ulcerative colitis induced by injection of picrylsulfonic acid. Infliximab prevented the development of toxic dilatation and a drop of bioelectric activity of smooth muscles via maintenance of activity of the intramural nervous system neurons. PMID:23113311

  10. 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

  11. 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

  12. 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

  13. [Diagnostic guideline of ulcerative colitis].

    PubMed

    Choi, Chang Hwan; Jung, Sung Ae; Lee, Bo In; Lee, Kang Moon; Kim, Joo Sung; Han, Dong Soo

    2009-03-01

    Ulcerative colitis is a chronic inflammatory disorder causing mucosal inflammation of the colorectum with crypt abnormality on biopsy. It affects the rectum and a variable extent of the colon in continuity. Ulcerative colitis is characterized by a relapsing and remitting course. It arises from an interaction between genetic and environmental factors, but the precise etiology is unknown. The incidence and prevalence in Korea are still low compared with those of Western countries, but have increased in recent years. There are many challenging issues on the diagnosis of ulcerative colitis, and sometimes these lead to differences in practice between clinicians. Therefore, IBD Study Group of KASID set out the Korean diagnostic guideline of ulcerative colitis. The diagnosis is based on clinical, endoscopic, radiologic, and histologic criteria. The symptoms are dependent upon the extent and severity of disease and most commonly include bloody diarrhea, rectal bleeding, and/or urgency. The systemic symptoms of malaise, tachycardia, fever, or weight loss are features of a severe attack. The laboratory findings may reveal leucocytosis, thrombocytosis, iron deficiency anemia, hypoalbuminemia, and elevated erythrocyte sedimentation rate and C-reactive protein indicating severe disease activity or chronicity. For the elimination of infectious causes, microbial investigation with stool specimens should be performed for common enteric pathogens including assays for Clostridium difficile toxin, and sometimes for amoeba or other parasites. The most typical endoscopic features are continuous, confluent, and concentric colonic involvement proximal to the anal verge. Endoscopic severity may be best well reflected by the presence of mucosal friability, spontaneous bleeding, and deep ulcerations. Typical pathologic findings are composed of widespread crypt architectural distortion (cryptitis, crypt abscess, and crypt atrophy), heavy, diffuse lamina propria cell infiltration, and basal

  14. 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

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

    ClinicalTrials.gov

    2016-08-09

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

  16. New insights and challenges in microscopic colitis

    PubMed Central

    2015-01-01

    Microscopic colitis (MC) is described as an inflammatory bowel disease characterized by chronic, bloodless diarrhea with normal or close to normal endoscopic findings. Histopathological examination reveals two subtypes: collagenous colitis (CC) and lymphocytic colitis (LC), which are indistinguishable clinically. The disease debuts typically in middle-aged patients, but can occur at all ages, including children. A female predominance is found in both CC and LC, but is not confirmed by others in LC. The etiology is unclear, but the disease has been assumed to be of autoimmune origin. However, several etiologies may render a microscopic inflammation in the mucosa; this is a common, universal reaction to a variety of irritants in contact with the intestinal lumen. Furthermore, some patients with a microscopic inflammation in their colonic mucosa have no symptoms, or are suffering from constipation or abdominal pain, rather than diarrhea. Recently, a discussion was initiated calling into question the overdiagnosing of symptoms and pointing out the danger of exacerbating people’s perception of their ailments, of weakening their eligibility in health insurance, of overprescription of drugs, and thus the increasing cost to the society of health care. In the light of this discussion, this review will highlight histopathological and clinical features of MC, and discuss the diagnosis and management of this disease. Perhaps, the intestinal mucosa has no other mode by which to react than an inflammatory response, irrespective of the presence or absence of autoimmunity. Thus, to better identify and classify subgroups of MC, and to clarify and correctly handle the inflammatory changes, this field of research stands to benefit from a review of the results and experience gained to date. PMID:25553078

  17. 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

  18. Peculiar Presentation of Ulcerative Colitis

    PubMed Central

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

    2016-01-01

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

  19. Efficacy of Combined Mesalazine Plus Corticosteroid Enemas for Diversion Colitis after Subtotal Colectomy for Ulcerative Colitis

    PubMed Central

    Matsumoto, Satohiro; Mashima, Hirosato

    2016-01-01

    Diversion colitis is a benign inflammatory process that occurs in any part of the large bowel excluded from the fecal stream by a diverting colostomy. While most of the patients with diversion colitis usually are asymptomatic, a minority has abdominal pain and rectal discharge of blood or mucus. A 65-year-old Japanese man was diagnosed as having diversion colitis with ulcerative colitis at 4 months after subtotal colectomy. Corticosteroid and mesalazine enemas were started nonsynchronously. A proctoscopy after 2 months showed no response. Prednisolone injections were started at 1.0 mg/kg daily, but the mucosal inflammation still failed to improve. A combined mesalazine 1 g plus prednisolone sodium phosphate 20 mg enema was started once daily. The rectal bleeding and endoscopic findings improved. Finally proctectomy and ileal pouch-anal anastomosis were successfully performed. A combined mesalazine plus corticosteroid enema may be effective in patients with diversion colitis associated with ulcerative colitis.

  20. 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

  1. Mindfulness May Be Helpful for People with Ulcerative Colitis

    MedlinePlus

    ... supported by NCCAM, was reported in the journal Digestion . Ulcerative colitis is a chronic inflammatory bowel disease ... flare-up in patients with inactive ulcerative colitis . Digestion. 2014;89:142–155. Additional Resources Meditation Information ...

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

    PubMed Central

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole K.

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis. PMID:26798523

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

    PubMed

    Park, Tina; Cave, David; Marshall, Christopher

    2015-08-01

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis. PMID:26269669

  4. Adsorbents as antiendotoxin agents in experimental colitis.

    PubMed Central

    Gardiner, K R; Anderson, N H; McCaigue, M D; Erwin, P J; Halliday, M I; Rowlands, B J

    1993-01-01

    The intestinal mucosa protects the body from a large reservoir of intraluminal pathogenic bacteria and endotoxins. This mucosal barrier is disrupted by the inflammation and ulceration of inflammatory bowel disease and may permit the absorption of toxic bacterial products. Systemic endotoxaemia has been demonstrated in ulcerative colitis and Crohn's disease and correlates with the extent and activity of disease. In this study the efficacy of absorbents as antiendotoxin agents in a hapten induced rat model of colitis is investigated. Induction of colitis was associated with systemic endotoxaemia. Enteral administration of terra fullonica and kaolin, but not of charcoal, significantly reduced systemic endotoxaemia (terra fullonica 4.2 (1.40) pg/ml; kaolin 5.29 (1.86) pg/ml; charcoal 32.7 (16.6) pg/ml; water 39.8 (12.6) pg/ml). Data expressed as mean (SE). With increasing severity of colitis, there was a decreasing ability of adsorbent therapy (terra fullonica) to control systemic endotoxaemia. Enteral administration of adsorbents controls gut derived systemic endotoxaemia in experimental colitis in animals and may be a useful antiendotoxin treatment in patients with inflammatory bowel disease. PMID:8432452

  5. [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

  6. Amyloid Goiter Secondary to Ulcerative Colitis

    PubMed Central

    Aydin, Bunyamin; 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

  7. 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

  8. Cerebral venous thrombosis in ulcerative colitis

    PubMed Central

    Menon, Bindu; Goyal, Rajeev; Nihal, Lalit; Reddy, Rajasekhar

    2013-01-01

    Ulcerative colitis has been reported to show hyper coagulation leading to peripheral and rarely central thrombosis. A 35-year-old female was admitted with chief complaints of increased frequency of bloody diarrhea, abdominal pain, and weight loss for 2 months. The patient was diagnosed to have ulcerative colitis after sigmoidoscopy and biopsy and she was started on treatment. Two days later, the patient developed headache and seizures. Magnetic resonance imaging of brain showed cerebral venous thrombosis with venous infarcts. A high index of clinical suspicion is needed to diagnose this uncommon condition so that appropriate treatment can be initiated. PMID:23546367

  9. 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.

  10. Fecal calprotectin and ulcerative colitis endoscopic activity index as indicators of mucosal healing in ulcerative colitis.

    PubMed

    Taghvaei, Tarang; Maleki, Iradj; Nagshvar, Farshad; Fakheri, Hafez; Hosseini, Vahid; Valizadeh, Seyed Mohammad; Neishaboori, Hassan

    2015-04-01

    Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory large bowel disease with recurrent variable periods of exacerbation. The aim of the current study is to evaluate the correlation of UCEIS with fecal calprotectin (FC) level to assess disease activity in UC patients in order to determine whether FC can prognosticate clinical outcome and disease activity of UC instead of colonoscopic evaluation. Our endoscopic investigations revealed the extension of UC as the following: proctitis (11.6%), procto-sigmoiditis (18.5%), left-sided colitis (15.8%), extensive colitis (11.7%), and normal endoscopy (42.4%). Conclusively, we suggest that FC can be used as a reliable tool to evaluate disease activity in ulcerative colitis patients. Moreover, our findings indicate a significant correlation between FC level and mucosal healing. PMID:25366383

  11. Why do patients with ulcerative colitis relapse?

    PubMed

    Riley, S A; Mani, V; Goodman, M J; Lucas, S

    1990-02-01

    To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis. PMID:2311975

  12. Selenoprotein P in colitis-associated carcinoma

    PubMed Central

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

    2016-01-01

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

  13. Rectal mucocoele following subtotal colectomy for colitis

    PubMed Central

    Day, N; Walsh, C

    2014-01-01

    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. PMID:25198962

  14. Rectocolectomy with anal conservation in inflammatory colitis

    PubMed Central

    Deane, A M; Celestin, L R

    1983-01-01

    Eleven patients with inflammatory colitis underwent total colectomy and rectal excision with conservation of the anus. This is a lesser procedure than proctocolectomy and achieves total extirpation of diseased large-bowel mucosa. ImagesFig. 1Fig. 2 PMID:6824297

  15. 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

  16. Surveillance colonoscopy for colitis-associated dysplasia and cancer in ulcerative colitis patients.

    PubMed

    Hata, Keisuke; Kishikawa, Junko; Anzai, Hiroyuki; Shinagawa, Takahide; Kazama, Shinsuke; Ishii, Hiroaki; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Tanaka, Junichiro; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2016-04-01

    Long-standing ulcerative colitis patients are known to be at high risk for the development of colorectal cancer. Therefore, surveillance colonoscopy has been recommended for these patients. Because colitis-associated colorectal cancer may be difficult to identify even by colonoscopy, a random biopsy method has been recommended. However, the procedure of carrying out a random biopsy is tedious and its effectiveness has also not yet been demonstrated. Instead, targeted biopsy with chromoendoscopy has gained popularity in European and Asian countries. Chromoendoscopy is generally considered to be an effective tool for ulcerative colitis surveillance and is recommended in the guidelines of the British Society of Gastroenterology and the European Crohn's and Colitis Organisation. Although image-enhanced endoscopy, such as narrow-band imaging and autofluorescence imaging, has been investigated as a potential ulcerative colitis surveillance tool, it is not routinely applied for ulcerative colitis surveillance in its present form. The appropriate intervals of surveillance colonoscopy have yet to be determined. Although the Japanese and American guidelines recommend annual or biannual colonoscopy, the British Society of Gastroenterology and the European Crohn's and Colitis Organisation stratified their guidelines according to the risks of colorectal cancer. A randomized controlled trial comparing random and targeted biopsy methods has been conducted in Japan and although the final analysis is still ongoing, the results of this study should address this issue. In the present review, we focus on the current detection methods and characterization of dysplasia/cancer and discuss the appropriate intervals of colonoscopy according to the stratified risks. PMID:26096182

  17. 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

  18. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis

    PubMed Central

    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

    2013-01-01

    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+CD45RBhi 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. PMID:23945234

  19. Varied Clinical Manifestations of Amebic Colitis.

    PubMed

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

    2015-11-01

    Invasive amebiasis is common worldwide, but infrequently observed in the United States. It is associated with considerable morbidity in patients residing in or traveling to endemic areas. We review the clinical and endoscopic manifestations of amebic colitis to alert physicians to the varied clinical manifestations of this potentially life-threatening disease. Copyright ©Most patients present with watery or bloody diarrhea. Less common presentations of amebic colitis include abdominal pain, overt gastrointestinal bleeding, exacerbation of inflammatory bowel disease, or the incidental association with colon cancer. Amebic liver abscesses are the most frequent complication. Rectosigmoid involvement may be found on colonoscopy; however, most case series have reported that the cecum is the most commonly involved site, followed by the ascending colon. Endoscopic evaluation should be used to assist in the diagnosis, with attention to the observation of colonic inflammation, ulceration, and amebic trophozoites on histopathological examination. PMID:26539949

  20. Intractable colitis associated with chronic granulomatous disease.

    PubMed

    Arimura, Yoshiaki; Goto, Akira; Yamashita, Kentaro; Endo, Takao; Ikeda, Hideyuki; Tanaka, Kaori; Tsutsumi, Hiroyuki; Shinomura, Yasuhisa; Imai, Kohzoh

    2006-11-01

    The case of a 20-year-old Japanese man, diagnosed as having autosomal recessive chronic granulomatous disease (CGD), who was being treated with corticosteroids for intractable unclassified colitis, is described. He died from multiple organ failure following disseminated intravascular coagulation secondary to disseminated varicella-zoster virus (VZV) infection. He was diagnosed as an index case of CGD when 2 years old, was inoculated against VZV at the age of 5 years and had had an unremarkable course for 19 years. He was admitted to hospital because of a third episode of recurrent bloody diarrhoea. Clinical remission for each episode was achieved by intravenous corticosteroid therapy. Unclassified colitis associated with CGD was diagnosed based on a colonic biopsy demonstrating characteristic macrophages with lipofuscin deposits. From a treatment viewpoint, idiopathic inflammatory bowel disease (IBD) should be differentiated from secondary IBD occurring in CGD, in which immunosuppressive drugs including corticosteroids, still the mainstay of IBD treatment, should be avoided. PMID:17030921

  1. Histiocytic ulcerative colitis in a Boxer dog.

    PubMed

    Hill, F W; Sullivan, N D

    1978-09-01

    A 2-year-old male Boxer dog had passed loose faeces mixed with fresh blood and mucus for 8 months. Tenesmus after defaecation was a feature. Colitis was diagnosed from the proctoscopic appearance of the recto-colonic mucosa and confirmed from a biopsy. The disorder proved unresponsive to sulphasalazine therapy, but oral chloramphenicol, betamethasone and prednisolone enemas administered over a 6-week period produced a satisfactory clinical improvement, which persisted for a further 3 weeks without treatment. However, follow-up proctoscopy showed only a marginal improvement in the appearance of the mucosa and appeared to exacerbate further bloody diarrhoea, which persisted. The dog was destroyed and histiocytic ulcerative colitis confirmed at autopsy. PMID:743058

  2. Pyostomatitis vegetans. Clinical marker of ulcerative colitis.

    PubMed

    Lopez-Jornet, P; Gomez-Garcia, F; Camacho-Alonso, F

    2012-03-01

    Pyodermatitis-pyostomatitis vegetans (PV), a rare disorder of the skin and oral mucosa, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. We have presented the case of a patient with PV. This report emphasizes the relationship of PV to inflammatory bowel disease and the importance of the oral lesions as initial presenting signs of systemic disease or activity. PMID:22685913

  3. 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

  4. Herpes simplex virus colitis in a neonate.

    PubMed

    Daley, Andrew J; Craven, Paul; Holland, Andrew J A; Jones, Cheryl A; Badawi, Nadia; Isaacs, David

    2002-09-01

    Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life. PMID:12380594

  5. Animal Models of Colitis-Associated Carcinogenesis

    PubMed Central

    Kanneganti, Manasa; Mino-Kenudson, Mari; Mizoguchi, Emiko

    2011-01-01

    Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC), especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs) and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future. PMID:21274454

  6. 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

  7. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

    PubMed

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

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments. PMID:26246013

  8. Herpes simplex virus colitis complicating ulcerative colitis: A case report and brief review on superinfections.

    PubMed

    Schunter, Marco Oliver; Walles, Thorsten; Fritz, Peter; Meyding-Lamadé, Uta; Thon, Klaus-Peter; Fellermann, Klaus; Stange, Eduard Friedrich; Lamadé, Wolfram

    2007-09-01

    In patients with inflammatory bowel disease herpes simplex virus infection has been described as a major cause of morbidity and mortality, especially in immunocompromised individuals. Here we present the case of a 35-year old woman with an exacerbation of ulcerative colitis caused by herlpes simplex virus infection (HSV-2). The diagnosis was confirmed histologically following subtotal colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative hematochezia stopped. Herpes simplex virus colitis is a rare but potentially fatal complication of immunosuppressive treatment in patients with inflammatory bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to improve prognosis. PMID:21172183

  9. Fulminant herpes colitis in a patient with Crohn's disease.

    PubMed

    el-Serag, H B; Zwas, F R; Cirillo, N W; Eisen, R N

    1996-04-01

    Herpes simplex virus (HSV) is a well-recognized cause of gastrointestinal infection, most commonly in patients with underlying immunodeficiency. The esophagus, perianum, and rectum are the most common sites of involvement; however, extensive colitis is rare. We describe a woman with Crohn's disease who developed pathologically proven HSV colitis. We review the literature and present the possible implications of the diagnosis. PMID:8724263

  10. 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

  11. 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

  12. 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. PMID:24895387

  13. Acute ischaemic colitis associated with oral phenylephrine decongestant use

    PubMed Central

    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. PMID:24895387

  14. Temporal Comorbidity of Mental Disorder and Ulcerative Colitis

    PubMed Central

    Cawthorpe, David; Davidson, Marta

    2015-01-01

    Objectives: Ulcerative colitis is an inflammatory bowel disease that rarely exists in isolation in affected patients. We examined the association of ulcerative colitis and International Classification of Diseases mental disorder, as well as the temporal comorbidity of three broad International Classification of Diseases groupings of mental disorders in patients with ulcerative colitis to determine if mental disorder is more likely to occur before or after ulcerative colitis. Methods: We used physician diagnoses from the regional health zone of Calgary, Alberta, for patient visits from fiscal years 1994 to 2009 for treatment of any presenting concern in that Calgary health zone (763,449 patients) to identify 5113 patients age younger than 1 year to age 92 years (2120 males, average age = 47 years; 2993 females, average age = 48 years) with a diagnosis of ulcerative colitis. Results: The 16-year cumulative prevalence of ulcerative colitis was 0.0058%, or 58 cases per 10,000 persons (95% confidence interval = 56–60 per 10,000). Although the cumulative prevalence of mental disorder in the overall sample was 5390 per 10,000 (53.9%), we found that 4192 patients with ulcerative colitis (82%) also had a diagnosis of a mental disorder. By annual rate of ulcerative colitis, patients with mental disorder had a significantly higher annual prevalence. The mental disorder grouping neuroses/depressive disorders was most likely to arise before ulcerative colitis (odds ratio = 1.87 for males; 2.24 for females). Conclusions: A temporal association was observed between specific groups of International Classification of Diseases mental disorder and ulcerative colitis, indicating a possible etiologic relationship between the disorders or their treatments, or both. PMID:25663206

  15. Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer.

    PubMed

    Das, S; Rachagani, S; Sheinin, Y; Smith, L M; Gurumurthy, C B; Roy, H K; Batra, S K

    2016-05-19

    MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model. PMID:26364605

  16. Crohn's and colitis in children and adolescents.

    PubMed

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

    2012-11-01

    Crohn's disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn's disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn's disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn's disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications. PMID:23139601

  17. Cerebral venous thrombosis revealing an ulcerative colitis

    PubMed Central

    Taous, Abdellah; Berri, Maha Aït; Lamsiah, Taoufik; Zainoun, Brahim; Ziadi, Tarik; Rouimi, Abdelhadi

    2016-01-01

    Cerebral venous thrombosis (CVT) has been reported as an uncommon and devastating complication of ulcerative colitis (UC), with an annual incidence varying between 0,5 to 6,7%. It is suspected to be a consequence of the hypercoagulable state occurring during disease relapse. We report a case of 22-year-old female patient presenting with CVT revealing an UC. Our case raises the awareness among health professionals about the inflammatory bowel diseases (IBD) as a rare etiology of CVT, and signifies the importance of considering antithrombotic prophylaxis in all hospitalised IBD patients, especially those with active disease. PMID:27279947

  18. 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

  19. Serum antibodies to Escherichia coli in subjects with ulcerative colitis

    PubMed Central

    Heddle, R. J.; Shearman, D. J. C.

    1979-01-01

    It has been proposed that in ulcerative colitis the intestinal flora stimulates autoimmune reactions to colonic epithelium through shared specificities exposed in a `common antigen' found in most Enterobacteriaceae. The present experiments aimed to resolve conflicting data as to whether patients with ulcerative colitis have selectively increased serum antibody titres to enterobacterial common antigen or E. coli 014, which is rich in enterobacterial common antigen. Antibody titres to enterobacterial common antigen and lipopolysaccharides of E. coli 014 and of five serotypes of E. coli which occur frequently in human faeces were measured by passive haemagglutination. Sera were obtained from patients with ulcerative colitis, age- and sex-matched controls and subjects with other gastrointestinal disorders. Serum titres to enterobacterial common antigen and E. coli 014 lipopolysaccharide were not increased significantly in subjects with ulcerative colitis but significant increases were observed in subjects with chronic liver disease without colitis. Patients with active ulcerative colitis, patients with chronic liver disease and subjects convalescent from Salmonella or Shigella infections all had significantly increased serum titres to the antigens as a group. Class-specific enhancement of passive haemagglutination indicated that the class distribution of serum antibodies was similar in subjects with ulcerative colitis and controls. PMID:93528

  20. Grim19 Attenuates DSS Induced Colitis in an Animal Model

    PubMed Central

    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. PMID:27258062

  1. Intestinal permeability and contractility in murine colitis.

    PubMed Central

    van Meeteren, M E; van Bergeijk, J D; van Dijk, A P; Tak, C J; Meijssen, M A; Zijlstra, F J

    1998-01-01

    We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated. PMID:9705603

  2. [Surgery of ulcerative colitis using ileoanal anastomosis].

    PubMed

    Utsunomiya, J; Oota, M; Matsumoto, M; Natori, H

    1985-09-01

    The ideal surgical treatment for ulcerative colitis is the ileoanal anastomosis (IAA), which, however, is not yet generally accepted as a practical procedure because of a suboptimal fecal function, frequent postoperative complications and technical difficulties. Based on one (U.) of the authors experiences on 36(34) polyposis and 19(12) colitis (paracentesis indicate the number of cases in (U.)'s previous appointment, Tokyo Medical and Dental University, 1977-1983). The practical procedure of IAA can be achieved by combining the following basic principles; a direct anastomosis of J-shape ileal pouch to the anal sphincteric mechanism, temporarily exclusion of the anastomosis by a loop-ileostomy, mucosectomy confined to the lower rectum leaving the short muscular cuff, and meticulous dissection of inflamed mucosa of the anal canal minimizing the damage to the internal sphincter which is achieved by the prone ano-abdominal approach. At elective operation, the procedure can be performed either as primary surgery or as the secondary following rectum preserving operation, in which, coeco-rectal anastomosis is advisable for preserving the ileocolic vessels that is helpful for J-pouch construction. In emergency surgical program, IAA is still be preserved as a final restructive surgery following colectomy with an open rectal exclusion or Turnbull' s total colonic exclusion. In this occasion, an ascendicostomy is advisable for preserving the ileocolic vessels. PMID:4088260

  3. 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. PMID:25876561

  4. Ileorectal Anastomosis and Proctocolectomy with End Ileostomy for Ulcerative Colitis

    PubMed Central

    Moreira, Andre da Luz; Lavery, Ian C.

    2010-01-01

    Until the development of the ileal pouch-anal anastomosis in the early 1980s, proctocolectomy with end ileostomy was the only definitive surgery for ulcerative colitis and colectomy with ileorectal anastomosis was the procedure of choice for affected patients who were reluctant to have a permanent ileostomy. Currently, ileal pouch-anal anastomosis is the most common procedure for patients with ulcerative colitis requiring surgical treatment. However, there is still a role for ileorectal anastomosis and proctocolectomy with end ileostomy for a selected group of patients. In this review, the authors summarize the current indications for ileorectal anastomosis and proctocolectomy with end ileostomy in patients with ulcerative colitis. PMID:22131897

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

    PubMed

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

    1994-01-01

    Ultrasonic signs of colitis were studied in 24 adults aged 20 to 53 yr and 38 children aged 3-16 yr in whom chronic colitis was diagnosed. 2 adults and three children had ulcerative colitis. The results obtained showed that with the aid of echography it is possible to detect inflammatory lesions in the large intestine as well as to observe the time course of changes in its wall during the course of treatment. Ultrasonic investigation can be of screening type in detecting an inflammatory process in the large intestine, on the one hand, and a method of profound study of changes in its wall, on the other. PMID:7831876

  6. Cytomegalovirus Colitis: An Uncommon Mimicker of Common Colitides.

    PubMed

    Baniak, Nick; Kanthan, Rani

    2016-08-01

    Cytomegalovirus latency, though ubiquitous in the human population, is known to cause colitis in both immunocompromised and immunocompetent hosts. Furthermore, the clinical, endoscopic, and histologic appearance of cytomegalovirus colitis can mimic that of inflammatory bowel disease, an extremely well-documented disease. In this context, though many reports have looked at inflammatory bowel disease with superimposed cytomegalovirus infection, less attention has been paid to cytomegalovirus as a primary cause of isolated colitis. Owing to the rarity of this phenomenon, it is important to consider this diagnosis and implement proper testing to avoid misdiagnosis and mismanagement. PMID:27472242

  7. Characterization of colonic cellular glycoconjugates in colitis and cancer-prone tamarins versus colitis and cancer-resistant primates.

    PubMed Central

    Moore, R.; King, N.; Alroy, J.

    1988-01-01

    Differences in colonic secretory glycoconjugates (ie, mucin) between normal and ulcerative colitis-prone patients have been noted. Similar differences may occur in a corresponding primate model, the cotton-top tamarin (CTT), Saguinus oedipus, a New World monkey which suffers from spontaneous chronic colitis and colon cancer. Lectin reagents were used to characterize and compare colonic cell surface, cytoplasmic, and secretory glycoconjugates of 9 clinically healthy cotton-top tamarins, 7 colitis-susceptible, cancer-resistant tamarins (Callithrix jacchus, Saguinus fuscicollis), and 8 colitis and cancer-resistant primates (Aotus trivirgatus, Saimiri sciureus, Macaca fascicularis, and Macaca mulatta). Paraffin-embedded colonic sections were labeled with ten different biotinylated lectins and visualized by the avidin-biotin peroxidase (ABC) method. Significant differences were demonstrated in the pattern of lectin staining between the colitis-resistant and colitis-prone groups of primates. The differences were noted with Griffonia simplicifolia-I (GS-I), Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) before and after neuraminidase, Ricinus communis agglutinin-I (RCA-I), soybean agglutinin (SBA), Ulex europaeus agglutinin-I (UEA-I), wheat germ agglutinin (WGA), and succinylated WGA (S-WGA). Significant differences between the CTT and phylogenetically related colitis-prone but cancer-resistant tamarins were demonstrated with SBA, UEA-I, and PNA after desialylation with neuraminidase. These results suggest that differences in colonic cellular glycoconjugates between colitis- and cancer-susceptible species versus colitis-susceptible, cancer-resistant species may be associated with risk of cancer. Images Figure 2 PMID:3132857

  8. Characterization of colonic cellular glycoconjugates in colitis and cancer-prone tamarins versus colitis and cancer-resistant primates.

    PubMed

    Moore, R; King, N; Alroy, J

    1988-06-01

    Differences in colonic secretory glycoconjugates (ie, mucin) between normal and ulcerative colitis-prone patients have been noted. Similar differences may occur in a corresponding primate model, the cotton-top tamarin (CTT), Saguinus oedipus, a New World monkey which suffers from spontaneous chronic colitis and colon cancer. Lectin reagents were used to characterize and compare colonic cell surface, cytoplasmic, and secretory glycoconjugates of 9 clinically healthy cotton-top tamarins, 7 colitis-susceptible, cancer-resistant tamarins (Callithrix jacchus, Saguinus fuscicollis), and 8 colitis and cancer-resistant primates (Aotus trivirgatus, Saimiri sciureus, Macaca fascicularis, and Macaca mulatta). Paraffin-embedded colonic sections were labeled with ten different biotinylated lectins and visualized by the avidin-biotin peroxidase (ABC) method. Significant differences were demonstrated in the pattern of lectin staining between the colitis-resistant and colitis-prone groups of primates. The differences were noted with Griffonia simplicifolia-I (GS-I), Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) before and after neuraminidase, Ricinus communis agglutinin-I (RCA-I), soybean agglutinin (SBA), Ulex europaeus agglutinin-I (UEA-I), wheat germ agglutinin (WGA), and succinylated WGA (S-WGA). Significant differences between the CTT and phylogenetically related colitis-prone but cancer-resistant tamarins were demonstrated with SBA, UEA-I, and PNA after desialylation with neuraminidase. These results suggest that differences in colonic cellular glycoconjugates between colitis- and cancer-susceptible species versus colitis-susceptible, cancer-resistant species may be associated with risk of cancer. PMID:3132857

  9. 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. PMID:26279300

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Medical Therapy of Active Ulcerative Colitis

    PubMed Central

    Bürger, Martin; Schmidt, Carsten; Teich, Niels; Stallmach, Andreas

    2015-01-01

    Summary Background Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. Methods A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. Results In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. Conclusion There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options. PMID:26557831

  15. 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

  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 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

  17. 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...

  18. 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

  19. The NLRP1 Inflammasome Attenuates Colitis and Colitis-Associated Tumorigenesis1

    PubMed Central

    Williams, Tere M.; Leeth, Rachel A.; Rothschild, Daniel E.; Coutermarsh-Ott, Sheryl L.; McDaniel, Dylan K.; Simmons, Alysha E.; Heid, Bettina; Cecere, Thomas E.; Allen, Irving C.

    2015-01-01

    NLR proteins are a diverse family of pattern recognition receptors that are essential mediators of inflammation and host defense in the gastrointestinal system. Recent studies have identified a sub-group of inflammasome forming NLRs that modulate the mucosal immune response during inflammatory bowel disease (IBD) and colitis associated tumorigenesis. To better elucidate the contribution of NLR family members in IBD and cancer, we conducted a retrospective analysis of gene expression metadata from human patients. These data revealed that NLRP1, an inflammasome forming NLR, was significantly dysregulated in IBD and colon cancer. To better characterize the function of NLRP1 in disease pathogenesis, we utilized Nlrp1b−/− mice in colitis and colitis associated cancer models. Here, we report that NLRP1 attenuates gastrointestinal inflammation and tumorigenesis. Nlrp1b−/− mice demonstrated significant increases in morbidity, inflammation and tumorigenesis compared to wild type animals. Similar to data previously reported for related inflammsome forming NLRs, the increased inflammation and tumor burden was correlated with attenuated levels of IL-1β and IL-18. Further mechanistic studies utilizing bone marrow reconstitution experiments revealed that the increased disease pathogenesis in the Nlrp1b−/− mice was associated with non-hematopoietic derived cells and suggests that NLRP1 functions in the colon epithelial cell compartment to attenuate tumorigenesis. Together, these data identify NLRP1 as an essential mediator of the host immune response during IBD and cancer. These findings are consistent with a model whereby multiple NLR inflammasomes attenuate disease pathobiology through modulating IL-1β and IL-18 levels in the colon. PMID:25725098

  20. The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis.

    PubMed

    Williams, Tere M; Leeth, Rachel A; Rothschild, Daniel E; Coutermarsh-Ott, Sheryl L; McDaniel, Dylan K; Simmons, Alysha E; Heid, Bettina; Cecere, Thomas E; Allen, Irving C

    2015-04-01

    Nucleotide-binding domain and leucine-rich repeat (NLR) proteins are a diverse family of pattern recognition receptors that are essential mediators of inflammation and host defense in the gastrointestinal system. Recent studies have identified a subgroup of inflammasome forming NLRs that modulate the mucosal immune response during inflammatory bowel disease (IBD) and colitis associated tumorigenesis. To better elucidate the contribution of NLR family members in IBD and cancer, we conducted a retrospective analysis of gene expression metadata from human patients. These data revealed that NLRP1, an inflammasome forming NLR, was significantly dysregulated in IBD and colon cancer. To better characterize the function of NLRP1 in disease pathogenesis, we used Nlrp1b(-/-) mice in colitis and colitis-associated cancer models. In this paper, we report that NLRP1 attenuates gastrointestinal inflammation and tumorigenesis. Nlrp1b(-/-) mice demonstrated significant increases in morbidity, inflammation, and tumorigenesis compared with wild-type animals. Similar to data previously reported for related inflammasome forming NLRs, the increased inflammation and tumor burden was correlated with attenuated levels of IL-1β and IL-18. Further mechanistic studies using bone marrow reconstitution experiments revealed that the increased disease pathogenesis in the Nlrp1b(-/-) mice was associated with nonhematopoietic-derived cells and suggests that NLRP1 functions in the colon epithelial cell compartment to attenuate tumorigenesis. Taken together, these data identify NLRP1 as an essential mediator of the host immune response during IBD and cancer. These findings are consistent with a model whereby multiple NLR inflammasomes attenuate disease pathobiology through modulating IL-1β and IL-18 levels in the colon. PMID:25725098

  1. 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

  2. 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

  3. 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

  4. 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

  5. Cytomegalovirus Colitis in a Burn Patient.

    PubMed

    Gibbs, Jeff T; Zieger, Madeline; Sood, Rajiv

    2016-01-01

    The prevalence of cytomegalovirus in the burn population is high. However, its role in the clinical management of burn patients is still being defined. This report documents a 41-year-old man who developed cytomegalovirus (CMV) colitis after being admitted with a 72% burn. Before the administration of ganciclovir, the authors had difficulty controlling his quantitative wound cultures with serial debridements, topical agents, and systemic antibiotics for known pathogens, which led to graft loss. After the ganciclovir was given, his quantitative wound cultures improved without changing the authors' topical agents or systemic antibiotics and had improved graft take. Whether CMV infection alone contributed to an increased morbidity in this patient or the combination of bacteria/fungal infection with CMV led to a synergistic effect is still not clearly understood. CMV may have contributed to a dysfunction in his cell mediated immunity, which, in turn, lowered the bacterial and fungal load necessary to cause graft loss. Patients who continue to do poorly despite adequate treatment for known pathogens may need to be screened for CMV and treated. PMID:26056763

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

    PubMed Central

    Zundler, Sebastian; Neurath, Markus F.

    2016-01-01

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

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

    PubMed

    Zundler, Sebastian; Neurath, Markus F

    2016-01-01

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

  8. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

    PubMed Central

    Hirayama, Yutaka; Ando, Takafumi; Hirooka, Yoshiki; Watanabe, Osamu; Miyahara, Ryoji; Nakamura, Masanao; Yamamura, Takeshi; Goto, Hidemi

    2016-01-01

    AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus (CMV)-associated colitis in patients with active ulcerative colitis (UC). METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis. RESULTS: Multivariate analysis indicated independent associations with the extent of disease (pancolitis) and use of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC (odds ratio = 12.672, 95%CI: 4.210-38.143). CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC. PMID:27014426

  9. 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

  10. 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

  11. Endoscopic Characteristics of the Healing Process of Ulcerative Colitis

    PubMed Central

    Kishi, Hideyuki

    1998-01-01

    This study compared the histologic characteristics of ulcerative colitis with findings on conventional colonoscopy and on magnification and dye application for 70 sites that underwent biopsy. The primary objective was to study the correspondence between histologic findings and endoscopic findings with respect to glandular restructuring and the resolution of inflammation from the active to the remission phase of ulcerative colitis. Widened grooves, as assessed by the endoscopic staining technique and magnified observation, most closely correlated with histologic evidence of resolution of inflammation, and vascular markings and color tone of the mucosa on general colonoscopy most closely correlated with histologic evidence of glandular restructuring, such as glandular maturity. Magnifying endoscopy after dye application, in addition to conventional endoscopy, is therefore considered essential in the evaluation of ulcerative colitis during the resolving phase. PMID:18493478

  12. [Meloxicam-induced colitis revealed by acute abdominal pain].

    PubMed

    Seddik, H; Rabhi, M

    2013-03-01

    Whether intestinal toxicity of preferential or selective COX-2 inhibitors is reduced compared with that of standard NSAIDs is controversial. A 26-year-old woman presented with acute abdominal pain and bloody diarrhoea a few days after beginning meloxicam treatment. Endoscopic examination of the colon showed erythematous and ulcerative lesions involving 15 cm of the left colon. No aetiology has been found for colitis. Diarrhea disappeared 1 week after meloxicam was stopped. Total colonoscopy 3 months and 2 years later was normal. The role of meloxicam in the etiology of colitis was considered plausible. This report and a few other cases in the literature suggest that cyclooxygenase-2 selective non-steroidal anti-inflammatory drug inhibitor toxicity should be investigated in case of unexplained acute colitis. PMID:23537413

  13. 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

  14. The Role of CXCR3 in DSS-Induced Colitis

    PubMed Central

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

    2014-01-01

    Inflammatory bowel disease (IBD) is a group of disorders that are characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the aetiopathogenesis is poorly understood, it is widely believed that IBD stems from a dysregulated immune response towards otherwise harmless commensal bacteria. Chemokines induce and enhance inflammation through their involvement in cellular trafficking. Reducing or limiting the influx of these proinflammatory cells has previously been demonstrated to attenuate inflammation. CXCR3, a chemokine receptor in the CXC family that binds to CXCL9, CXCL10 and CXCL11, is strongly overexpressed in the intestinal mucosa of IBD patients. We hypothesised that CXCR3 KO mice would have impaired cellular trafficking, thereby reducing the inflammatory insult by proinflammatory cell and attenuating the course of colitis. To investigate the role of CXCR3 in the progression of colitis, the development of dextran sulfate sodium (DSS)-induced colitis was investigated in CXCR3−/− mice over 9 days. This study demonstrated attenuated DSS-induced colitis in CXCR3−/− mice at both the macroscopic and microscopic level. Reduced colitis correlated with lower recruitment of neutrophils (p = 0.0018), as well as decreased production of IL-6 (p<0.0001), TNF (p = 0.0038), and IFN-γ (p = 0.0478). Overall, our results suggest that CXCR3 plays an important role in recruiting proinflammatory cells to the colon during colitis and that CXCR3 may be a therapeutic target to reduce the influx of proinflammatory cells in the inflamed colon. PMID:24992040

  15. Report of a Rare Case of Nasal Mucosa Pyoderma Vegetans in a Patient with Ulcerative Colitis

    PubMed Central

    Vahedi, Homayoon; Nozari, Neda; Sotoudeh, Masoud

    2015-01-01

    Some dermatologic manifestations are common in ulcerative colitis (UC). Herein, we present a 36-year-old woman with ulcerative colitis and uncommon nasal mucosa pyoderma vegetans. The patient presented to our hospital with symptoms of active colitis and a concomitant 3×4×5 cm dermato-mucosal lesion in her left nasal lumen. After surgery of the mucosal lesion, the treatment for her active colitis was initiated with intravenous infliximab and oral asacol. After a 1-year follow-up, no sign of recurrence favoring mucosal lesion was noted and symptoms of ulcerative colitis were managed properly. PMID:26106471

  16. The Role of Neuropeptides in Mouse Models of Colitis.

    PubMed

    Padua, David; Vu, John P; Germano, Patrizia M; Pisegna, Joseph R

    2016-06-01

    Inflammatory bowel disease (IBD) constitutes an important clinically significant condition that results in morbidity and mortality. IBD can be generally classified into either ulcerative colitis (UC) or Crohn's disease (CD) that differs in the clinical and histopathology. The role of neuropeptides in the pathogenesis of these conditions is becoming increasingly recognized for their importance in modulating the inflammatory state. Animal models provide the greatest insight to better understand the pathophysiology of both disorders which will hopefully allow for improved treatment strategies. This review will provide a better understanding of the role of murine models for studying colitis. PMID:26646243

  17. 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. PMID:17878507

  18. A case of herpes zoster associated with colitis.

    PubMed

    Okimura, H; Muto, M; Ichimiya, M; Mogami, S; Takahata, H; Asagami, C

    1996-09-01

    A 58-year-old Japanese woman who had herpes zoster in association with colitis was successfully treated with intravenously administrated acyclovir. Vesicular lesions with red haloes ranged from the left side of her buttock to the left extremity, corresponding to the L4 to S2 dermatomes. Her colitis was considered to have been induced by varicella-zoster virus, based on the facts that the clinical courses were correlated and that the innervation of the affected site of the colon corresponded to an infected dermatome (S2). PMID:8916665

  19. Refractory ulcerative colitis and iatrogenic colorectal Kaposi's sarcoma.

    PubMed

    Girelli, C M; Serio, G; Rocca, E; Rocca, F

    2009-02-01

    Colorectal Kaposi's sarcoma, a human herpes virus-8 associated mesenchymal tumour, is exceedingly rare in human immunodeficiency virus-negative subjects and almost always reported in association with severe, refractory, inflammatory bowel disease. In this paper we report a case--the second from Italy--of a colorectal Kaposi's sarcoma in a human immunodeficiency virus-negative, heterosexual man with severe refractory ulcerative colitis. Kaposi's sarcoma developed after starting glucocorticosteroid therapy, supporting the theory that colorectal Kaposi's sarcoma associated with ulcerative colitis is iatrogenic. PMID:18054849

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

    PubMed

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

    2010-03-28

    Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors. PMID:20333798

  1. [Neutrophilic dermatosis in ulcerative colitis occurring in advanced age].

    PubMed

    López Maldonado, M D; Calvo Catalá, J; Ronda Gasulla, A; Hortelano Martínez, E; Herrera Ballester, A; Febrer Bosch, I

    1994-08-01

    The Neutrophilic dermatosis (ND) is considered as an independent entity with diverse clinical manifestations among which there are: gangrenous pyoderma, nodous erythema, Sweets Syndrome, vesiculopustula eruptions associated to ulcerous colitis and intestinal short circuit syndrome with or without short circuit. Histologically, they are characterized by infiltration of polymorphonuclear neutrophils, generally at the dermic level, but also at the epidermic. They are usually associated to systemic diseases, especially to chronic intestinal inflammatory disease. Our aim was to describe two forms of clinical presentation of neutrophilic dermatosis: gangrenous pyoderma and vesiculopustula eruption, associated to ulcerous colitis starting at advances ages. PMID:7772690

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

    PubMed Central

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

    2014-01-01

    The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism. PMID:24955172

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

    PubMed

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

    2014-01-01

    The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism. PMID:24955172

  4. Managing osteoporosis in ulcerative colitis: Something new?

    PubMed Central

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

    2014-01-01

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

  5. 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

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

    PubMed Central

    Shi, Xuan-Zheng; Winston, John H.

    2011-01-01

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

  7. 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

  8. 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...

  9. CCR9 Antagonists in the Treatment of Ulcerative Colitis

    PubMed Central

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

    2015-01-01

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

  10. Soluble CD83 ameliorates experimental colitis in mice.

    PubMed

    Eckhardt, J; Kreiser, S; Döbbeler, M; Nicolette, C; DeBenedette, M A; Tcherepanova, I Y; Ostalecki, C; Pommer, A J; Becker, C; Günther, C; Zinser, E; Mak, T W; Steinkasserer, A; Lechmann, M

    2014-07-01

    The physiological balance between pro- and anti-inflammatory processes is dysregulated in inflammatory bowel diseases (IBD) as in Crohn's disease and ulcerative colitis. Conventional therapy uses anti-inflammatory and immunosuppressive corticosteroids to treat acute-phase symptoms. However, low remission rate and strong side effects of these therapies are not satisfying. Thus, there is a high medical need for new therapeutic strategies. Soluble CD83, the extracellular domain of the transmembrane CD83 molecule, has been reported to have interesting therapeutic and immunosuppressive properties by suppressing dendritic cell (DC)-mediated T-cell activation and inducing tolerogenic DCs. However, the expression and function of CD83 in IBD is still unknown. Here, we show that CD83 expression is upregulated by different leukocyte populations in a chemical-induced murine colitis model. Furthermore, in this study the potential of sCD83 to modulate colitis using an experimental murine colitis model was investigated. Strikingly, sCD83 ameliorated the clinical disease symptoms, drastically reduced mortality, and strongly decreased inflammatory cytokine expression in mesenteric lymph nodes and colon. The infiltration of macrophages and granulocytes into colonic tissues was vigorously inhibited. Mechanistically, we could show that sCD83-induced expression of indolamine 2,3-dioxygenase is essential for its protective effects. PMID:24424524

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

    PubMed

    Olsen, Ida Østrup; 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

  12. 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

  13. 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)

  14. Familial cutaneous photosensitivity and colitis with lethal outcome.

    PubMed Central

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

    1991-01-01

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

  15. 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

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. Altered response to hydrogen sulphide during experimental colitis in rats.

    PubMed

    Steidle, J; Würner, L; Diener, M

    2012-09-10

    Hydrogen sulphide (H(2) S) is produced in the intestine by sulphate-reducing bacteria and during metabolism of L-cysteine within the mucosa. This gasotransmitter induces anion secretion by stimulating enteric neurons and by a direct effect on epithelial cells. As H(2) S is discussed to exert both pro- and anti-inflammatory actions, we aimed to investigate the role of H(2) S during experimental colitis by comparing the effects of blockade of H(2) S-forming endogenous enzymes with the effect of a S-reduced diet to diminish microbial production of H(2) S. Rectal application of trinitrobenzenesulfonic acid (TNBS) was used to induce chronic colitis. The level of inflammation was assessed macroscopically and histologically. In Ussing chamber experiments, colonic specimens from TNBS-treated animals exhibited a higher tissue conductance, that is, a higher epithelial permeability, and a slightly reduced basal short-circuit current (a measure of net ion transport) in relation to non-inflamed control tissue. Analgetic treatment with flupirtine, a central antinociceptive analgetic, did not interfere with the induction of the inflammatory response so that all animals were treated with flupirtine to reduce pain and distress during the development of colitis. The secretory response evoked by an exogenous H(2) S donor, NaHS, was significantly decreased after induction of colitis, whereas the response to Ca(2+) - or cAMP-dependent secretagogues was unaltered. This downregulation was not observed in the colitis group fed on a S-reduced diet. The decreased NaHS response indicates a desensitization of the tissue by inflammation, which might be explained by an upregulation of colonic H(2) S production as described in some models of inflammation. PMID:22963333

  19. Effect of cyclosporine in a murine model of experimental colitis.

    PubMed

    Banić, Marko; Anić, Branimir; Brkić, Tomislav; Ljubicić, Neven; Plesko, Sanja; Dohoczky, Csaba; Erceg, Damir; Petrovecki, Mladen; Stipancić, Igor; Rotkvić, Ivo

    2002-06-01

    The use of immunosuppressive therapy may be associated with significant toxicity. The aim of this study was to investigate the effect of cyclosporine A (CsA) in murine model of experimental colitis. Experimental colitis was induced in NMRI mice using an enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. After inducing colitis, experimental groups of animals were treated with CsA (1, 3, 5, 10, 25, 50 mg/kg/day) intraperitoneally (i.p.) or intracolonically (i.c.), and control groups were treated with phosphate-buffered saline intraperitoneally or intracolonically, respectively. Colonic inflammatory changes were assessed using a histopathologic score of 0-30, and pooled whole blood samples were processed with monoclonal antibodies for cyclosporine concentration. In addition, two groups of animals with experimental colitis were treated intraperitoneally or intracolonically with 3 mg/kg/day of CsA, and the colons were also taken for immunohistochemistry for CD25. CsA diminished the extent of colitis in groups treated with 3, 5, 10, or 25 mg/kg intraperitoneally or intracolonically, and in groups treated with 1 and 50 mg/kg intracolonically (P < 0.05). The effect of intracolonic application of CsA was not related to whole blood cyclosporine concentrations. In addition, the effect of CsA at 3 mg/kg, applied intraperitoneally or intracolonically was, in part, expressed in decreasing the numbers of CD25+ cells within colonic mucosa/submucosa (P < 0.05). In conclusions, the results of this study indicate the possibility of intracolonic application of cyclosporine in order to widen the therapeutic window for effective, but possibly toxic drug, such as cyclosporine. PMID:12064814

  20. 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

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

    PubMed

    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. PMID:27166517

  2. PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner

    PubMed Central

    Wei, Fanhua; Zhang, Yuying; Jian, Jinlong; Mundra, Jyoti Joshi; Tian, Qingyun; Lin, Jiqiang; Lafaille, Juan Jose; Tang, Wei; Zhao, Weiming; Yu, Xiuping; Liu, Chuan-Ju

    2014-01-01

    This study was aimed to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium (DSS)−, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and CD4+CD45Rbhi T cell transfer colitis model were established and analyzed in wild-type and several genetically-modified mice, including PGRN, IL-10 and TNFR2 deficient mice. Elevated levels of PGRN were found in colitis samples from human IBD patients and mouse colitis models in comparison to the corresponding controls. PGRN-deficient mice became highly susceptible to DSS- and TNBS-induced colitis, whereas recombinant PGRN ameliorated the pathology and reduced the histological score in both DSS and TNBS colitis models. In addition, hematopoietic-derived PGRN was critical for protection against DSS-induced colitis, and lack of PGRN signaling in CD4+ T cells also exacerbated experimental colitis. PGRN-mediated protective effect in colitis was compromised in the absence of IL-10 signaling. In addition, PGRN's effect was also largely lost in the TNFR2-deficient colitis model. Collectively, these findings not only provide the new insight into PGRN's anti-inflammatory action in vivo, but may also present PGRN and its derivatives as novel biological agent for treating IBD. PMID:25387791

  3. 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. PMID:22885429

  4. 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

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

    PubMed

    Imanzade, Farid; Sayarri, Aliakbar; Tajik, Pantea

    2015-01-01

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

  6. Pulmonary embolism in an immunocompetent patient with acute cytomegalovirus colitis

    PubMed Central

    Chou, Jen-Wei

    2016-01-01

    Acute cytomegalovirus (CMV) infection occurs commonly in immunocompromised and immunocompetent patients, but is usually asymptomatic in the latter. Vascular events associated with acute CMV infection have been described, but are rare. Hence, such events are rarely reported in the literature. We report a case of pulmonary embolism secondary to acute CMV colitis in an immunocompetent 78-year-old man. The patient presented with fever and diarrhea. Colonic ulcers were diagnosed based on colonoscopy findings, and CMV was the proven etiology on pathological examination. The patient subsequently experienced acute respiratory failure. Pulmonary embolism was diagnosed based on the chest radiography and computed tomography findings. A diagnosis of acute CMV colitis complicated by pulmonary embolism was made. The patient was successfully treated with intravenous administration of unfractionated heparin and intravenous ganciclovir. PMID:27175121

  7. A Case of Cerebral Vasculitis Associated with Ulcerative Colitis

    PubMed Central

    Raj, Naveen; Arkebauer, Matthew; Waters, Barry; Dickinson, Brucha

    2015-01-01

    Ulcerative colitis (UC) is a chronic, debilitating condition characterized by inflammation of the colonic mucosa. It is regarded as a systemic inflammatory disorder that can affect a number of organ systems. Central nervous system disease associated with UC is a rare sequela of inflammatory bowel disease, occurring in less than 5% of cases. These manifestations include arterial and venous thrombosis, leukoencephalitis, seizures, and vasculitis. We present a case of a 61-year-old female with a two-year history of well-controlled ulcerative colitis, who developed altered mental status and weakness. On brain imaging, she was found to have cerebral lesions which were biopsied. Histopathology subsequently revealed coagulative necrosis and inflammation characteristic of vasculitis. Rheumatology serologies were negative, and the patient was started on steroids that dramatically improved her neurological function, with no residual deficits, and led to resolution of the brain lesions. PMID:26557402

  8. [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

  9. Acute Myocardial Infarction Complicating Active Ulcerative Colitis: A Case Report

    PubMed Central

    Papadimitraki, Eva D.; Ahamed, Mubarak; Bunce, Nicholas H.

    2011-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease that predominantly affects the gastrointestinal (GI) tract but can involve extraintestinal organs including musculoskeletal system and skin. The most frequent cardiac manifestations of UC are pericarditis and myocarditis. Patients display an increased risk for venous thromboembolic complications and mesenteric ischemia, but the association with ischemic heart disease and myocardial infarction is uncertain. We present the case of a 27-year-old man with anti-PRIII ANCA-positive ulcerative colitis and increased factor VIII activity who presented with an acute myocardial infarction. We discuss possible causative links between these clinical entities and demonstrate the role of cardiac magnetic resonance (CMR) in patients with underlying inflammatory conditions who present with chest pain and evidence of myocardial damage. PMID:24826231

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

    PubMed

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

    2011-06-01

    Infliximab is a chimerical monoclonal antibody that inhibits pro-inflammatory activity of tumour-necrosis factor alpha (TNFα) and it is the primary biological agent used in the treatment of moderate-to-severe ulcerative colitis (UC). We report a case of vitiligo following infliximab administration in a patient with refractory UC. The case serves as a reminder of adverse cutaneous reactions induced by TNFα-antagonist therapy. PMID:21684486

  11. Inflammatory cells’ role in acetic acid-induced colitis

    PubMed Central

    Sanei, Mohammad H.; Hadizadeh, Fatemeh; Adibi, Peyman; Alavi, Sayyed Ali

    2014-01-01

    Background: Free radicals are the known mechanisms responsible for inducing colitis with two origins: Inflammatory cells and tissues. Only the inflammatory cells can be controlled by corticosteroids. Our aim was to assess the importance of neutrophils as one of the inflammatory cells in inducing colitis and to evaluate the efficacy of corticosteroids in the treatment of inflammatory bowel disease (IBD). Materials and Methods: Thirty-six mice were divided into six groups of six mice each. Colitis was induced in three groups by exposing them to acetic acid through enema (group 1), ex vivo (group 3), and enema after immune suppression (group 5). Each group had one control group that was exposed to water injection instead of acetic acid. Tissue samples were evaluated and compared based on macroscopic damages and biochemical and pathological results. Results: Considering neutrophilic infiltration, there were significant differences between groups 1, 3, 5, and the control of group 1. Groups 3, 5, and their controls, and group 1 and the control of group 3 had significant differences in terms of goblet depletion. Based on tissue originated H2O2, we found significant differences between group 1 and its control and group 3, and also between groups 5 and the control of group 3. All the three groups were significantly different from their controls based on Ferric Reducing Ability of Plasma (FRAP) and such differences were also seen between group 1 with two other groups. Conclusion: Neutrophils may not be the only cause of oxidation process in colitis, and also makes the effectiveness of corticosteroids in the treatment of this disease doubtful. PMID:25337523

  12. Antioxidants as novel therapy in a murine model of colitis.

    PubMed

    Oz, Helieh S; Chen, Theresa S; McClain, Craig J; de Villiers, Willem J S

    2005-05-01

    Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD) and have been implicated as mediators of intestinal inflammation. We investigated the hypothesis that antioxidants with diverse properties attenuate disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model. These antioxidants were (A) S-adenosylmethionine, a glutathione (GSH) precursor; (B) green tea polyphenols, a well-known antioxidant; and (C) 2(R,S)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA), a cysteine prodrug, involved in GSH biosynthesis. BALB/c mice were divided into four groups and provided with the above mentioned antioxidants or the vehicle incorporated into chow. The animals were further divided into two subgroups and given normal drinking water (control) or water supplemented with DSS (to induce colitis), and the progression of the disease was studied. DSS-treated mice developed severe colitis as shown by bloody diarrhea, weight loss and pathological involvement (P<.001). However, all the antioxidants significantly improved diarrhea and colon lesions (P<.01), and increased body weights (P<.05). Hematocrits were significantly less affected in DSS-treated animals receiving antioxidants (P<.01). Colon lengths were significantly decreased due to mucosal inflammation in DSS-treated animals, but antioxidant therapy normalized this pathological finding (P<.001). The blood level of reduced GSH was decreased in DSS-treated mice (P<.05) and returned to normal when treated with antioxidants. Serum amyloid A (acute phase protein; P=.0015) and tumor necrosis factor-alpha (TNF-alpha; pro-inflammatory cytokine; P<.01) were significantly increased in DSS-treated animals (161+/-40 pg/ml) and improved with antioxidant treatment (P<.01). Finally, actin cytoskeleton was distorted and fragmented in the mucosa of DSS-treated mice and improved with antioxidant therapy. In conclusion, three structurally dissimilar antioxidants provided protection against DSS

  13. 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

  14. Perioperative Considerations in Crohn Disease and Ulcerative Colitis.

    PubMed

    Nickerson, T Paul; Merchea, Amit

    2016-06-01

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

  15. A budesonide prodrug accelerates treatment of colitis in rats.

    PubMed Central

    Cui, N; Friend, D R; Fedorak, R N

    1994-01-01

    Although oral glucocorticoids are the treatment of choice for moderate to severe ulcerative pancolitis, their systemic side effects and adrenal suppression account for considerable morbidity. An oral glucocorticoid-conjugate (prodrug), budesonide-beta-D-glucuronide, which is not absorbed in the small intestine but is hydrolysed by colonic bacterial and mucosal beta-glucuronidase to release free budesonide into the colon was synthesised. The objective of this study was to compare treatment with budesonide-beta-D-glucuronide with treatment with free budesonide by examining: (1) the healing of experimental colitis and (2) the extent of adrenal suppression. Pancolitis was induced with 4% acetic acid. Animals were then randomised to receive oral therapy for 72 hours with (1) budesonide-beta-D-glucuronide, (2) free budesonide, or (3) vehicle. Drug efficacy and colitic healing was determined by measuring gross colonic ulceration, myeloperoxidase activity, and in vivo colonic fluid absorption. Adrenal suppression was determined by measuring plasma adrenocorticotrophic hormone and serum corticosterone. Vehicle-treated colitis animals had gross ulceration, increased myeloperoxidase activity, and net colonic fluid secretion. Treatment with oral budesonide-beta-D-glucuronide accelerated all measures of colitis healing at a fourfold lower dose than did free budesonide. Furthermore, treatment with budesonide-beta-D-glucuronide did not result in adrenal suppression whereas free budesonide treatment did. A newly synthesised orally administered glucocorticoid-conjugate accelerates colitis healing with limited adrenal suppression. Development of an orally administered colon-specific steroid delivery system represents a novel approach to inflammatory bowel disease treatment. PMID:7959202

  16. 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

  17. 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

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

    PubMed

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

    2015-07-15

    Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation. PMID:26021808

  19. Pseudomembranous colitis: an unusual cause of neutrocytic ascites.

    PubMed

    Spahr, L; de Saussure, P; Felley, C; Pugin, J; Hadengue, A

    1999-07-01

    Severe cases of pseudomembranous colitis (PMC) may be associated with intraperitoneal fluid accumulation. However, the characteristics of the liquid are seldom described. Specifically, neutrocytic ascites has only been reported once. We report a case of a severe PMC complicated by a highly neutrocytic ascites which remained culture-negative. We discuss the possible mechanisms leading to ascites formation in this condition and review ascitic fluid characteristics in patients with PMC. PMID:10445802

  20. 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

  1. 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

  2. Opposing roles of prostaglandin D2 receptors in ulcerative colitis.

    PubMed

    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

    2014-07-15

    Proresolution functions were reported for PGD2 in colitis, but the role of its two receptors, D-type prostanoid (DP) and, in particular, chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), is 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 dextran sulfate sodium 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 with 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-dehydro TXB2 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, whereas 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 most likely promotes anti-inflammatory actions. PMID:24929001

  3. 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

  4. Ulcerative colitis and antineutrophil cytoplasmic antibodies in Hong Kong Chinese.

    PubMed

    Sung, J Y; Chan, K L; Hsu, R; Liew, C T; Lawton, J W

    1993-06-01

    Inflammatory bowel diseases are known to be rare among the Chinese. The diagnosis of ulcerative colitis has been difficult in some of the Asian countries where infective colitis is more prevalent. Twenty-three Hong Kong Chinese patients diagnosed to have ulcerative colitis were reviewed. The symptoms were relatively mild and extraintestinal manifestation had been rare. Patients responded well to steroid therapy and sulfasalazine. Three patients in this series were found to have cyst and/or trophozoites of Entamoeba histolytica in stool. In this series, 19 patients were tested for antineutrophil cytoplasmic antibody (ANCA). Fourteen patients (73.5%) were positive, of which six (31.5%) showed a perinuclear staining pattern and eight (42%) demonstrated a cytoplasmic pattern. Five patients (26.5%) were negative for any ANCA, and none was positive for both. Sera of these patients were also tested for anti-alpha granules, anti-myeloperoxidase, and anti-lactoferrin activities. None was positive. Control sera collected from 16 patients with irritable bowel syndrome were all negative for the tests. In conclusion, testing of ANCAs may help in making the diagnosis of idiopathic inflammatory bowel disease in difficult situations. PMID:8503382

  5. Octreotide effectively decreases mucosal damage in experimental colitis.

    PubMed Central

    Eliakim, R; Karmeli, F; Okon, E; Rachmilewitz, D

    1993-01-01

    The effect of octreotide, a synthetic analogue of somatostatin, on the modulation of the acetic acid model of experimental colitis was examined. Colitis was induced by intracolonic administration of 2 ml of 5% acetic acid. The inflammatory response elicited by the acetic acid resulted in increased colonic synthesis of platelet activating factor, leukotriene B4 and decreased mucosal somatostatin levels. Subcutaneous administration of octreotide (10 micrograms/rat) 1 hour before or immediately after damage induction, as well as 1 and 23 hours after acetic acid application, resulted in a significant reduction in mucosal damage. The protective effect was accompanied by a significant reduction in platelet activating factor activity, leukotriene B4, and vasoactive intestinal peptide concentrations. There were no significant changes in mucosal leukotriene C4 and calcitonin gene related peptide levels. This study shows that acetic acid induced colitis is pharmacologically manipulated by octreotide. The mechanism of action of octreotide has not yet been fully determined. The potential use of octreotide in treating active inflammatory bowel disease remains to be evaluated. Images Figure 5 PMID:8381760

  6. [Management of diagnosis and treatment in ulcerative colitis].

    PubMed

    Klotz, Caroline; Barret, Maximilien; Dhooge, Marion; Oudjit, Ammar; Chaussade, Stanislas; Coriat, Romain; Abitbol, Vered

    2015-02-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease limited to the mucosa and affecting the rectum and the colon continuously. Salicylates are the first line treatment for moderate forms. Corticosteroids are used to induce remission, but are not given as maintenance therapy. Thiopurines are indicated as maintenance therapy in case of failure of salicylates or cortico-dependence. Anti TNF alpha are indicated in cortico-resistant severe flares or if cortico- dependence. Vedolizumab (anti-integrin) is the first non anti-TNF alpha biotherapy available for the treatment of UC. Severe acute colitis is a medical emergency; diagnosis is based on Lichtiger score. An emergency colectomy for severe acute colitis is indicated in cases of surgical complication or resistance to medical therapy. UC patients with extension beyond splenic flexure are at risk of colorectal cancer, increasing with the duration of the disease, severity of mucosal inflammation, family history of colorectal cancer, and the existence of sclerosing cholangitis. Annual surveillance colonoscopy is required in patients with sclerosing cholangitis regardless of the extension of their UC. PMID:25534469

  7. 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

  8. Escherichia coli 0157 enterohaemorrhagic colitis associated with pyelonephritis: CT findings.

    PubMed

    Heffernan, E; Chatur, N; Zwirewich, C

    2009-04-01

    Escherichia coli 0157:H7 is increasingly being recognized as a cause of infectious colitis, which typically results in bloody diarrhoea in an afebrile patient. The absence of fever often means that an infectious process is not considered in the differential diagnosis, particularly as this organism will not be detected in routine stool cultures. Inappropriate antibiotic therapy may increase the risk of development of haemolytic uraemic syndrome, a potentially fatal complication of this form of colitis, hence the importance of accurate diagnosis. On CT, it is characterized by severe diffuse colonic wall thickening, with little or no pericolic inflammatory changes. The radiologist may be the first to suspect the correct diagnosis and so should be aware of its imaging appearances. We report the case of a 19-year-old man who presented with typical radiological findings of enterohaemorrhagic colitis and whose CT also showed evidence of acute pyelonephritis; we suggest that this combination of abnormalities should further heighten radiologists' suspicions of infection due to E. coli 0157:H7, despite the absence of fever. PMID:19325040

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

    PubMed

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

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ) is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE) at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN- γ , IL-1 β , IL-6, IL-10, IL-12 (P40), IL-12 (P70), IL-17, and TNF- α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1 β and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1 β , IL-6, and IL-12 (P40) but not IFN- γ , IL-10, and IL-12 (P70). In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics. PMID:24948848

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

    PubMed

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

    2015-12-25

    Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfate sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. PMID:26603936

  11. β-Arrestin-1 deficiency protects mice from experimental colitis.

    PubMed

    Lee, Taehyung; Lee, Eunhee; Irwin, Regina; Lucas, Peter C; McCabe, Laura R; Parameswaran, Narayanan

    2013-04-01

    β-Arrestins are intracellular scaffolding proteins that modulate specific cell signaling pathways. Recent studies, in both cell culture and in vivo models, have demonstrated an important role for β-arrestin-1 in inflammation. However, the role of β-arrestin-1 in the pathogenesis of inflammatory bowel disease (IBD) is not known. Our goal was to investigate the role of β-arrestin-1 in IBD using mouse models of colitis. To this end, we subjected wild-type (WT) and β-arrestin-1 knockout (β-arr-1(-/-)) mice to colitis induced by trinitrobenzenesulfonic acid or dextran sulfate sodium and examined the clinical signs, gross pathology, and histopathology of the colon, as well as inflammatory components. The β-arr-1(-/-) mice displayed significantly attenuated colitis, compared with WT mice, in both models. Consistent with the phenotypic observations, histological examination of the colon revealed attenuated disease pathology in the β-arr-1(-/-) mice. Our results further demonstrate that β-arr-1(-/-) mice are deficient in IL-6 expression in the colon, but have higher expression of the anti-inflammatory IL-10 family of cytokines. Our results also demonstrate diminished ERK and NFκB pathways in the colons of β-arr-1(-/-) mice, compared with WT mice. Taken together, our results demonstrate that decreased IL-6 production and enhanced IL-10 and IL-22 production in β-arrestin-1-deficient mice likely lead to attenuated gut inflammation. PMID:23395087

  12. What's the Clinical Features of Colitis in Elderly People in Long-Term Care Facilities?

    PubMed Central

    Yoon, So Yoon; Na, Sun-Kyung; Ryu, Jae-In; Yun, Hye-Won; Lee, Min-Jin; Song, Eun-Mi; Kim, Seong-Eun; Jung, Hye-Kyung; Shim, Ki-Nam

    2015-01-01

    Background/Aims As life expectancy has increased, the number of elderly patients who need long-term care has grown rapidly. Mortality in patients with colitis in long-term care facilities (LTCFs) is increasing. We intend to investigate the main causes of colitis in LTCFs compared to those of colitis in local communities, and to identify the clinical features and risk factors of patients with colitis in LTCFs. Methods We retrospectively analyzed epidemiology, medical conditions, laboratory values, diagnoses, and clinical courses of elderly patients aged ≥65 who were admitted to the Ewha Womans University hospital with colitis between January 2007 and July 2012. Results Patients with colitis in LTCFs (n=20) were compared with elderly patients with colitis in local communities (n=154). Fifty-five percent of colitis in LTCFs was caused by Clostridium difficile infection (CDI), 30% was due to ischemic colitis, and 15% was due to non-specific colitis. Non-specific colitis was the most common (63%) in the community group. Clinical outcomes were also significantly different between both groups: higher mortality (10.0% vs. 0.64%, P=0.021), higher requirement for intensive care units care (50.0% vs. 18.8%, P<0.01) in LTCFs group. In univariate analysis, the most significant risk factor for death in patients in LTCFs was decreased mental faculties. Conclusions Patients in LTCFs showed worse clinical outcomes and a much higher prevalence of CDI compared to patients from local communities. We suggest early and active evaluation, such as endoscopic examination, for differential diagnosis in patients in LTCFs. PMID:25931997

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

    Maeda, Shin . E-mail: shinmaeda2-gi@umin.ac.jp; Hikiba, Yohko; Shibata, Wataru; Ohmae, Tomoya; Yanai, Ayako; Ogura, Keiji; Yamada, Shingo; Omata, Masao

    2007-08-24

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

  15. Herpes simplex colitis in a child with combined liver and small bowel transplant.

    PubMed

    Delis, S; Kato, T; Ruiz, P; Mittal, N; Babinski, L; Tzakis, A

    2001-10-01

    Herpes simplex virus (HSV) has been a rare cause of gastrointestinal (GI) infection, especially in immunocompromised patients. A variety of GI sites may be involved; however, only three reported cases of HSV colitis have been documented in the literature. To our knowledge, this is the first report of HSV colitis in a small bowel transplant recipient. PMID:11560759

  16. IL-17/IFN-γ interactions regulate intestinal inflammation in TNBS-induced acute colitis.

    PubMed

    Jin, Yu; Lin, Yan; Lin, Lianjie; Zheng, Changqing

    2012-11-01

    Colonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced acute colitis in mice and elicited a Th1 immune response. Th17 cells are believed to play a major role in TNBS-induced colitis. The aim of this study is to investigate the roles of interleukin (IL)-17 and interferon (IFN)-γ in the pathogenesis of TNBS-induced acute colitis. We assessed the inflammation scores of TNBS-induced acute colitis in wild-type (WT), IL-17 knockout (KO), and IFN-γ KO mice and measured the levels of inflammatory cytokines using real-time PCR and ELISAs. Histology data showed that IL-17 KO mice with TNBS-induced colitis had significantly lower neutrophil infiltration and inflammatory macroscopic scores compared to the IFN-γ KO mice and WT mice. Intraperitoneal injection of anti-IL-17 monoclonal antibody confirmed a specific role for IL-17 in TNBS-induced acute colitis in the 3 strains of mice. The severity of colitis was higher in IFN-γ KO mice and lower in IL-17 KO mice compared to WT mice. Our data suggested that IL-17 signaling plays a critical role in the local inflammation of TNBS-induced colitis, while IFN-γ was not an important mediator of the local inflammation response. IL-17 may represent a target for therapeutic intervention in inflammatory bowel disease patients. PMID:23030668

  17. Systemic lupus erythematosus in association with ulcerative colitis: related autoimmune diseases.

    PubMed

    Stevens, H P; Ostlere, L S; Rustin, M H

    1994-03-01

    We report a patient who developed urticaria, angio-oedema and polyarthropathy secondary to the hypocomplementaemic urticarial vasculitis syndrome, a year prior to the onset of ulcerative colitis. Ten years later, primary sclerosing cholangitis and the antiphospholipid syndrome developed concomitantly. We believe this patient represents only the second reported case of idiopathic systemic lupus erythematosus (SLE) occurring in association with ulcerative colitis. PMID:8148283

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

    PubMed Central

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

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa. PMID:26798415

  19. A precordial rub in a boy with a severe attack of ulcerative colitis.

    PubMed

    Badina, Laura; Ferrara, Giovanna; Guastalla, Pierpaolo; Barbi, Egidio

    2014-04-01

    A case of a pneumomediastinum mimicking a pericarditis in a boy with an occult perforation due to ulcerative colitis is reported. Pneumomediastinum is a rare complication of severe attacks of ulcerative colitis, with or without the previous development of a toxic megacolon, that should be considered in the differential diagnosis. PMID:24694884

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

    PubMed Central

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

    2015-01-01

    AIM: To determine the incidence and risk factors for colorectal cancer (CRC) in patients with ulcerative colitis from a low prevalence region for CRC. METHODS: Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men (57.7%)] with ulcerative colitis (median disease duration 6, range: 1-39 years) for analysis. Of these, 131 (30.5%) had left-sided colitis and 159 (37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of CRC. RESULTS: Twelve patients (2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease - 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained significant. CONCLUSION: CRC occurred in 2.8% of patients with ulcerative colitis in our population - an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our population. The risk increased with extent and duration of disease. PMID:25834332

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

    PubMed

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

    2016-01-01

    Malva sylvestris is an edible plant that is consumed as a herbal supplement for its antiulcer and colon cleansing properties in traditional Persian medicine. This study was designed to evaluate its effects on ulcerative colitis, which is a chronic gastrointestinal inflammation. Colitis was induced by rectal instillation of acetic acid solution. Rats in different groups received aqueous, n-hexane, or ethanolic fractions of the plant before induction of colitis. Isolated polysaccharide of plant was also tested in 2 groups before and after induction of colitis. Macroscopic and microscopic evaluation of colitis showed that the aqueous fraction was very effective in preventing the inflammation and efficacy was lower for ethanolic and n-hexane fractions. Polysaccharide was effective in reducing signs of inflammation, especially as pretreatment. These beneficial effects provide evidences that this plant can be suggested for patients with this disease to improve their health condition or to reduce adverse effects of their medication. PMID:26045553

  2. Relationship between Mast Cells and the Colitis with Relapse Induced by Trinitrobenzesulphonic Acid in Wistar Rats

    PubMed Central

    Luchini, Ana Carolina; Costa de Oliveira, Déborah Mara; Pellizzon, Cláudia Helena; Di Stasi, Luiz Claudio; Gomes, José Carlos

    2009-01-01

    The present study aimed to clarify the role of mast cells in colitis with relapse induced in Wistar rats by trinitrobenzenosulphonic acid. Colitis induction increased the histamine concentration in the colon, which peaked on day 26. The number of mast cells, probably immature, was ten times higher on day 8. Different from animals infected with intestinal parasites, after colitis remission, mast cells do not migrate to the spleen, showing that mast cell proliferation presents different characteristics depending on the inflammation stimuli. Treatment with sulfasalazine, doxantrazole, quercetin, or nedocromil did not increase the histamine concentration or the mast cell number in the colon on day 26, thereby showing absence of degranulation of these cells. In conclusion, although mast cell proliferation is associated with colitis, these cells and their mediators appear to play no clear role in the colitis with relapses. PMID:19436763

  3. Successful treatment of ulcerative colitis with leukocytapheresis using non-woven polyester filter.

    PubMed

    Sakata, Hiromi; Kawamura, Naoyuki; Horie, Takashi; Ohizumi, Hiroko; Tamaki, Tohru; Kukita, Kazutaka; Meguro, Jun-ichi; Yonekawa, Motoki; Saitoh, Masao; Kawamura, Akio

    2003-12-01

    Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Although the pathogenesis of ulcerative colitis is not fully elucidated, cell-mediated immunity plays an important role in disease pathogenesis. Leukocytapheresis is a newly emerging therapy to eliminate activated leukocyte from systemic circulation. We have studied the effects of leukocytapheresis on patients with ulcerative colitis who had failed to respond to conventional therapy. A total of 51 patients with ulcerative colitis were treated with apheresis using a non-woven polyester fiber filter (Finecell, Asahi Medical Co.,Tokyo, Japan) originally developed as a microcoagulation elimination filter for massive transfusion. Of the 51 patients, 33 (64.7%) achieved clinical remission manifested by clinical activity and colonoscopic findings without any adverse effects. This result suggested that leukocytapheresis using Finecell might serve as an alternative therapy for ulcerative colitis as other leukocytapheresis using centrifugation or column. PMID:15018240

  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. PMID:27424097

  5. 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

  6. 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

  7. Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis

    PubMed Central

    Stremmel, W; Merle, U; Zahn, A; Autschbach, F; Hinz, U; Ehehalt, R

    2005-01-01

    Background and aims: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. Methods: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAI) of ⩾4. Retarded release phosphatidylcholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAI towards clinical remission (CAI ⩽3) or CAI improvement by ⩾50%. Secondary end points included ⩾50% changes in endoscopic activity index (EAI), histology, and quality of life scores. Results: Induction of clinical remission (CAI ⩽3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAI improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAI score (70% improvement) was recorded in the phosphatidylcholine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p = 0.00005). Conclusion: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis. PMID:15951544

  8. Crohn’s and colitis in children and adolescents

    PubMed Central

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

    2012-01-01

    Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications. PMID:23139601

  9. Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

    PubMed Central

    Matsuo, Shingo; Yang, Weng-Lang; Aziz, Monowar; Kameoka, Shingo; Wang, Ping

    2014-01-01

    Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or dimethyl sulfoxide (DMSO) (vehicle) was administered intraperitoneally from d 2 to 6. Clinical parameters were monitored daily. Mice were euthanized on d 8 for histological evaluation and measurements of colon length, chemokine, cytokine and inflammatory mediator expression. C75 significantly reduced body weight loss from 23% to 15% on d 8, compared with the vehicle group. The fecal bleeding, diarrhea and colon histological damage scores in the C75-treated group were significantly lower than scores in the vehicle animals. Colon shortening was significantly improved after C75 treatment. C75 protected colon tissues from DSS-induced apoptosis by inhibiting caspase-3 activity. Macrophage inflammatory protein 2, keratinocyte-derived chemokine, myeloperoxidase activity and proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β and IL-6) in the colon were significantly downregulated in the C75-treated group, compared with the vehicle group. Treatment with C75 in colitis mice inhibited the elevation of FASN, cyclooxygenase-2 and inducible nitric oxide synthase expression as well as IκB degradation in colon tissues. C75 administration alleviates the severity of colon damage and inhibits the activation of inflammatory pathways in DSS-induced colitis. Thus, inhibition of FASN may represent an attractive therapeutic potential for treating IBD. PMID:24306512

  10. 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

  11. Chronic eosinophilic pancreatitis and ulcerative colitis in a horse.

    PubMed

    Breider, M A; Kiely, R G; Edwards, J F

    1985-04-15

    A generalized debilitating disease in a horse was believed to be related to hypersensitivity to migrating strongyle larvae. The clinical signs included weight loss, diarrhea, and ulcers on all 4 coronary bands. The mare's condition deteriorated rapidly, so the mare was euthanatized and necropsied. The major histopathologic findings were chronic multifocal eosinophilic pancreatitis, hepatic portal fibrosis, biliary hyperplasia, and chronic ulcerative eosinophilic colitis. This case was similar to previously reported cases of chronic eosinophilic gastroenteritis in horses. Although the etiologic agent was not evident, the distribution and character of the lesions were consistent with a hypersensitivity response to migrating parasitic larvae, most probably Strongylus equinus. PMID:3997643

  12. Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

    PubMed

    Rumessen, J J; Vanderwinden, J-M; Horn, T

    2010-10-01

    Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC. PMID:20568987

  13. 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

  14. Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation.

    PubMed

    Melgar, Silvia; Karlsson, Agneta; Michaëlsson, Erik

    2005-06-01

    Exposure to dextran sulfate sodium (DSS) induces acute colitis, which is normally resolved after DSS removal. To study chronicity, mice are typically subjected to three to five cycles of weekly DSS exposures, each followed by a 1- to 2-wk rest period. Here, we describe a novel and convenient way of inducing chronic, progressive colitis by a single exposure to DSS. C57BL/6 mice exposed to DSS for 5 days developed acute colitis that progressed to severe chronic inflammation. The plasma haptoglobin levels remained high during the chronic phase, showing that the inflammation was active. Surprisingly, the mice regained their original weight along with the progression of colitis, and the only apparent symptom was loose feces. Histopathological changes 4 wk after DSS removal were dense infiltrates of mononuclear cells, irregular epithelial structure, and persistent deposits of collagen. A progressive production of the cytokines IL-1beta, IL-12 p70, and IL-17 correlated with the extensive cellular infiltration, whereas high IFN-gamma production was mainly found late in the chronic phase. Similar to C57BL/6 mice, BALB/c mice exposed to 5 days of DSS developed acute colitis as previously described. The acute colitis was accompanied by elevated plasma levels of haptoglobin and increased colonic levels of IL-1alpha/beta, IL-6, IL-18, and granulocyte colony-stimulating factor. However, soon after DSS removal, BALB/c mice recovered and were symptom free within 2 wk and completely recovered 4 wk after DSS removal in terms of histopathology, haptoglobin levels, and local cytokine production. In summary, these data stress the effect of genetic background on the outcome of DSS provocation. We believe that the present protocol to induce chronic colitis in C57BL/6 mice offers a robust model for validating future therapies for treatment of inflammatory bowel disease. PMID:15637179

  15. 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

  16. Ulcerative colitis with inflammatory polyposis in a teenage boy: A case report

    PubMed Central

    Feng, Jin-Shan; Ye, Ying; Guo, Can-Can; Luo, Bo-Tao; Zheng, Xue-Bao

    2015-01-01

    Ulcerative colitis in addition to inflammatory polyposis is common. The benign sequel of ulcerative colitis can sometimes mimic colorectal carcinoma. This report describes a rare case of inflammatory polyposis with hundreds of inflammatory polyps in ulcerative colitis which was not easy to distinguish from other polyposis syndromes. A 16-year-old Chinese male suffering from ulcerative colitis for 6 mo underwent colonoscopy, and hundreds of polyps were observed in the sigmoid, causing colonic stenosis. The polyps were restricted to the sigmoid. Although rectal inflammation was detected, no polyps were found in the rectum. A diagnosis of inflammatory polyposis and ulcerative colitis was made. The patient underwent total colectomy and ileal pouch anal anastomosis. The patient recovered well and was discharged on postoperative day 8. Endoscopic surveillance after surgery is crucial as ulcerative colitis with polyposis is a risk factor for colorectal cancer. Recognition of polyposis requires clinical, endoscopic and histopathologic correlation, and helps with chemoprophylaxis of colorectal cancer, as the drugs used postoperatively for colorectal cancer, ulcerative colitis and polyposis are different. PMID:25624746

  17. Anti-inflammatory effect of elemental diets with different fat composition in experimental colitis.

    PubMed

    Papada, E; Kaliora, A C; Gioxari, A; Papalois, A; Forbes, A

    2014-04-14

    The aim of the present study was to evaluate the effectiveness of two isoenergetic elemental formulae with different fat content in the rat model of trinitrobenzene sulphonic acid (TNBS) colitis that mimics human inflammatory bowel disease. A total of forty-five male Wistar rats were assigned to five groups: (1) control group; (2) TNBS-induced colitis group; (3) TNBS-induced colitis group fed a long-chain TAG (LCT)-rich diet; (4) TNBS-induced colitis group fed a medium-chain TAG (MCT)-rich diet; (5) TNBS-induced colitis group fed a baseline diet and administered infliximab. Nutritional management lasted 12 d before and 4 d after rectal administration of TNBS. Subsequently, the rats were killed, and colonic tissue samples were collected for the assessment of histology, inflammation and oxidative stress. The MCT-rich diet decreased IL-6, IL-8 and intercellular adhesion molecule-1 (ICAM-1) levels and glutathione S-transferase (GST) activity, while the LCT-rich diet reduced only ICAM-1 levels and GST activity (P<0.05). Neither elemental formula affected IL-10 levels. Infliximab reduced IL-8 and ICAM-1 levels and GST activity and increased IL-10 levels (P<0.05). No significant differences were detected in oxidative stress. Histological damage scores differed significantly only between the control and the TNBS-induced colitis group. A MCT-rich formula seems to exert stronger anti-inflammatory effects than a LCT-rich formula in TNBS colitis. PMID:24229480

  18. Increased colonic apelin production in rodents with experimental colitis and in humans with IBD.

    PubMed

    Han, Song; Wang, Guiyun; Qiu, Suimin; de la Motte, Carol; Wang, Hui-Qun; Gomez, Guillermo; Englander, Ella W; Greeley, George H

    2007-08-16

    Apelin and its receptor, the APJ receptor, are expressed in the gastrointestinal tract. The aims of this study were to examine the effects of sodium dextran sulfate (DSS)-induced experimental colitis in rats and mice and inflammatory bowel disease (IBD) in humans on intestinal apelin production, and the influence of exogenous apelin on colonic epithelial cell proliferation in mice. In rodents with experimental colitis, colonic apelin mRNA levels were elevated during the inflammatory reaction as well as during the tissue repair phase that ensues after DSS withdrawal. Fluctuations in colonic apelin expression were paralleled by similar changes in apelin immunostaining. Apelin immunostaining was increased in the surface epithelium, in epithelial cells along the length of the tubular gland and in the stem cell region at the gland base. In ulcerative colitis (UC) and Crohn's disease patients, apelin immunostaining revealed a pattern of increased intestinal apelin content similar to that observed in rodents with experimental colitis. Administration of synthetic apelin to mice during the recovery phase of DSS-induced colitis stimulated colonic epithelial cell proliferation significantly. Our observations that colonic apelin production is increased during and after DSS exposure indicate that apelin plays multiple roles during the different stages of colitis. Additionally, the stimulatory action of exogenous apelin on colonic epithelial proliferation suggests that the increased apelin production during intestinal recovery stage may contribute to the repair of the intestinal epithelium in experimental rodent models of colitis and in IBD patients. PMID:17391779

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

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

    2015-01-01

    Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties. PMID:26713317

  20. Fecal calprotectin is a useful marker to diagnose ulcerative colitis from irritable bowel syndrome

    PubMed Central

    Kalantari, Hamid; Taheri, Akhtar; Yaran, Majid

    2015-01-01

    Background: This study was aimed to evaluate the predictive value of fecal calprotectin in patients with ulcerative colitis from patients with irritable bowel syndrome (IBS). Materials and Methods: Between May and October 2013, 88 adult patients, between the age 18 and 65 years with a history of chronic diarrhea of unknown origin were assessed. Standard colonoscopies were performed in all patients to assess ulcerative colitis. Before colonoscopies, they were asked to supply a stool specimen. Fecal calprotectin value was measured using a commercial enzyme-linked immunosorbent assay kit. Results: The mean of age, gender combination, and body mass index were not significantly different between patients with ulcerative colitis or IBS. The duration of disease in ulcerative colitis patients was significantly higher than IBS patients (P < 0.0001). The level of calprotectin in ulcerative colitis patients was significantly higher than IBS patients (265.9 vs 115.8, respectively, P = 0.001). Also, cutoff value >164 μg/g with sensitivity and specify of 57 (CI: 41%–71.6%), and 75 (CI: 59.7%–56.8%), respectively, was the best for discrimination between patients with ulcerative colitis and those with IBS. Conclusion: Our results show that fecal calprotectin as a noninvasive method, which can be used to identify patients with ulcerative colitis from IBS patients has low sensitivity and specificity. PMID:26015911

  1. 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

  2. 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

  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. 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

  5. Fulminant ulcerative colitis in a healthy pregnant woman

    PubMed Central

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

    2015-01-01

    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. Laparoscopic surgery for ulcerative colitis: a review of the literature.

    PubMed

    Hata, Keisuke; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Tanaka, Junichiro; Tanaka, Toshiaki; Nishikawa, Takeshi; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2015-08-01

    Despite the development of new therapies, including anti-TNF alpha antibodies and immunosuppressants, a substantial proportion of patients with ulcerative colitis (UC) still require surgery. Restorative proctocolectomy with ileal-pouch anal anastomosis is the standard surgical treatment of choice for UC. With the advent of laparoscopic techniques for colorectal surgery, ileal-pouch anal anastomosis has also been performed laparoscopically. This paper reviews the history and current trends in laparoscopic surgery for UC. The accumulation of experience and improvement of laparoscopic devices have shifted the paradigm of UC surgery towards laparoscopic surgery over the past decade. Although laparoscopic surgery requires a longer operation, it provides significantly better short and long-term outcomes. The short-term benefits of laparoscopic surgery over open surgery include shorter hospital stays and fasting times, as well as better cosmesis. The long-term benefits of laparoscopy include better fecundity in young females. Some surgeons favor laparoscopic surgery even for severe acute colitis. More efforts are being made to develop newer laparoscopic methods, such as reduced port surgery, including single incision laparoscopic surgery and robotic surgery. PMID:25346254

  7. 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

  8. 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

  9. Bax is downregulated in inflamed colonic mucosa of ulcerative colitis

    PubMed Central

    Iimura, M; Nakamura, T; Shinozaki, S; Iizuka, B; Inoue, Y; Suzuki, S; Hayashi, N

    2000-01-01

    BACKGROUND AND AIMS—One form of epithelial cell injury in inflamed colonic mucosa in ulcerative colitis (UC) is reported to involve apoptosis of these cells. Bcl-2 family proteins Bax and Bcl-2 are the major regulators of apoptosis. The aim of this study was to elucidate the involvement of the Bax/Bcl-2 system in induction of apoptosis of the inflamed colonic epithelium in UC.
METHODS—Colonic epithelium was isolated from colonic biopsy specimens. Expression of CD95, Bax, Bcl-xL, and Bcl-2 proteins was determined by western blotting. Bax gene expression was assessed by both reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern hybridisation and a real time PCR assay.
RESULTS—Equal levels of expression of CD95, Bcl-xL, and Bcl-2 proteins were noted in normal and UC colonic epithelia. Equal levels of expression of Bax protein and mRNA were noted in epithelia of normal colon and inactive UC. Levels of expression of Bax protein and mRNA were markedly reduced in inflamed UC colonic epithelium.
CONCLUSIONS—Our study showed for the first time downregulation of Bax in inflamed colonic epithelium of UC. The Bax/Bcl-2 system did not seem to be involved in induction of apoptosis of epithelial cells in the inflamed colonic mucosa of UC.


Keywords: ulcerative colitis; apoptosis; Bax; Bcl-2; Bcl-xL; CD95 PMID:10896914

  10. Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase

    PubMed Central

    Gao, Qiang; Esworthy, R. Steven; Kim, Byung-Wook; Synold, Timothy W.; Smith, David D.; Chu, Fong-Fong

    2010-01-01

    The pro-inflammatory effect of high-fat diet has been observed beyond the cardiovascular system, but there is little evidence to support its role in triggering inflammatory bowel disease. GPx1/2-double knockout (DKO) mice deficient in two intracellular glutathione peroxidases, GPx1 and GPx2, on a C57BL/6 (B6) background, have mild ileocolitis on a conventional chow. We fed B6 DKO mice two atherogenic diets to test the dietary effect on atherosclerosis and ileocolitis. Both atherogenic diets have high cholesterol, the Chol+/CA diet has cholic acid (CA) and the Chol+ diet has no CA. The Chol+/CA diet induced severe colitis, but not ileitis, in the DKO mice compared with Chol+ and a Chol- control diet. On the Chol+/CA diet, the wild-type (WT) mice had similar levels of aortic lesions and hypercholesterolemia as DKO mice did, but had no intestinal pathology. The diet-associated inflammatory responses in the DKO mice included increase of colonic pro-inflammatory serum amyloid A 3 expression, plasma lipopolysaccharide and TNF-α levels. The Chol+/CA diet has lowered the expression of unfolded protein response genes, ATF6, CHOP, unspliced XbpU and Grp78/Bip, in WT and DKO mice on the Chol- diet. Thus, we conclude that cholesterol diet weakens colon unfolded protein response, which can aggravate spontaneous colitis leading to gut barrier breakdown. GPx has no impact on atherosclerosis without ultra-hypercholesterolemia. PMID:20848490

  11. Achilles tendinitis as a rare extraintestinal manifestation of ulcerative colitis.

    PubMed

    Zenda, Takahiro; Araki, Ichiro; Nakamiya, Otoyuki; Tokuumi, Yuji; Shimada, Yuka; Komai, Keigo; Taniuchi, Yukie

    2016-06-01

    Patients with inflammatory bowel disease often have extraintestinal manifestations (EIMs) involving almost all organ systems, but little has been reported on Achilles tendinitis. Herein, we present a unique case of Achilles tendinitis, which manifested shortly after initiation of mesalazine therapy for ulcerative colitis. A 26-year-old Japanese woman with bloody diarrhea and abdominal cramps lasting for 7 days was referred to our hospital. The Lichtiger clinical activity index (CAI) score was 9 at the first visit. Based on the clinical symptoms and examination results, she was diagnosed with ulcerative pancolitis in the active phase, and treatment with mesalazine (2.4 g/day) and probiotics was initiated. Her symptoms resolved within 7 days of treatment (CAI 3). However, she then developed bilateral Achilles tendinitis without any apparent cause. The Achilles tendinitis subsided with conservative management within 2 weeks, despite continuation of mesalazine therapy. This case instructively suggests that Achilles tendinitis should be noted as an EIM of ulcerative colitis. PMID:27059338

  12. 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

  13. 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

  14. Peroxisome proliferator-activated receptor-γ is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia

    PubMed Central

    DOU, XIAOTAN; XIAO, JUNHUA; JIN, ZILIANG; ZHENG, PING

    2015-01-01

    The aim of the present study was to evaluate the expression of peroxisome proliferator-activated receptor (PPAR)-γ in inflammatory bowel disease (IBD), and to also identify the association between PPAR-γ and the clinical features of patients with IBD. An azoxymethane (AOM)/dextran sodium sulfate (DSS) animal model of colitis-associated neoplasia was established to investigate the protective effect of 5-aminosalicylic acid (5-ASA) and to explore the changes in the expression of PPAR-γ during this process. A total of 66 specimens of colorectal tissue obtained from biopsy performed on IBD patients and 30 healthy control individuals were immunohistochemically stained for PPAR-γ. An AOM/DSS animal model of colitis-associated neoplasia was then established. Reverse transcription quantitative polymerase chain reaction was conducted and it was found that, compared with the control group and patients with Crohn's disease (CD), the expression of PPAR-γ in the intestinal tissue of patients with ulcerative colitis (UC) was significantly decreased (P=0.027 and 0.046, respectively). The expression of PPAR-γ was found to be negatively associated with the disease activity of UC and was not associated with the severity of disease, site of lesions or CD characteristics. Administration of 5-ASA decreased the colitis and tumor burden of colons. The expression level of PPAR-γ in the intestinal tissue was also increased in the AOM/DSS/5-ASA group compared with AOM/DSS group (P<0.001). PPAR-γ is an important factor in the pathogenesis of UC and colitis-associated cancer. The present study found that 5-ASA significantly alleviates the colitis and tumor burden in a mouse model of AOM/DSS-induced colitis-associated neoplasia, and promotes the expression of PPAR-γ in the intestinal tract. PMID:26622660

  15. Combined Arterial and Venous Thrombosis in Ulcerative Colitis- A Rare Vascular Manifestation

    PubMed Central

    Singh, Harpreet; Dewan, Richa; Anuradha, S; Singla, Sumeet

    2016-01-01

    Combined arterial and venous thrombosis in patients with ulcerative colitis is a rare extra vascular manifestation, which motivated the current report. Increased coagulability is a recognised feature of ulcerative colitis with frequency increasing during flares. We report the case of a 42-year-old lady who was a diagnosed case of ulcerative colitis, currently in remission. She presented with swelling followed by discolouration of left lower limb which later was diagnosed as deep venous thrombosis combined with femoral and popliteal artery thrombosis. This led to wet gangrene of the limb, sepsis, septic shock and death despite aggressive management with heparin infusion, ionotropes, and parenteral antibiotics therapy. PMID:27190869

  16. Apparent change of Rhesus blood group typing in a case of ulcerative colitis.

    PubMed

    Tien, S L; Ong, Y W; Ng, H S

    1991-08-01

    An interesting case of ulcerative colitis with an apparent change of Rhesus blood group typing is described. To our knowledge, this has not been reported before. We postulate that during the initial active phase of ulcerative colitis, an unknown D-like antigen, possibly bacterial in origin, could temporarily give rise to a Rhesus D-positive blood group typing in a patient with Rhesus D-negative blood type. Interestingly, with continuous immunosuppressive therapy for ulcerative colitis, the patient did not develop anti-D antibodies despite multiple transfusions with D-positive blood. PMID:1776013

  17. Ispaghula husk may relieve gastrointestinal symptoms in ulcerative colitis in remission.

    PubMed

    Hallert, C; Kaldma, M; Petersson, B G

    1991-07-01

    The efficiency of ispaghula husk in relieving gastrointestinal symptoms in patients with ulcerative colitis in remission was studied in a placebo-controlled trial running for 4 months. Twenty-nine patients (81%) completed the trial; four withdrew after colitis relapse (three while receiving placebo). Grading of symptoms judged ispaghula to be consistently superior to placebo (p less than 0.001) and associated with a significantly higher rate of improvement (69%) than placebo (24%) (p less than 0.001). The results show that ispaghula can be helpful in the management of gastrointestinal symptoms in quiescent ulcerative colitis. PMID:1654592

  18. Unfractionated Heparin and New Heparin Analogues from Ascidians (Chordate-Tunicate) Ameliorate Colitis in Rats*

    PubMed Central

    Belmiro, Celso L. R.; Castelo-Branco, Morgana T. L.; Melim, Leandra M. C.; Schanaider, Alberto; Elia, Celeste; Madi, Kalil; Pavão, Mauro S. G.; de Souza, Heitor S. P.

    2009-01-01

    The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-α, TGF-β, and VEGF was observed, as well as a reduction of NF-κB and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin. PMID:19258310

  19. Enhanced Levels of Chemokines and Their Receptors in the Colon of Microscopic Colitis Patients Indicate Mixed Immune Cell Recruitment

    PubMed Central

    Günaltay, Sezin; Bohr, Johan; Hultgren, Olof

    2015-01-01

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX3CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX3CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses. PMID:25948880

  20. Treatment of ulcerative colitis in the cottontop tamarin using antibody to tumour necrosis factor alpha.

    PubMed Central

    Watkins, P E; Warren, B F; Stephens, S; Ward, P; Foulkes, R

    1997-01-01

    BACKGROUND: The aetiology and pathophysiology of ulcerative colitis remains unclear; however, there is increasing recognition of the critical role of inflammatory cytokines in the pathogenesis of this disease. Among these, tumour necrosis factor alpha (TNF alpha) seems to play an important role. AIM: To study the effects of an engineered human monoclonal antibody to TNF alpha (CDP571) in the treatment of idiopathic ulcerative colitis in the cottontop tamarin. METHODS: Six cottontop tamarins with confirmed ulcerative colitis received repeated doses of CDP571. Progression of disease was assessed by measuring both body weight and rectal biopsy pathology. RESULTS: All animals showed a rapid improvement in clinical condition and rectal biopsy pathology that was maintained following completion of the therapy. CONCLUSION: These studies indicate the efficacy of selective antibody therapy to TNF alpha for the treatment of ulcerative colitis in a primate and suggest that similar therapy in human could be of value. Images PMID:9203942

  1. Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

    PubMed Central

    Akcan, Alper; Kucuk, Can; Sozuer, Erdogan; Esel, Duygu; Akyildiz, Hizir; Akgun, Hulya; Muhtaroglu, Sabahattin; Aritas, Yucel

    2008-01-01

    AIM: To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerative colitis model. METHODS: Rats were randomly assigned to three groups: groupI: control, group II: experimental colitis, group III: colitis plus melatonin treatment. On d 11 after colitis, plasma tumor necrosis factor-α, portal blood endotoxin levels, colon tissue myeloperoxidase and caspase-3 activity were measured. Bacterial translocation was quantified by blood, lymph node, liver and spleen culture. RESULTS: We observed a significantly reduced incidence of bacterial translocation to the liver, spleen, mesenteric lymph nodes, portal and systemic blood in animals treated with melatonin. Treatment with melatonin significantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid- treated rats (16.11 ± 2.46 vs 32.97 ± 3.91, P < 0.01). CONCLUSION: Melatonin has a protective effect on bacterial translocation and apoptosis. PMID:18240350

  2. 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

  3. /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.

  4. 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

  5. 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. PMID:26690604

  6. The effect of Hypericum perforatum (St. John's Wort) on experimental colitis in rat.

    PubMed

    Dost, Turhan; Ozkayran, Hakan; Gokalp, Filiz; Yenisey, Cigdem; Birincioglu, Mustafa

    2009-06-01

    The aim of the present study was to investigate the effect of Hypericum perforatum (HP) on the inflammatory and immune response of colonic mucosa in rat with induced inflammatory bowel disease and that on various enzyme activities in blood and bowel tissue. Male Wistar albino rats were divided into three main groups: control, third day, and seventh day of colitis. Third-day and seventh-day groups were divided into four subgroups. Colitis was induced in all groups except the control group by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The colitis group received saline; treatment groups received HP extract (50, 150, and 300 mg/kg/day, respectively). Glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) activities in blood were measured. Catalase, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), glutathione reductase (GR), malondialdehyde, and nitric oxide (NO) activities were measured from tissue samples. Colonic damage was significantly reduced by HP extract. Macroscopic scoring of colonic damage significantly reduced in groups given HP extract compared with in the colitis group (P < 0.001). Blood catalase levels were reduced in the HP (150 mg/kg/day) compared with the colitis group (P < 0.01). Blood GSH levels significantly increased in groups treated with HP compared with control (P < 0.001) on the third and seventh day. Tissue GR levels reduced in the colitis and HP (50 mg/kg/day) groups compared with control (P < 0.05). Tissue MPO activity increased in the colitis and treatment groups compared with control (P < 0.007). GSH-Px levels increased in the colitis group compared with control at day 3 (P = 0.006). HP has a protective effect on TNBS-induced inflammatory bowel disease (IBD), probably due to an anti-inflammatory and antioxidant mechanism. PMID:18754092

  7. 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

  8. Successfully Treated Acute Fulminant Myocarditis Induced by Ulcerative Colitis with Extracorporeal Life Support and Infliximab

    PubMed Central

    Kim, Han-Kyul; Kim, Kun Il; Jung, Sung Won; Mun, Hee-Sun; Cho, Jung Rae; Lee, Namho

    2016-01-01

    We report a case of successfully treated acute fulminant myocarditis induced by ulcerative colitis with extracorporeal life support and infliximab. Myocarditis is a rare but crucial complication during an exacerbation of inflammatory bowel disease. In our case, we applied extracorporeal membrane oxygenation (ECMO) for cardiac rest under impression of acute myocarditis associated with ulcerative colitis, and added infliximab for uncontrolled inflammation by corticosteroid. As a result, our patient was completely recovered with successful weaning of ECMO. PMID:27358710

  9. Acute colitis produced by chemotactic peptides in rats and mice.

    PubMed Central

    Chester, J. F.; Ross, J. S.; Malt, R. A.; Weitzman, S. A.

    1985-01-01

    Colonic inflammation was produced in rats and mice by peptides chemotactic for polymorphonuclear leukocytes. Instillation of formylmethionyl-leucyl-phenylalanine (FMLP) and formylnorleucyl-leucyl-phenylalanine (FNLP) into isolated segments of rat colon caused marked mucosal edema and polymorphonuclear leukocyte infiltration within 2 hours. Higher concentrations of FNLP caused ulceration and necrosis as well. Formylmethionine (FMet), a compound with less chemotactic activity, caused much less inflammation. In mice, rectal instillation of FNLP caused dose-dependent acute mucosal inflammation which persisted for longer than 12 hours. Twice-weekly rectal instillation of FNLP provided a model of colitis based on neutrophil chemotaxis. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:4061566

  10. 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

  11. 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

  12. 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

  13. Liver transplantation in a patient with cholangiocarcinoma and ulcerative colitis.

    PubMed Central

    Abouna, G. M.; Preshaw, R. M.; Silva, J. L.; Hollingsworth, W. J.; Hershfield, N. B.; Novak, W.; Shaw, D. T.; Vetters, J. M.

    1976-01-01

    A 39 year-old patient with cholangiocarcinoma and pre-existing ulcerative colitis was successfully treated by orthotopic liver transplantation. He was given low doses of prednisone and azathioprine and survived for more than 9 months, dying with tumour metastases, thrombosis of the inferior vena cava and an intra-abdominal abscess. At autopsy the homograft showed little evidence of rejection. Preoperatively the patient had septicemia. Removal of his liver was difficult. The discrepancy between donor and recipient in size of blood vessels and the presence of two hepatic arteries in the donor caused problems during the vascular anastomoses. During the operation cardiac arrest occurred. Postoperatively there were several medical and surgical problems, including intraperitoneal and gastrointestinal hemorrhage, paralysis of the right dome of the diaphragm, sinus bradycardia, massive diuresis, peroneal nerve palsy, and one major and three minor episodes of rejection, which were reversed by giving pulse doses of methylprednisolone intravenously. Images FIG. 1 FIG. 2 FIG. 5 PMID:184908

  14. 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.

  15. 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

  16. Methyl deficient diet aggravates experimental colitis in rats.

    PubMed

    Chen, Min; Peyrin-Biroulet, Laurent; George, Amandine; Coste, Florence; Bressenot, Aude; Bossenmeyer-Pourie, Carine; Alberto, Jean-Marc; Xia, Bing; Namour, Bernard; Guéant, Jean-Louis

    2011-11-01

    Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n = 12-16 per group): C DSS(-) (control/DSS(-)), D DSS(-) (deficient/DSS(-)), C DSS(+) (control/DSS(+)) and D DSS(+) (deficient/DSS(+)). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS(+) group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS(+) pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients. PMID:21199330

  17. Vascular Microarchitecture of Murine Colitis-Associated Lymphoid Angiogenesis

    PubMed Central

    Turhan, Aslihan; Lin, Miao; Lee, Grace S.; Miele, Lino; Tsuda, Akira; Konerding, Moritz A.; Mentzer, Steven J.

    2010-01-01

    In permissive tissues, such as the gut and synovium, chronic inflammation can result in the ectopic development of anatomic structures that resemble lymph nodes. These inflammation-induced structures, termed lymphoid neogenesis or tertiary lymphoid organs, may reflect differential stromal responsiveness to the process of lymphoid neogenesis. To investigate the structural reorganization of the microcirculation involved in colonic lymphoid neogenesis, we studied a murine model of dextran sodium sulfate (DSS)-induced colitis. Standard 2-dimensional histology demonstrated both submucosal and intramucosal lymphoid structures in DSS-induced colitis. A spatial frequency analysis of serial histologic sections suggested that most intramucosal lymphoid aggregates developed de novo. Intravital microscopy of intravascular tracers confirmed that the developing intramucosal aggregates were supplied by capillaries arising from the quasi-polygonal mucosal plexus. Confocal optical sections and whole mount morphometry demonstrated capillary networks (185±46um diameter) involving 6–10 capillaries with a luminal diameter of 6.8±1.1um. Microdissection and angiogenesis PCR array analysis demonstrated enhanced expression of multiple angiogenic genes including CCL2, CXCL2, CXCL5, Il-1b, MMP9 and TNF within the mucosal plexus. Intravital microscopy of tracer particle flow velocities demonstrated a marked decrease in flow velocity from 808±901um/sec within the feeding mucosal plexus to 491±155um/sec within the capillary structures. We conclude that the development of ectopic lymphoid tissue requires significant structural remodeling of the stromal microcirculation. A feature of permissive tissues may be the capacity for lymphoid angiogenesis. PMID:19382226

  18. Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice

    PubMed Central

    Sliva, Daniel; Loganathan, Jagadish; Jiang, Jiahua; Jedinak, Andrej; Lamb, John G.; Terry, Colin; Baldridge, Lee Ann; Adamec, Jiri; Sandusky, George E.; Dudhgaonkar, Shailesh

    2012-01-01

    Background Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice. Methods/Principal Findings Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue. Conclusions Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer. PMID:23118901

  19. Ulcerative Colitis and Its Association with Salmonella Species

    PubMed Central

    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

  20. Update on ischemic colitis: from etiopathology to treatment including patients of intensive care unit.

    PubMed

    Doulberis, Michael; Panagopoulos, Periklis; Scherz, Stephanie; Dellaporta, Erminia; Kouklakis, Georgios

    2016-08-01

    Ischemic colitis is the result of colonic hypoperfusion and is regarded as a relatively rare condition. It can be roughly classified as occlusive and non-occlusive. Pathogenesis includes a usually transient compromise in the colonic vasculature, with a parallel activation of an inflammatory cascade caused primarily by reperfusion. Diagnosis of ischemic colitis remains often difficult and requires a combination of diagnostic techniques, whereas clinical signs are occasionally only seen late as complications. Gold standard is considered to be colonoscopy. Clinical presentation and treatment of ischemic colitis vary widely depending on the degree of ischemia. Patients of intensive care unit (ICU) with ischemic colitis are often under-diagnosed, since the parallel co-morbidities and the nonspecific nature of symptoms that mimic almost any abdominal pathology, can mislead the doctor. Moreover, sedated or ventilated patients can mask many of the characteristic features of ischemic colitis and make the diagnosis challenging. Bedside colonoscopy and diagnostic laparoscopy in ICUs are two options, which seem lately to be reliable and promising in diagnosing ischemic colitis in critically ill patients. PMID:27152750

  1. Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis

    PubMed Central

    Cui, Xiangli; Jin, Yu; Poudyal, Deepak; Chumanevich, Alexander A.; Davis, Tia; Windust, Anthony; Hofseth, Anne; Wu, Wensong; Habiger, Joshua; Pena, Edsel; Wood, Patricia; Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Hofseth, Lorne

    2010-01-01

    We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage. We found there were 82 protein end points that were either significantly higher (41 proteins) or significantly lower (41 proteins) in the AOM + DSS group compared with the AOM-alone (control) group. In contrast, there were only 19 protein end points that were either significantly higher (10 proteins) or significantly lower (9 proteins) in the AOM + DSS + AG group compared with the AOM-alone (control) group. Overall, these results suggest that AG keeps the colon environment in metabolic equilibrium when mice are treated with AOM + DSS and gives insight into the mechanisms by which AG protects from colon cancer associated with colitis. PMID:20729391

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

    PubMed

    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

  3. Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine.

    PubMed

    Madara, J L; Podolsky, D K; King, N W; Sehgal, P K; Moore, R; Winter, H S

    1985-01-01

    Chronic colitis in the cotton-top tamarin (CTT) has been characterized by obtaining distal colonic biopsy specimens, hematocrits, serum albumins, and stools for bacteriologic and parasitic examination in nondebilitated living CTTs. The species specificity of the histologic features of colitis observed in the CTT was assessed by obtaining distal colonic biopsy specimens from 10 animals of other primate species for histologic examination. Histologic evidence of active colitis was found in 50% of adult CTTs but was absent in all non-CTT species studied. Forty-two stool samples obtained from 18 CTTs yielded only one isolate (Campylobacter). In addition to active colitis, CTT rectal mucosa also often had subtle irregularities in mucosal structure that were not present in nonrelated primate species and might represent chronic colitis. Metaplasia was not observed. The therapeutic effects of oral sulfasalazine (50 mg/kg X day) on CTT colitis were assessed in a randomized 10-wk placebo controlled crossover study. This study demonstrated significant improvement in disease activity as judged histologically (p less than 0.05) and significant increases in animal weight (p less than 0.01) and serum albumin (p less than 0.01) during sulfasalazine therapy when compared with saline control. Sulfasalazine therapy can ameliorate the effects of this disease and offers promise in maintaining experimental colonies of this endangered species for future studies. PMID:2856876

  4. 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

  5. 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.

  6. 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

  7. 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

  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. CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice.

    PubMed

    Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Torkvist, Leif; Halfvarson, Jonas; Yan, Yutao; Laroui, Hamed; Shmerling, Doron; Tallone, Tiziano; D'Amato, Mauro; Sitaraman, Shanthi V; Merlin, Didier

    2011-05-01

    Expression of the transmembrane glycoprotein CD98 (encoded by SLC3A2) is increased in intestinal inflammatory conditions, such as inflammatory bowel disease (IBD), and in various carcinomas, yet its pathogenetic role remains unknown. By generating gain- and loss-of-function mouse models with genetically manipulated CD98 expression specifically in intestinal epithelial cells (IECs), we explored the role of CD98 in intestinal homeostasis, inflammation, and colitis-associated tumorigenesis. IEC-specific CD98 overexpression induced gut homeostatic defects and increased inflammatory responses to DSS-induced colitis, promoting colitis-associated tumorigenesis in mice. Further analysis indicated that the ability of IEC-specific CD98 overexpression to induce tumorigenesis was linked to its capacity to induce barrier dysfunction and to stimulate cell proliferation and production of proinflammatory mediators. To validate these results, we constructed mice carrying conditional floxed Slc3a2 alleles and crossed them with Villin-Cre mice such that CD98 was downregulated only in IECs. These mice exhibited attenuated inflammatory responses and resistance to both DSS-induced colitis and colitis-associated tumorigenesis. Together, our data show that intestinal CD98 expression has a crucial role in controlling homeostatic and innate immune responses in the gut. Modulation of CD98 expression in IECs therefore represents a promising therapeutic strategy for the treatment and prevention of inflammatory intestinal diseases, such as IBD and colitis-associated cancer. PMID:21490400

  10. 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

  11. Recurrent refractory Clostridium difficile colitis treated successfully with rifaximin and tigecycline: a case report and review of the literature.

    PubMed

    El-Herte, Rima I; Baban, Tania A; Kanj, Souha S

    2012-03-01

    Clostridium difficile colitis infection is on the rise and is considerably increasing the duration of hospital stay, as well as healthcare costs. The management of C. difficile colitis has become more challenging with the increasing failure of therapeutic response to metronidazole and oral vancomycin. Tigecycline is a new glycylcycline that has shown in vitro activity against C. difficile. We report herein a case of C. difficile colitis that failed to improve on a combination of metronidazole and oral vancomycin. The patient subsequently developed a surgical abdomen secondary to refractory C. difficile colitis, but was successfully treated with a combination of rifaximin and tigecycline after she refused to undergo surgical treatment. PMID:22077098

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

    PubMed

    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

  13. Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn’s colitis

    PubMed Central

    Johnson, D. H.; Khanna, S.; Smyrk, T. C.; Loftus, E. V.; Anderson, K. S.; Mahoney, D. W.; Ahlquist, D. A.; Kisiel, J. B.

    2016-01-01

    SUMMARY Background Chronic ulcerative colitis (CUC) and colonic Crohn’s disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk. Aim To assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single-centre cohort study. Methods Patients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006–12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan–Meier method. Results Between 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010–12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0–30%) and 30% (3–57%), respectively, in SEC patients compared to 4% (0–12%) and 9% (0–23%), respectively, in CUC or CD controls (P = 0.047, log-rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09). Conclusions Serrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn’s disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship. PMID:24779703

  14. Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

    PubMed Central

    Price, Gareth R; Tauro, Sharyn B; Taupin, Douglas; Thornton, David J; Png, Chin Wen; Crockford, Tanya L; Cornall, Richard J; Adams, Rachel; Kato, Masato; Nelms, Keats A; Hong, Nancy A; Florin, Timothy H. J; Goodnow, Christopher C; McGuckin, Michael A

    2008-01-01

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

  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. Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model.

    PubMed

    Oz, Helieh S; Chen, Theresa S; Nagasawa, Herbert

    2007-08-01

    Oxidant-mediated injury plays an important role in the pathophysiology of inflammatory bowel disease (IBD). Recently, antioxidants were shown to modulate colitis in mice. In this study, the protective effects of L-cysteine and glutathione (GSH) prodrugs are further evaluated against progression of colitis in a murine model. ICR mice were fed compounds incorporated into chow as follows: Group (A) received chow supplemented with vehicle. Group (B) was provided 2-(RS)-n-propylthiazolidine-4(R)-carboxylic-acid (PTCA), a cysteine prodrug. Group (C) received D-ribose-L-cysteine (RibCys), another cysteine prodrug that releases L-cysteine. Group (D) was fed L-cysteine-glutathione mixed sulfide (CySSG), a ubiquitous GSH derivative present in mammalian cells. After 3 days, the animals were further provided with normal drinking water or water supplemented with dextran sodium sulfate (DSS). Mice administered DSS developed severe colitis and suffered weight loss. Colonic lesions significantly improved in animals treated with PTCA and RibCys and, to a lesser extent, with CySSG therapy. Hepatic GSH levels were depleted in colitis animals (control vs DSS, P < 0.001), and normalized with prodrug therapies (control vs treatments, P > 0.05). Protein expressions of serum amyloid A and inflammatory cytokines [interleukin (IL)-6, IL-12, tumor necrosis factor-alpha (TNF-alpha), osteopontin (OPN)] were significantly increased in colitis animals and improved with therapies. Immunohistochemistry and Western blot analyses showed significant upregulation of the macrophage-specific markers, COX-2 and CD68, which suggests macrophage activation and infiltration in the colonic lamina propria in colitis animals. These abnormalities were attenuated in prodrug-treated mice. In conclusion, these data strongly support the novel action of the PTCA against colitis, which further supports a possible therapeutic application for IBD patients. PMID:17656332

  17. 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.

  18. The Role of Surgery in the Management of Patients With Refractory Chronic Granulomatous Disease Colitis

    PubMed Central

    Alvarez-Downing, Melissa M.; Kamal, Natasha; Inchauste, Suzanne M.; Khangura, Sajneet K.; Malech, Harry L.; Holland, Steven M.; Hughes, Marybeth S.; Heller, Theo; Sherry, Richard M.

    2012-01-01

    Background Chronic granulomatous disease is a rare immunodeficiency complicated by dysregulated inflammation and granulomatous complications of the gastrointestinal tract. The management of chronic granulomatous disease colitis presents the dilemma of an immunocompromised host requiring immunosuppressive therapy which can potentiate fatal infections. Objective To identify the types of gastrointestinal surgery performed in patients and determine the role of surgery in the management of refractory colitis. Design and Settings A retrospective single institution chart review was performed. Patients Of 268 patients with chronic granulomatous disease treated at the National Institutes of Health between 1985 and 2011, 98 (37%) were identified as having colitis; 27 (10%) had a history of gastrointestinal luminal surgery. Main outcome measures Patient characteristics, type of gastrointestinal surgery and clinical outcomes were documented. Results A total of 62 gastrointestinal luminal surgeries were performed in 27 patients with chronic granulomatous disease and colitis. All 27 had a history of perineal disease requiring intervention. Four (15%) had additional surgery performed for reasons other than colitis. Otherwise, 12 (44%) had surgery limited to the perineum, 2 (7%) had a segmental resection and 13 (48%) underwent fecal diversion with ileostomy or colostomy. Despite local procedures, 7 (58%) patients in the perineal only group remained symptomatic. Both patients with a segmental resection had persistent perineal disease and 1 had a recurrent colovesicular fistula. Of the 13 ostomy patients, 11 initially received a diverting ostomy. Eight (73%) of these ultimately required additional procedures for refractory disease and 4 (36%) developed peristomal pyoderma gangrenosum. Four patients who underwent proctocolectomy with end ileostomy, either initially (2) or as a definitive procedure (2), experienced resolution of colitis and perineal disease. Limitations This study is

  19. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival

    PubMed Central

    Loftus, E; Silverstein, M; Sandborn, W; Tremaine, W; Harmsen, W; Zinsmeister, A

    2000-01-01

    BACKGROUND—There is significant geographic variation in the reported incidence of ulcerative colitis.
AIMS—To update the incidence and prevalence of ulcerative colitis in Olmsted County, Minnesota, examine temporal trends, and determine overall survival.
PATIENTS—All Olmsted County residents diagnosed with ulcerative colitis between 1940 and 1993 (incidence cases), and all residents with ulcerative colitis alive on 1 January 1991 (prevalence cases).
METHODS—Incidence and prevalence rates were adjusted using 1990 US census figures for whites. The effects of age, sex, and calendar year on incidence rates were evaluated using Poisson regression. Survival from diagnosis was compared with that expected for US north-central whites.
RESULTS—Between 1940 and 1993, 278 incidence cases were identified, for an adjusted incidence rate of 7.6 cases per 100 000 person years (95% confidence interval (CI), 6.7 to 8.5). On 1 January 1991, there were 218 residents with definite or probable ulcerative colitis, for an adjusted prevalence rate of 229 cases per 100 000 (95% CI, 198 to 260). Increased incidence rates were associated with later calendar years (p<0.002), younger age (p<0.0001), urban residence (p<0.0001), and male sex (p<0.003). Overall survival was similar to that expected (p>0.2).
CONCLUSIONS—The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter. Incidence rates among men and urban residents were significantly higher. The prevalence rate in Rochester in 1991 was 19% higher than that in 1980. Overall survival was similar to that of the general population.


Keywords: ulcerative colitis; incidence; prevalence; survival; prognosis; epidemiology PMID:10673294

  20. 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. PMID:26479868

  1. 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. PMID:25332518

  2. Diagnostic Value of Fecal Calprotectin in Patient with Ulcerative Colitis

    PubMed Central

    Zamani, Hamed; Barzin, Gilda; Yousefinia, Mahsa; Mohammadkhani, Ashraf; Ostovaneh, Mohammad Reza; Sharifi, Amir Houshang; Tayebi, Sirous; Malekzadeh, Reza; Ansari, Reza

    2013-01-01

    BACKGROUND Ulcerative colitis (UC) is characterized by recurrent episodes of inflammation limited to the mucosal layer of the colon. Calprotectin is a zinc and calcium binding protein derived from neutrophils and monocytes. It is easily detectable in tissue samples, body fluids, and stools, which makes it a potentially valuable marker of inflammation. The aim of the current study is to evaluate the value of fecal calprotectin (FC) as a marker of disease activity in patients with UC. METHODS Seventy three eligible subjects underwent ileocolonoscopy and multiple biopsies were obtained from different parts of the colon and terminal ileum. All patients underwent blood and stool sampling as well as an interview to assess the disease severity utilizing ulcerative colitis activity index (UCAI), subjectively. The diagnostic value of the FC in comparison with Mayo disease activity index as the gold standard technique, was then evaluated. RESULTS Mean FC level increased linearly according to Mayo disease activity index (r=0.44, p<0.001) and was significantly different between levels of Mayo disease activity index (p=0.003). In multivariate analysis, Mayo disease activity index, positive CRP and ESR were associated with FC level. FC level > 21.4 ng/ml was able to discriminate between active and inactive phases of UC according to Mayo disease activity index>2 with 72.3% sensitivity and 73.1% specificity. The combination of FC > 21.4 ng/ml and UCAI score of 7 had a 46.8% sensitivity and 88% specificity to diagnose Mayo disease activity index >2. Furthermore, FC level <21.4 ng/ml in combination with UCAI score of <3 showed a highly considerable specificity of 98% to discriminate the remission phase of UC (Mayo disease activity index <2), although with a low sensitivity (31%). CONCLUSION FC appears to be a non-invasive biomarker with moderate accuracy to discriminate the active phase of inflammatory bowel disease (IBD). The value of FC especially in combination with UCAI is

  3. 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

  4. Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis.

    PubMed

    Aghdassi, E; Carrier, J; Cullen, J; Tischler, M; Allard, J P

    2001-05-01

    In this study, we investigated the effect of intraperitoneal iron dextran (100 mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma alpha-tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats. PMID:11341654

  5. Comparison of the composition of faecal fluid in Crohn's disease and ulcerative colitis.

    PubMed Central

    Schilli, R; Breuer, R I; Klein, F; Dunn, K; Gnaedinger, A; Bernstein, J; Paige, M; Kaufman, M

    1982-01-01

    We determined the ionic composition of faecal fluid from 13 patients with Crohn's disease limited to the colon, 10 with diffuse ulcerative colitis, and eight with ulcerative proctitis. The Crohn's and colitis groups had similar proportions of colon surface involved radiographically and similar 24 hour faecal weights. However, Crohn's patients' faecal fluid had arithmetically lower mean sodium and statistically lower mean chloride (34.8 mmol/l +/- 16.2 SD vs. 53.1 mmol/l +/- 23.1 SD) and higher potassium (49.2 mmol/l +/- 20.2 SD vs. 33.0 mmol/l +/- 13.8 SD) concentrations (p less than 0.05 for each) and much higher osmolality (487.1 mOsmol/kg +/- 87.1 SD vs. 341.1 mOsmol/kg +/- 88.9 SD, p less than 0.001). Separation of these patients using the faecal osmotic gap agreed with the clinical classification in 86% of cases. The diarrhoea of proctitis patients had a nearly normal ionic composition which was clearly distinguishable from that of diffuse colitis. These results suggest differences in the composition and perhaps the pathogenesis of the diarrhoea of Crohn's and ulcerative colitis. The composition of fluid may prove a useful, non-invasive method for classifying patients with inflammatory bowel disease and, in ulcerative colitis, determining the extent of the inflammatory process. PMID:7076010

  6. Beneficial Effects of Maprotiline in a Murine Model of Colitis in Normal and Reserpinised Depressed Rats

    PubMed Central

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

    2014-01-01

    Background. Anti-inflammatory and immunomodulatory activities have been reported for maprotiline, a strong norepinephrine reuptake inhibitor. In addition, some other antidepressant drugs have shown beneficial effects in experimental colitis. Methods. All the animals were divided into normal and depressed groups. In normal rats colitis was induced by instillation of 2 mL of 4% acetic acid and after 2 hours, maprotiline (10, 20, and 40 mg/kg, i.p.) was administered. In reserpinised depressed rats, depression was induced by injection of reserpine (6 mg/kg, i.p.), 1 h prior to colitis induction, and then treated with maprotiline (10, 20, and 40 mg/kg). Treatment continued daily for four days. Dexamethasone (1 mg/kg, i.p.) was given as a reference drug. On day five following colitis induction, animals were euthanized and distal colons were assessed macroscopically, histologically, and biochemically (assessment of myeloperoxidase activity). Results. Maprotiline significantly improved macroscopic and histologic scores and diminished myeloperoxidase activity in both normal and depressed rats while reserpine exacerbated the colonic damage. Conclusion. Our data suggests that the salutary effects of maprotiline on acetic acid colitis 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:27355055

  7. Probiotics increase T regulatory cells and reduce severity of experimental colitis in mice

    PubMed Central

    Zhao, Hai-Mei; Huang, Xiao-Ying; Zuo, Zhi-Qin; Pan, Qi-Hong; Ao, Mei-Ying; Zhou, Feng; Liu, Hong-Ning; Liu, Zhi-Yong; Liu, Duan-Yong

    2013-01-01

    AIM: To investigate the effect of probiotics on regulating T regulatory cells and reducing the severity of experimental colitis in mice. METHODS: Forty C57/BL mice were randomly divided into four groups. Colitis was induced in the mice using 2,4,6-trinitrobenzene sulfonic acid (TNBS). After 10-d treatment with Bifico capsules (combined bifidobacterium, lactobacillus and enterococcus), body weight, colonic weight, colonic weight index, length of colon, and histological scores were evaluated. CD4+CD25+Foxp3+T cell in mesenteric lymph nodes were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed by a cytometric bead array. RESULTS: The colonic weight index and the colonic weight of colitis mice treated with Bifico were lower than that of TNBS-induced mice without treatment. However, colonic length and percent of body weight amplification were higher than in TNBS-induced mice without treatment. Compared with TNBS-induced mice without treatment, the level of CD4+CD25+Foxp3+T cells in mesenteric lymph nodes, the expression of interleukin (IL)-2, IL-4 and IL-10 in colonic tissues from colitis mice treated with Bifico were upregulated, and tumor necrosis factor-α and interferon-γ were downregulated. CONCLUSION: Probiotics effectively treat experimental colitis by increasing CD4+CD25+Foxp3+T cell and regulating the balance of Th1 and Th2 cytokines in the colonic mucosa. PMID:23430765

  8. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis

    PubMed Central

    Khounlotham, Manirath; Kim, Wooki; Peatman, Eric; Nava, Porfirio; Medina-Contreras, Oscar; Addis, Caroline; Koch, Stefan; Fournier, Benedicte; Nusrat, Asma; Denning, Timothy L.; Parkos, Charles A.

    2012-01-01

    SUMMARY Mice lacking Junctional Adhesion Molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r-/-Rag1-/- mice to acute colitis. Although negligible contributions of adaptive immunity in F11r-/-Rag1-/- mice were observed, F11r-/-Rag1-/- mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-β-producing CD4+ T cells in F11r-/- mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4+ T cells and TGF-β. Absence of IgA in F11r+/+Igha-/- mice did not affect disease whereas F11r-/-Igha-/- mice displayed markedly increased susceptibility to acute injury induced colitis. These data establish a role for adaptive immune mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise. PMID:22981539

  9. The role of early colonoscopy in CMV colitis of transplant recipients.

    PubMed

    Korkmaz, M; Kunefeci, G; Selcuk, H; Unal, H; Gur, G; Yilmaz, U; Arslan, H; Demirhan, B; Boyacioglu, S; Haberal, M

    2005-09-01

    Cytomegalovirus (CMV)-associated diseases remain a major problem in transplant recipients. Early diagnosis is critical. Presentation of early CMV colitis can be mild and nonspecific in transplant recipients. Although serology is helpful in the diagnosis, sometimes it is inadequate. Because the endoscopic features of CMV colitis are specific, colonoscopy facilitates the histopathologic examination. We present the clinical properties and advantages of early colonoscopy in transplant recipients with CMV colitis. The study group included seven patients (six men, one woman of mean age, 36.7 years (range, 22 to 64 years) whose mean transplant duration was 12.3 months (range, 1 to 72 months). Six of the seven patients experienced an acute graft rejection treated with high doses of steroids; one patient had a herpes simplex virus infection. All patients were on steroid treatment with a various combinations of immunosuppressive agents, including cyclosporine, mycophenolate mofetil, and tacrolimus. All patients presented with mild diarrhea without any blood or mucous discharge. Four patients had fever exceeding 38 degrees C; two had abdominal pain. Stool examinations revealed normal findings in six patients, while one patient had white blood cells and amoebic cysts. Serum CMV IgM and CMV pp65 antigenemia were negative in five of seven patients and two had positive results. All patients showed typical colonoscopic and histopathologic findings compatible with CMV colitis. Standard ganciclovir treatment was successful in all patients. Early and rapid colonoscopy is beneficial for the early diagnosis and management of CMV colitis in transplant recipients. PMID:16213304

  10. Management of difficult-to-treat patients with ulcerative colitis: focus on adalimumab

    PubMed Central

    Armuzzi, Alessandro; Pugliese, Daniela; Nardone, Olga Maria; Guidi, Luisa

    2013-01-01

    The treatment of ulcerative colitis has changed over the last decade, with the introduction of biological drugs. This article reviews the currently available therapies for ulcerative colitis and the specific use of these therapies in the management of patients in different settings, particularly the difficult-to-treat patients. The focus of this review is on adalimumab, which has recently obtained approval by the European Medicines Agency and the US Food and Drug Administration, for use in treating adult patients with moderate-to-severe, active ulcerative colitis, who are refractory, intolerant, or who have contraindications to conventional therapy, including corticosteroids and thiopurines. Since the results emerging from the pivotal trials have been subject to some debate, the aim of this review was to summarize all available data on the use of adalimumab in ulcerative colitis, focusing also on a retrospective series of real-life experiences. Taken together, the current evidence indicates that adalimumab is effective for the treatment of patients with different types of ulcerative colitis, including biologically naïve and difficult-to-treat patients. PMID:23630414

  11. 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

  12. 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

  13. The Matricellular Protein CCN1 Promotes Mucosal Healing in Murine Colitis through IL-6

    PubMed Central

    Choi, Jacob S.; Kim, Ki-Hyun; Lau, Lester F.

    2015-01-01

    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 Ccn1dm/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. Ccn1dm/dm mice exhibited high mortality, impaired mucosal healing, and diminished IL-6 expression during the repair phase of DSS-induced colitis compared to 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 Ccn1dm/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. PMID:25807183

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

    PubMed Central

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

    2014-01-01

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

  15. Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer

    PubMed Central

    Liang, Xujun; Li, Huiying; Tian, Geng; Li, Shao

    2014-01-01

    Bacterial colonisation of the gut is involved in the development of colitis-associated colorectal cancer. However, it remains unclear how the gut microbiota dynamically shifts correlating with colorectal carcinogenesis. Here, we reveal the longitudinal shifts in the microbial community that occur with colitis-associated colorectal cancer. High-throughput sequencing results for the bacterial 16S rRNA gene (V3 region) were compared for azoxymethane/dextran sodium sulphate-treated mice and control mice. We found that microbial community structure was significantly altered by chronic colitis. Microbes in the species Streptococcus luteciae, Lactobacillus hamster, Bacteroides uniformis and Bacteroides ovatus were increased during colorectal carcinogenesis. Histological measurements for a molecular network including six interconnected key factors from inflammation to cancer, namely p65, p53, COX-2, PPARγ, CCR2 and β-catenin, indicated that the microbiome modifications were correlated with molecular pathogenesis of colitis-associated colorectal cancer. Phylotype modifications after each AOM/DSS cycle were identified. A longitudinal microbial network was then constructed for the gut microbiome and showed that the phylotype shifts during this process were complex and highly dynamic. This work may provide a deeper understanding of the role of the microbiota and microbe-host interactions in colitis-associated colorectal cancer. PMID:24828543

  16. 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. PMID:25007240

  17. Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer.

    PubMed

    Liang, Xujun; Li, Huiying; Tian, Geng; Li, Shao

    2014-01-01

    Bacterial colonisation of the gut is involved in the development of colitis-associated colorectal cancer. However, it remains unclear how the gut microbiota dynamically shifts correlating with colorectal carcinogenesis. Here, we reveal the longitudinal shifts in the microbial community that occur with colitis-associated colorectal cancer. High-throughput sequencing results for the bacterial 16S rRNA gene (V3 region) were compared for azoxymethane/dextran sodium sulphate-treated mice and control mice. We found that microbial community structure was significantly altered by chronic colitis. Microbes in the species Streptococcus luteciae, Lactobacillus hamster, Bacteroides uniformis and Bacteroides ovatus were increased during colorectal carcinogenesis. Histological measurements for a molecular network including six interconnected key factors from inflammation to cancer, namely p65, p53, COX-2, PPARγ, CCR2 and β-catenin, indicated that the microbiome modifications were correlated with molecular pathogenesis of colitis-associated colorectal cancer. Phylotype modifications after each AOM/DSS cycle were identified. A longitudinal microbial network was then constructed for the gut microbiome and showed that the phylotype shifts during this process were complex and highly dynamic. This work may provide a deeper understanding of the role of the microbiota and microbe-host interactions in colitis-associated colorectal cancer. PMID:24828543

  18. 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. PMID:26089223

  19. Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice.

    PubMed

    Yang, Yang; He, Jiao; Suo, Yuan; Zheng, Zongwei; Wang, Jingjing; Lv, Le; Huo, Chuanchuan; Wang, Ziye; Li, Jing; Sun, Wenji; Zhang, Yongmin

    2016-07-01

    Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60mg/kg) and sulfasalazine (500mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1β, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice. PMID:27179450

  20. Phosphatase Wip1 Masters IL-17-producing Neutrophil-mediated Colitis in Mice.

    PubMed

    Hu, Xuelian; Wang, Peng; Du, Junfeng; Yang, Fan; Tian, Yuan; Shen, Xiaofei; Yang, Tao; Zhang, Lianfeng; Zhao, Yong

    2016-06-01

    Wild-type p53-induced phosphatase 1 (Wip1) is currently believed to be a promising drug target for cancer therapy. Our recent studies showed that deletion of Wip1 remarkably promoted neutrophil inflammatory response. Whether Wip1 is involved in the regulation of inflammatory bowel disease is unknown. In the present study, we found that Wip1 knockout (KO) mice were more susceptible to colitis induced by dextran sulphate sodium (DSS) than wild-type mice as substantiated by the lower mouse survival ratio, rapid bodyweight loss, increased disease activity index, shorter colon length, and more severe pathology of colons in Wip1KO mice. Using full bone marrow chimera mouse models, we demonstrated that Wip1 intrinsically controls inflammatory response of immune cells. Deletion of IL-17 (Wip1/IL-17 double KO mice) significantly rescued the pathology in Wip1KO mice. Neutrophils of DSS-treated wild-type and Wip1KO mice expressed significantly higher IL-17. After adoptive transfer of sorted Wip1KO or double KO neutrophils into IL-17KO mice, mice receiving double KO neutrophils were more resistant to DSS-induced colitis than mice receiving Wip1KO neutrophils. These data collectively indicate that Wip1 modulates host sensitivity to colitis by intrinsically regulating immune cells. The enhanced IL-17 expression in neutrophils contributed to the increased sensitivity and severity of colitis in Wip1KO mice. Thus, Wip1 may be used as a drug target to treat colitis. PMID:26950306

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

    PubMed

    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

  2. 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

  3. Ischemic Colitis Is a Common Cause of Severe Hematochezia and Patient Outcomes Are Worse Than with Other Colonic Diagnoses

    PubMed Central

    Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O.G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.

    2013-01-01

    Background Outcomes of severe hematochezia from ischemic colitis vs. other colonic diagnoses have not been well studied. Objective Our purposes were: 1) to compare demographics and outcomes of patients hospitalized with severe hematochezia from ischemic colitis vs. other colonic diagnoses, 2) to compare inpatient vs. outpatient start of bleeding from ischemic colitis, 3) to describe potential risk factors. Design Prospective cohort study. Setting Tertiary referral academic centers. Patients Patients referred for gastroenterology consultation about severe hematochezia. Interventions Colonoscopic therapy was provided as indicated. Main outcome measurements Rebleeding, surgery and length of hospital stay Results Of 550 patients in the last 12 years with severe colonic hematochezia, 65 were caused by ischemia. Major 30 day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Patients with inpatient (vs. outpatient) ischemic colitis had significantly more and severe comorbidities at baseline and significantly higher rates of rebleeding, surgery & more hospital & intensive care unit days. Limitations Two-center study Conclusions Ischemic colitis was found more often in females and patients with anticoagulant usage, severe lung disease, higher creatinine, higher glucose, & more fresh frozen plasma transfused. Five patients with focal lesions had colonoscopic hemostasis. Major 30 day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Comparing outpatient vs. inpatient start of ischemic colitis, inpatients had significantly worse outcomes. PMID:21839438

  4. 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...

  5. Array Comparative Genomic Hybridization in Ulcerative Colitis Neoplasia: Single Non-Dysplastic Biopsies Distinguish Progressors from Non-Progressors

    PubMed Central

    Bronner, Mary P.; Skacel, Marek; Crispin, David A.; Hoff, Peter D.; Emond, Mary J.; Lai, Lisa A.; Tubbs, Raymond R.; Rabinovitch, Peter S.; Brentnall, Teresa A.

    2010-01-01

    Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At present, identification of this subset is markedly limited and necessitates lifelong colonoscopic surveillance for the entire ulcerative colitis population. Better risk markers are needed to focus surveillance onto the patients most likely to benefit. Using array-based comparative genomic hybridization, we analyzed single, non-dysplastic biopsies from three patient groups: ulcerative colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance of 18 cm from the analyzed site; ulcerative colitis nonprogressors (n=8) without dysplasia during long-term surveillance; and non-ulcerative colitis normal controls (n=2). Genomic DNA from fresh colonic epithelium purified from stroma was hybridized to 287 (low-density) and 4,342 (higher-density) feature bacterial artificial chromosome arrays. Sample-to-reference fluorescence ratios were calculated for individual chromosomal targets and globally across the genome. The low-density arrays yielded pronounced genomic gains and losses in 3 of 9 (33%) ulcerative colitis progressors but in none of the 10 control patients. Identical DNA samples analyzed on the higher density arrays, using a combination of global and individual high variance assessments, distinguished all 9 progressors from all 10 controls. These data confirm that genomic alterations in ulcerative colitis progressors are widespread, even involving single non-dysplastic biopsies far distant from neoplasia. They therefore show promise toward eliminating full colonoscopic surveillance with extensive biopsy sampling in the majority of ulcerative colitis patients. PMID:20802465

  6. Herbal Medicine in the Treatment of Ulcerative Colitis

    PubMed Central

    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. PMID:22249085

  7. Idelalisib-associated Colitis: Histologic Findings in 14 Patients.

    PubMed

    Weidner, Anna-Sophie; Panarelli, Nicole C; Geyer, Julia T; Bhavsar, Erica B; Furman, Richard R; Leonard, John P; Jessurun, Jose; Yantiss, Rhonda K

    2015-12-01

    Idelalisib is an inhibitor of the PI3Kδ isoform approved for treatment of patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Many patients develop gastrointestinal symptoms during idelalisib therapy; however, the pathologic effects of this drug have not been characterized. We identified 50 patients who received at least 3 months of idelalisib therapy. Clinical findings and symptoms were noted for each patient, and endoscopic findings were recorded for those who underwent colonoscopic examination. Hematoxylin and eosin-stained sections from colonic biopsy samples were evaluated for histologic patterns of injury. Twenty-three (46%) patients experienced diarrhea during treatment with idelalisib, including 8 with severe symptoms (≥7 stools/d above baseline and/or requiring hospitalization). Fourteen patients underwent colonoscopic examination with mucosal biopsy. Twelve (86%) of these had colitis characterized by intraepithelial lymphocytosis, crypt cell apoptosis, and neutrophilic infiltration of crypt epithelium. Eleven patients had symptoms severe enough to warrant drug withdrawal, including 9 who were also treated with corticosteroids. Idelalisib commonly causes diarrheal symptoms in patients undergoing therapy for B-cell neoplasia, which may be severe in nearly 20% of patients. Characteristic histologic features include the combination of intraepithelial lymphocytosis and crypt cell apoptosis, often accompanied by neutrophils. Discontinuation of the drug results in symptomatic improvement and resolution of histologic changes. PMID:26448188

  8. 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

  9. Emerging Treatment Options in Mild to Moderate Ulcerative Colitis

    PubMed Central

    Lichtenstein, Gary R.; Hanauer, Stephen B.; Sandborn, William J.

    2015-01-01

    Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas. PMID:26491415

  10. Acute ischemic colitis secondary to air embolism after diving

    PubMed Central

    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. PMID:22096777

  11. Increased levels of homocysteine in patients with ulcerative colitis

    PubMed Central

    Akbulut, Sabiye; Altiparmak, Emin; Topal, Firdevs; Ozaslan, Ersan; Kucukazman, Metin; Yonem, Ozlem

    2010-01-01

    AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thromboembolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). When multivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events. PMID:20480528

  12. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy

    PubMed Central

    Pillet, Sylvie; Pozzetto, Bruno; Roblin, Xavier

    2016-01-01

    The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease. PMID:26877608

  13. Indole compounds may be promising medicines for ulcerative colitis.

    PubMed

    Sugimoto, Shinya; Naganuma, Makoto; Kanai, Takanori

    2016-09-01

    Indole compounds are extracted from indigo plants and have been used as blue or purple dyes for hundreds of years. In traditional Chinese medicine, herbal agents in combination with Qing-Dai (also known as indigo naturalis) have been used to treat patients with ulcerative colitis (UC) and to remedy inflammatory conditions. Recent studies have noted that indole compounds can be biosynthesized from tryptophan metabolites produced by various enzymes derived from intestinal microbiota. In addition to their action on indole compounds, the intestinal microbiota produce various tryptophan metabolites that mediate critical functions through distinct pathways and enzymes. Furthermore, some indole compounds, such as indigo and indirubin, act as ligands for the aryl hydrocarbon receptor. This signaling pathway stimulates mucosal type 3 innate lymphoid cells to produce interleukin-22, which induces antimicrobial peptide and tight junction molecule production, suggesting a role for indole compounds during the mucosal healing process. Thus, indole compounds may represent a novel treatment strategy for UC patients. In this review, we describe the origin and function of this indole compound-containing Chinese herb, as well as the drug development of indole compounds. PMID:27160749

  14. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy.

    PubMed

    Pillet, Sylvie; Pozzetto, Bruno; Roblin, Xavier

    2016-02-14

    The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease. PMID:26877608

  15. Resolution of Severe Ulcerative Colitis with the Specific Carbohydrate Diet.

    PubMed

    Khandalavala, Birgit N; Nirmalraj, Maya C

    2015-01-01

    A 73-year-old female of Asian origin was diagnosed with ulcerative colitis (UC) after initial gastrointestinal symptoms of abdominal pain and bloody diarrhea. She had a relatively benign course over the subsequent 12 years. In 2009, she had increased left-sided abdominal pain, bloody diarrhea and progressive weight loss, due to a severe exacerbation. In spite of a variety of standard treatments, her condition continued to decline with a significant impact on normal life and functioning. In December of 2010, repeat colonoscopy and microscopy confirmed pancolitis, without diverticulitis. The Specific Carbohydrate Diet (SCD) was initiated due to failure of conventional therapies. Following this highly restricted diet, within a period of 3-6 months, improvement was noted, and within a year, no abdominal pain or diarrhea were present, and she returned to her baseline functioning and career. Two years later, repeat colonoscopy showed resolution of the pancolitis, confirmed with microscopic evaluation. Successful use of the SCD in children with UC has been documented. We describe previously unreported, highly beneficial results with both symptomatic and clinical improvement and complete remission of UC in an adult female with the SCD. PMID:26351419

  16. Pros and Cons of Medical Management of Ulcerative Colitis

    PubMed Central

    Navaneethan, Udayakumar; Shen, Bo

    2010-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC. PMID:22131893

  17. Fecal Calprotectin and Clinical Disease Activity in Pediatric Ulcerative Colitis

    PubMed Central

    Kolho, Kaija-Leena; Turner, Dan

    2013-01-01

    Objective. To explore fecal calprotectin levels in pediatric ulcerative colitis (UC) in relation with the validated clinical activity index PUCAI. Methods. This study included all 37 children (median age 14 years) with UC who had calprotectin measured (PhiCal ELISA Test) by the time of PUCAI assessment at the Children's Hospital of Helsinki in a total of 62 visits. Calprotectin values <100 μg/g of stool were considered as normal. The best cut-off value of each measure to predict 3-month clinical outcome was derived by maximizing sensitivity and specificity. Results. In clinically active disease (PUCAI ≥ 10), calprotectin was elevated in 29/32 patients (91% sensitivity). When in clinical remission, 26% (8/30) of the children had normal calprotectin but 7 (23%) had an exceedingly high level (>1000 μg/g). The best cut-off value for calprotectin for predicting poor outcome was 800 μg/g (sensitivity 73%, specificity 72%; area under the ROC curve being 0.71 (95%CI 0.57–0.85)) and for the PUCAI best cut-off values >10 (sensitivity 62%, specificity 64%; area under the ROC curve 0.714 (95%CI 0.58–0.85)). Conclusion. The clinical relevance of somewhat elevated calprotectin during clinical remission in pediatric UC is not known and, until further evidence accumulates, does not indicate therapy escalation. PMID:23533791

  18. Effectiveness of Saccharomyces boulardii in a rat model of colitis

    PubMed Central

    Soyturk, Mujde; Saygili, Saba Mukaddes; Baskin, Huseyin; Sagol, Ozgul; Yilmaz, Osman; Saygili, Fatih; Akpinar, Hale

    2012-01-01

    AIM: To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples. RESULTS: The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P

  19. The role of Budesonide-MMX in active ulcerative colitis.

    PubMed

    Gionchetti, Paolo; Praticò, Chiara; Rizzello, Fernando; Calafiore, Andrea; Capozzi, Nunzia; Campieri, Massimo; Calabrese, Carlo

    2014-03-01

    Traditional corticosteroids represent a well-established and effective treatment for active ulcerative colitis (UC). However, the severity of their systemic side effects, led in recent years to look for new steroid molecules that could reduce them, maximizing the anti-inflammatory activity. Budesonide has been one of the most studied steroid compounds and it has been approved for the treatment of mild to moderate active Crohn's disease (CD). In order to extend the release until the distally located inflammation, budesonide has been coupled with a controlled delivery system, called Multi-Matrix system (MMX), already successfully tested with oral mesalazine for the treatment of distal UC. After in vitro and in vivo models, the efficacy of Budesonide-MMX has been investigated in active UC with a first small phase II study, and partially encouraging results. This article will review the evidences on the use of budesonide in inflammatory bowel diseases and will discuss the role of Budesonide-MMX in active UC nowadays. PMID:24502535

  20. 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

  1. Resolution of Severe Ulcerative Colitis with the Specific Carbohydrate Diet

    PubMed Central

    Khandalavala, Birgit N.; Nirmalraj, Maya C.

    2015-01-01

    A 73-year-old female of Asian origin was diagnosed with ulcerative colitis (UC) after initial gastrointestinal symptoms of abdominal pain and bloody diarrhea. She had a relatively benign course over the subsequent 12 years. In 2009, she had increased left-sided abdominal pain, bloody diarrhea and progressive weight loss, due to a severe exacerbation. In spite of a variety of standard treatments, her condition continued to decline with a significant impact on normal life and functioning. In December of 2010, repeat colonoscopy and microscopy confirmed pancolitis, without diverticulitis. The Specific Carbohydrate Diet (SCD) was initiated due to failure of conventional therapies. Following this highly restricted diet, within a period of 3–6 months, improvement was noted, and within a year, no abdominal pain or diarrhea were present, and she returned to her baseline functioning and career. Two years later, repeat colonoscopy showed resolution of the pancolitis, confirmed with microscopic evaluation. Successful use of the SCD in children with UC has been documented. We describe previously unreported, highly beneficial results with both symptomatic and clinical improvement and complete remission of UC in an adult female with the SCD. PMID:26351419

  2. 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

  3. Florid urticarial vasculitis heralding a flare up of ulcerative colitis.

    PubMed

    Boules, Evon; Lyon, Calum

    2014-01-01

    A 75-year-old man with ulcerative colitis (UC) and diet controlled diabetes mellitus presented with a 3-week history of slightly itchy, red plaques on both lower limbs ascending gradually to cover the trunk and arms. One week later, he developed a flare up of his UC. Routine blood tests showed modest drop in haemoglobin (122 g/L) and C reactive protein (85 mg/L). Serology was remarkable for high antiproteinase 3 (c-ANCA). Serum electrophoresis showed a mildly positive paraprotein band (γ region). Stool culture was negative. Urine analysis showed proteinuria. Skin biopsy showed features of urticarial vasculitis (UV). He underwent a flexible sigmoidoscopy after the flare up showed mildly active UC. The patient was given hydrocortisone for 7 days and then prednisolone. Both rash and UC subsided. Electrophoresis was repeated 4 weeks later showing normal pattern. Prednisolone has been gradually reduced. Although rare, UV can be considered as one of the skin manifestations of UC. PMID:25535230

  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. 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

  6. Effectiveness of Dietary Allergen Exclusion Therapy on Eosinophilic Colitis in Chinese Infants and Young Children ≤ 3 Years of Age

    PubMed Central

    Yang, Min; Geng, Lanlan; Chen, Peiyu; Wang, Fenghua; Xu, Zhaohui; Liang, Cuiping; Li, Huiwen; Fang, Tiefu; Friesen, Craig A.; Gong, Sitang; Li, Dingyou

    2015-01-01

    Eosinophilic colitis is a well recognized clinical entity mainly associated with food allergies. Empiric treatment options include dietary allergen exclusion (extensively hydrolyzed protein formula and elimination diet), anti-allergy medications (antihistamines and leukotriene receptor antagonists) and corticosteroids. We evaluated the effectiveness of dietary antigen exclusion on clinical remission of eosinophilic colitis in infants and young children. We retrospectively reviewed charts of all infants and children ≤3 years of age who were diagnosed with eosinophilic colitis (defined as mucosal eosinophilia ≥20 hpf−1) from 1 January 2011 to 31 December 2013 at a tertiary children’s hospital in China. Forty-nine children were identified with eosinophilic colitis. Elemental formula, simple elimination diet or combination therapy resulted in clinical improvement in 75%, 88.2% and 80% of patients, respectively. In conclusion, eosinophilic colitis in infants and children ≤3 years of age responded well to dietary allergen exclusion. PMID:25768952

  7. [Ulcerous colitis and infection with cytomegalovirus, herpes simplex virus and clostridium difficile].

    PubMed

    Arnold, C; von Sanden, S; Theilacker, C; Blum, H E

    2008-08-01

    The treatment of severe flares of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and in some cases TNF-alpha-antagonists, respectively. These immunosuppressed patients are susceptible for infectious pathogens. Here we report the case of a patient with a severe flare of ulcerative colitis that was first treated with systemic corticosteroids combined with immunomodulators and subsequent with infliximab. The patient then experienced an infection with Clostridium difficile and cytomegalovirus of the colon and a Herpes simplex esophagitis, respectively. After specific treatment the patient responded well to the immunosuppressive therapy. This case illustrates that infections have to be considered before systemic treatment of an acute flare of ulcerative colitis is instituted especially in the case of disease activation during immunosuppressive treatment. PMID:18759202

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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. PMID

  13. The atypical chemokine receptor D6 contributes to the development of experimental colitis1

    PubMed Central

    Bordon, Yvonne; Hansell, Chris A. H.; Sester, David P; Clarke, Mairi; Mowat, Allan McI.; Nibbs, Robert J. B.

    2009-01-01

    Pro-inflammatory CC chemokines control leukocyte recruitment and function during inflammation by engaging chemokine receptors expressed on circulating leukocytes. The D6 chemokine receptor can bind several of these chemokines but appears unable to couple to signal transduction pathways or direct cell migration. Instead, D6 has been proposed to act as a chemokine scavenger, removing pro-inflammatory chemokines to dampen leukocyte responses. In this report, we have examined the role of D6 in the colon using the dextran sodium sulphate-induced model of colitis. We show that D6 is expressed in the resting colon, predominantly by stromal cells and B cells, and is up-regulated during colitis. Unexpectedly, D6-deficient mice showed reduced susceptibility to colitis and had less pronounced clinical symptoms associated with this model. D6 deletion had no impact on the level of pro-inflammatory CC chemokines released from cultured colon explants, or on the balance of leukocyte subsets recruited to the inflamed colon. However, late in colitis, inflamed D6-deficient colons showed enhanced production of several pro-inflammatory cytokines, including IFNγ and IL-17A, and there was a marked increase in IL-17A-secreting γδ T cells in the lamina propria. Moreover, antibody-mediated neutralisation of IL-17A worsened the clinical symptoms of colitis at these later stages of the response in D6-deficient, but not wild-type, mice. Thus, D6 can contribute to the development of colitis by regulating IL-17A secretion by γδ T cells in the inflamed colon. PMID:19342683

  14. 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

  15. Over-Expression of CD200 Protects Mice from Dextran Sodium Sulfate Induced Colitis

    PubMed Central

    Chen, Zhiqi; Yu, Kai; Zhu, Fang; Gorczynski, Reginald

    2016-01-01

    Background and aim CD200:CD200 receptor (CD200R) interactions lead to potent immunosuppression and inhibition of autoimmune inflammation. We investigated the effect of "knockout"of CD200 or CD200R, or over-expression of CD200, on susceptibility to dextran sodium sulfate (DSS)—induced colitis, a mouse model of inflammatory bowel disease (IBD). Methods Acute or chronic colitis was induced by administration of dextran sodium sulfate (DSS) in four groups of age-matched C57BL/6 female mice: (1) CD200-transgenic mice (CD200tg); (2) wild-type (WT) mice; (3) CD200 receptor 1-deficient (CD200R1KO) mice; and (4) CD200-deficient (CD200KO) mice. The extent of colitis was determined using a histological scoring system. Colon tissues were collected for quantitative RT-PCR and Immunohistochemical staining. Supernatants from colonic explant cultures and mononuclear cells isolated from colonic tissue were used for ELISA. Results CD200KO and CD200R1KO mice showed greater sensitivity to acute colitis than WT mice, with accelerated loss of body weight, significantly higher histological scores, more severe infiltration of macrophages, neutrophils and CD3+ cells, and greater expression of macrophage-derived inflammatory cytokines, whose production was inhibited in vitro (in WT/CD200KO mouse cells) by CD200. In contrast, CD200tg mice showed less sensitivity to DSS compared with WT mice, with attenuation of all of the features seen in other groups. In a chronic colitis model, greater infiltration of Foxp3+ regulatory T (Treg) cells was seen in the colon of CD200tg mice compared to WT mice, and anti-CD25 mAb given to these mice attenuated protection. Conclusions The CD200:CD200R axis plays an immunoregulatory role in control of DSS induced colitis in mice. PMID:26841120

  16. Colitis Promotes Adaptation of an Intestinal Nematode: A Heligmosomoides Polygyrus Mouse Model System

    PubMed Central

    Donskow-Łysoniewska, Katarzyna; Bien, Justyna; Brodaczewska, Klaudia; Krawczak, Katarzyna; Doligalska, Maria

    2013-01-01

    The precise mechanism of the very effective therapeutic effect of gastrointestinal nematodes on some autoimmune diseases is not clearly understood and is currently being intensively investigated. Treatment with living helminths has been initiated to reverse intestinal immune-mediated diseases in humans. However, little attention has been paid to the phenotype of nematodes in the IBD-affected gut and the consequences of nematode adaptation. In the present study, exposure of Heligmosomoides polygyrus larvae to the changed cytokine milieu of the intestine during colitis reduced inflammation in an experimental model of dextran sulphate sodium (DSS)- induced colitis, but increased nematode establishment in the moderate-responder BALB/c mouse strain. We used mass spectrometry in combination with two-dimensional Western blotting to determine changes in protein expression and changes in nematode antigens recognized by IgG1 in mice with colitis. We show that nematode larvae immunogenicity is changed by colitis as soon as 6 days post-infection; IgG1 did not recognize highly conserved proteins Lev-11 (isoform 1 of tropomyosin α1 chain), actin-4 isoform or FTT-2 isoform a (14-3-3 family) protein. These results indicate that changes in the small intestine provoked by colitis directly influence the nematode proteome. The unrecognized proteins seem to be key antigenic epitopes able to induce protective immune responses. The proteome changes were associated with weak immune recognition and increased larval adaptation and worm growth, altered localization in the intestine and increased survival of males but reduced worm fecundity. In this report, the mechanisms influencing nematode survival and the consequences of changed immunogenicity that reflect the immune response at the site colonized by the parasite in mice with colitis are described. The results are relevant to the use of live parasites to ameliorate IBD. PMID:24167594

  17. Antiinflammatory Effect of Phytosterols in Experimental Murine Colitis Model: Prevention, Induction, Remission Study

    PubMed Central

    Aldini, Rita; Micucci, Matteo; Cevenini, Monica; Fato, Romana; Bergamini, Christian; Nanni, Cristina; Cont, Massimiliano; Camborata, Cecilia; Spinozzi, Silvia; Montagnani, Marco; Roda, Giulia; D'Errico-Grigioni, Antonia; Rosini, Francesca; Roda, Aldo; Mazzella, Giuseppe; Chiarini, Alberto; Budriesi, Roberta

    2014-01-01

    Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects. PMID:25268769

  18. 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. PMID:25917208

  19. Effects of ketanserin on experimental colitis in mice and macrophage function

    PubMed Central

    XIAO, JUNHUA; SHAO, LIMEI; SHEN, JIAQING; JIANG, WEILIANG; FENG, YUN; ZHENG, PING; LIU, FEI

    2016-01-01

    Ketanserin is a selective 5-hydroxytryptamine (serotonin)-2A receptor (5-HT2AR) antagonist. Studies have suggested that ketanserin exerts anti-inflammatory effects independent of the baroreflex; however, the mechanisms involved remain unclear. Thus, in the present study, we aimed to evaluate the effects of ketanserin in colitis and the possible underlying mechanisms. The expression of 5-HT2AR was assessed in the colon tissues of patients with inflammatory bowel disease (IBD) and in mice with dextran sodium sulfate (DSS)-induced colitis. The therapeutic potential of ketanserin was investigated in the mice with colitis. In the colon tissue samples from the patients with IBD, a high expression level of 5-HT2AR was observed. Treatment with ketanserin attenuated the progression of experimental colitis in the mice, as indicated by body weight assessment, colon length, histological scores and cytokine release. The colonic macrophages from the ketanserin-treated mice with colitis exhibited a decreased production of inflammatory cytokines, with M2 polarization and impaired migration. The knockdown of 5-HT2AR using siRNA partly abolished the inhibitory effects of ketanserin on the release of pro-inflammatory cytokines in bone marrow derived-macrophages (BMDMs), thus demonstrating that the inhibitory effects of ketanserin on the production of inflammatory cytokines are partly dependent on 5-HT2AR. Ketanserin also inhibited the activation of nuclear factor-κB (NF-κB) in BMDMs. In conclusion, the findings of the present study demonstrate that ketanserin alleviates colitis. Its anti-inflammatory effects may be due to the promotion of the anti-inflammatory function of macrophages through 5-HT2AR/NF-κB. PMID:26865503

  20. Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity.

    PubMed

    Carbonnel, F; Lavergne, A; Lémann, M; Bitoun, A; Valleur, P; Hautefeuille, P; Galian, A; Modigliani, R; Rambaud, J C

    1994-07-01

    Complications that might lead to surgery in severe attacks of ulcerative colitis have been found to be correlated with the depth of colonic ulcerations as measured by pathological examination of colectomy specimens. In order to evaluate the value of colonoscopy for the assessment of colonic ulcerations, we have reviewed the clinical, biological, colonoscopic, and anatomical findings in 85 consecutive patients with attacks of ulcerative colitis involving at least the rectosigmoid and part of the descending colon, seen in our center between 1981 and 1989. All had colonoscopy performed by a senior endoscopist at entry. Extensive deep colonic ulcerations were diagnosed in 46 of them, and moderate endoscopic colitis in 39. No complication related to colonoscopy occurred except for one colonic dilatation. Forty-three of the 46 patients with severe endoscopic colitis were operated upon; 38 of them failed to improve with high-dose corticosteroids and five had a toxic megacolon. Extensive ulcerations reaching at least the circular muscle layer were found at pathological examination of colectomy specimen in 42 of the 43 patients. Conversely, 30 of 39 patients with moderate endoscopic colitis went into clinical remission with medical treatment, and only nine patients needed further surgery because of medical treatment failure. Six of these nine patients underwent another colonoscopy prior to colectomy, and all six showed features of severe endoscopic colitis. Deep ulcerations reaching the circular muscle layer were found at pathological examination in five of these six patients and in one additional patient whose colonoscopy had been performed 21 days before colectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8026269

  1. 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

  2. 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

  3. Fracture risk is increased in Crohn's disease, but not in ulcerative colitis

    PubMed Central

    Vestergaard, P; Krogh, K; Rejnmark, L; Laurberg, S; Mosekilde, L

    2000-01-01

    AIMS—To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis.
METHODS—998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed.
RESULTS—Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0.01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50).
CONCLUSIONS—An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.


Keywords: fracture; Crohn's disease; ulcerative colitis; inflammatory bowel disease; osteoporosis PMID:10644310

  4. 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

  5. [Surgical treatment of toxic megacolon complicating pseudomembranous colitis. Apropos of a case, review of the literature].

    PubMed

    Panis, Y; Hautefeuille, P; Hecht, Y; Le Houelleur, J; Gompel, H

    1992-01-01

    Toxic megacolon complicating pseudomembranous colitis has been rarely observed. Only 36 cases have been previously reported. We present herein a new case report in which pseudomembranous colitis was secondary to prophylactic antibiotherapy with pefloxacin for hip prosthesis. Despite specific oral treatment (against Clostridium difficile) by vancomycin, toxic megacolon required urgent subtotal colectomy with ileostomy and sigmoidostomy. Postoperative course was uneventful. Analysis of the reported cases demonstrates the high overall mortality of the series (32%); the procedure of choice seems to be subtotal colectomy, which removes the septic focus, with a 12% operative mortality rate. PMID:1416759

  6. Ulcerative colitis and neurofibromatosis type 1 with bilateral psoas muscle neurofibromas: a case report

    PubMed Central

    Tavakkoli, Hamid; Asadi, Mehrnaz; Mahzouni, Parvin; Foroozmehr, Abdolali

    2009-01-01

    The most common gastrointestinal involvement in neurofibromatosis is due to tumoral lesions which may present with gastrointestinal bleeding or obstruction. We report a case of concurrent ulcerative colitis and neurofibromatosis. A 39 year-old woman, known case of neurofibromatosis, was admitted to our department with complaint of chronic bloody diarrhea. After thorough clinical examination and paraclinical assessments, including colonoscopy and biopsy, ulcerative colitis was confirmed as the cause of gastrointestinal bleeding. Another rare finding in this patient was bilateral neurofibroma in psoas muscle that was detected on abdominal spiral Computer Tomography scan. PMID:21772893

  7. Composite lymphoma in a patient with ulcerative colitis: a case report.

    PubMed

    Ashrafi, Farzaneh; Kowsari, Farid; Darakhshandeh, Ali; Adibi, Peyman

    2014-10-01

    A 45-year-old female patient with a diagnosis of ulcerative colitis complicated with composite lymphoma in the spleen and para-aortic lymph node presented with a one-month history of malaise, weakness and fatigue. Only mesalamine kept ulcerative colitis under control. In physical examination, splenomegaly was revealed and pancytopenia was obtained from laboratory data. Computed tomography scan revealed para-aortic mediastinal lymphadenopathy with splenomegaly. Splenectomy and excisional biopsy of abdominal lymph node were performed and disease was diagnosed as composite lymphoma, consisting of diffuse large B-cell lymphoma and nodular sclerosing Hodgkin lymphoma. PMID:25774267

  8. Butyrate and glucose metabolism by colonocytes in experimental colitis in mice

    PubMed Central

    Ahmad, M; Krishnan, S; Ramakrishna, B; Mathan, M; Pulimood, A; Murthy, S

    2000-01-01

    BACKGROUND/AIMS—Impaired colonocyte metabolism of butyrate has been implicated in the aetiopathogenesis of ulcerative colitis. Colonocyte butyrate metabolism was investigated in experimental colitis in mice.
METHODS—Colitis was induced in Swiss outbred white mice by oral administration of 4% dextran sulphate sodium (DSS). Colonocytes isolated from colitic and normal control mice were incubated with [14C]butyrate or glucose, and production of 14CO2, as well as of intermediate metabolites (acetoacetate, β-hydroxybutyrate and lactate), was measured. The effect of different substrate concentrations on oxidation was also examined.
RESULTS—Butyrate oxidation (µmol/h per mg protein; mean (SEM)) was significantly reduced in DSS colitis, values on day 7 of DSS administration being 0.177 (0.007) compared with 0.406 (0.035) for control animals (p<0.001). Glucose oxidation (µmol/h per mg protein; mean (SEM)) on day 7 of DSS administration was significantly higher than in controls (0.06 (0.006) v 0.027 (0.004), p<0.001). Production of β-hydroxybutyrate was decreased and production of lactate increased in DSS colitis compared with controls. Increasing butyrate concentration from 10 to 80 mM enhanced oxidation in DSS colitis (0.036 (0.002) to 0.285 (0.040), p<0.001), although it continued to remain lower than in controls. Surface and crypt epithelial cells showed similar ratios of butyrate to glucose oxidation. When 1 mM DSS was added to normal colonocytes in vitro, it did not alter butyrate oxidation. The initial histological lesion of DSS administration was very patchy and involved crypt cells. Abnormal butyrate oxidation became apparent only after six days of DSS administration, at which time histological abnormalities were more widespread.
CONCLUSIONS—Colonocyte metabolism of butyrate, but not of glucose, is impaired in DSS colitis, and may be important in pathophysiology. Histological abnormalities preceded measurable defects in butyrate

  9. Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model

    PubMed Central

    2013-01-01

    Background Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis. N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro. NAC can affect several signaling pathways involving in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and inflammatory response. Therefore, NAC may not only protect against the direct injurious effects of oxidants, but also beneficially alter inflammatory events in colitis. This study was conducted to investigate whether NAC could alleviate the AA-induced colitis in a porcine model. Methods Weaned piglets were used to investigate the effects of NAC on AA-induced colitis. Severity of colitis was evaluated by colon histomorphology measurements, histopathology scores, tissue myeloperoxidase activity, as well as concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon. The protective role of NAC was assessed by measurements of antioxidant status, growth modulator, cell apoptosis, and tight junction proteins. Abundances of caspase-3 and claudin-1 proteins in colonic mucosae were determined by the Western blot method. Epidermal growth factor receptor, amphiregulin, tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4) mRNA levels in colonic mucosae were quantified using the real-time fluorescent quantitative PCR. Results Compared with the control group, AA treatment increased (P < 0.05) the histopathology scores, intraepithelial lymphocyte (IEL) numbers and density in the colon, myeloperoxidase activity, the concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon, while reducing (P < 0.05) goblet cell numbers and the protein/DNA ratio in the colonic mucosa. These adverse effects of AA were partially ameliorated (P < 0.05) by dietary

  10. 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. PMID:18291588

  11. 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

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

    PubMed Central

    Sung, Mi-Kyung; Park, Mi-Young

    2013-01-01

    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. Ipilimumab-induced colitis: experience from a tertiary referral center

    PubMed Central

    O’Connor, Anthony; Marples, Maria; Mulatero, Clive; Hamlin, John; Ford, Alexander C.

    2016-01-01

    Background: Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody used for the treatment of malignant melanoma. It can cause immune-mediated inflammatory adverse events, including diarrhoea and even intestinal perforation or death in clinical trials but there is a dearth of data on postmarketing outcomes. Methods: A total of 546 patients attending for treatment of metastatic melanoma between 1 January 2009 and 31 August 2015 were identified by interrogation of the oncology database. A total of 83 of these patients received ipilimumab. Clinical information was extracted from chart reviews, endoscopy and radiology reports, and prescription data. Results: A total of 83 patients received ipilimumab. Only 19.3% (n = 16) of patients developed a diarrhoeal illness not attributable to other causes. The median grade of diarrhoea among included patients was 2 (range 1–4). In two cases, diarrhoea settled spontaneously without any specific treatment. A total of 87.5% of patients received antidiarrhoeal agents such as loperamide or codeine. These resolved symptoms in all patients with grade 1 diarrhoea. For other treatment, 50% patients received systemic glucocorticosteroids and 31.3% required infliximab. Infliximab resolved symptoms in 100% of cases compared with 50% for systemic glucocorticosteroids. Conclusions: The rate of diarrhoea related to ipilimumab in real-world practice is substantial, but below the range observed in data from RCTs. Grade 1 colitis can usually be managed symptomatically, without recourse to stopping ipilimumab. When diarrhoea was grade 2 or above, results from glucocorticosteroids use proved disappointing; but infliximab has been shown to work well. Further research is required into the earlier use of infliximab as an effective treatment for ipilimumab-induced diarrhoea. PMID:27366214

  14. Low prevalence of Blastocystis sp. in active ulcerative colitis patients.

    PubMed

    Rossen, N G; Bart, A; Verhaar, N; van Nood, E; Kootte, R; de Groot, P F; D'Haens, G R; Ponsioen, C Y; van Gool, T

    2015-05-01

    Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls. PMID:25680316

  15. 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

  16. Enterohepatic Helicobacter in Ulcerative Colitis: Potential Pathogenic Entities?

    PubMed Central

    Thomson, John M.; Hansen, Richard; Berry, Susan H.; Hope, Mairi E.; Murray, Graeme I.; Mukhopadhya, Indrani; McLean, Mairi H.; Shen, Zeli; Fox, James G.; El-Omar, Emad; Hold, Georgina L.

    2011-01-01

    Background Changes in bacterial populations termed “dysbiosis” are thought central to ulcerative colitis (UC) pathogenesis. In particular, the possibility that novel Helicobacter organisms play a role in human UC has been debated but not comprehensively investigated. The aim of this study was to develop a molecular approach to investigate the presence of Helicobacter organisms in adults with and without UC. Methodology/Principal Findings A dual molecular approach to detect Helicobacter was developed. Oligonucleotide probes against the genus Helicobacter were designed and optimised alongside a validation of published H. pylori probes. A comprehensive evaluation of Helicobacter genus and H. pylori PCR primers was also undertaken. The combined approach was then assessed in a range of gastrointestinal samples prior to assessment of a UC cohort. Archival colonic samples were available from 106 individuals for FISH analysis (57 with UC and 49 non-IBD controls). A further 118 individuals were collected prospectively for dual FISH and PCR analysis (86 UC and 32 non-IBD controls). An additional 27 non-IBD controls were available for PCR analysis. All Helicobacter PCR-positive samples were sequenced. The association between Helicobacter and each study group was statistically analysed using the Pearson Chi Squared 2 tailed test. Helicobacter genus PCR positivity was significantly higher in UC than controls (32 of 77 versus 11 of 59, p = 0.004). Sequence analysis indicated enterohepatic Helicobacter species prevalence was significantly higher in the UC group compared to the control group (30 of 77 versus 2 of 59, p<0.0001). PCR and FISH results were concordant in 74 (67.9%) of subjects. The majority of discordant results were attributable to a higher positivity rate with FISH than PCR. Conclusions/Significance Helicobacter organisms warrant consideration as potential pathogenic entities in UC. Isolation of these organisms from colonic tissue is needed to enable

  17. Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis

    PubMed Central

    Giriş, M; Depboylu, B; Doğru-Abbasoğlu, S; Erbil, Y; Olgaç, V; Alış, H; Aykaç-Toker, G; Uysal, M

    2008-01-01

    Ulcerative colitis (UC) is a multi-factorial inflammatory disease of the colon and rectum. The present study was undertaken to investigate the effect of taurine, an anti-oxidant amino acid, on oxidative stress and the expression of apoptosis-related proteins, pro-apoptotic Bax and anti-apoptotic B cell lymphoma-2 (Bcl-2) in colon tissue in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Rats received taurine (1·5% w/v) in drinking water for 15 days before and 15 days after administration of TNBS solution. Then, colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and Bax and Bcl-2 expression were measured. TNBS-induced colitis caused significantly increased MPO activity and MDA levels and decreased GSH levels in colon tissue compared to controls. Increase in Bax expression and decrease in Bcl-2 expression were detected in colon of rats with TNBS-induced colitis. Taurine treatment was associated with amelioration in macroscopic and microscopic colitis scores, decreased colonic MPO activity and MDA levels and increased GSH levels in TNBS-induced colitis. In addition, taurine reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of rats with TNBS-induced colitis. The results of this study show that taurine administration may exert beneficial effects in UC by decreasing inflammatory reactions, oxidative stress and apoptosis. PMID:18241224

  18. Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process.

    PubMed Central

    Winslet, M C; Allan, A; Poxon, V; Youngs, D; Keighley, M R

    1994-01-01

    The high incidence of clinical remission after faecal diversion for Crohn's colitis suggests the faecal stream may play a part in the inflammatory mechanism. The effect of faecal diversion (n = 22) and restoration of intestinal continuity (n = 10) was assessed in patients with Crohn's colitis and compared with controls. Faecal diversion produced significant improvement in the disease activity index mean (SEM) (before 176 (9); after 114 (9), p < 0.01) and serum albumin concentrations (before 33 (3.0); after 38 (3.0), p < 0.05) in all patients with Crohn's colitis. The crypt cell production rate (CCPR) was maintained after faecal diversion for Crohn's colitis but fell in the control group (before = 3.6 (0.8)), at two (1.4 (0.4), p < 0.02), and six weeks (1.6 (0.4), p < 0.05). Mucosal glucosamine synthetase activity, reflecting glycoprotein synthesis, was significantly lower in patients with Crohn's colitis (analysis of variance p < 0.05) after diversion but was maintained in the control group. Restoration of intestinal continuity failed to produce reciprocal changes. The sustained cellular proliferation and fall in glycoprotein synthesis in Crohn's colitis after faecal diversion may represent the end of an exaggerated protective response and regenerative hyperplasia after exclusion of the faecal stream. This study suggests the faecal stream may participate in the inflammatory process in Crohn's colitis. The underlying mechanism is unknown. PMID:8307475

  19. 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.

  20. 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

    2015-01-01

    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. PMID:26013555

  1. 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

  2. Visceral pain perception is determined by the duration of colitis and associated neuropeptide expression in the mouse

    PubMed Central

    Verma‐Gandhu, Monica; Verdu, Elena F; Bercik, Premysl; Blennerhassett, Patricia A; Al‐Mutawaly, Nafia; Ghia, Jean‐Eric; Collins, Stephen M

    2007-01-01

    Background Even though inflammation is a traditional tool for the induction of hyperalgesia in many tissues, recent observations suggest that not all inflammatory processes produce this change. Tolerance to colorectal distension (CRD) is reduced in patients with acute ulcerative colitis but is increased in patients with chronic inflammatory bowel disease. This suggests that the nature of the inflammatory infiltrate influences visceral perception. Aim To test this hypothesis by assessing responses to CRD in mice with mild, acute or chronic colitis. Methods CRD responses were measured in mice with mild non‐specific colitis, and dextran sodium sulphate (DSS)‐induced acute and chronic colitis. Responses were compared with tissue infiltrate and damage, interleukin (IL)1β and myeloperoxidase (MPO) activity and substance P, β‐endorphin and μ opioid receptor (MOR) expression. Results Mild and acute colitis were associated with increased responsiveness to CRD. In contrast, CRD responses were not increased in mice with chronic colitis and this difference was not due to altered colonic wall compliance. MPO and IL1β levels were greater in acute than in chronic colitis. Larger increases in tissue substance P were seen in acute than in chronic DSS, whereas CD4 T cells, β‐endorphin and MOR expression were evident only in chronic colitis. An inverse correlation was seen between substance P and MOR in these tissues. Conclusions Acute colitis increased responsiveness to CRD and is accompanied by an acute inflammatory infiltrate and increased tissue substance P. Chronic DSS is accompanied by an increase in β‐endorphin and MOR expression, and CD4 T cells, but no change in compliance or CRD responses. We conclude that acute inflammation generates hyperalgesia, whereas chronic inflammation involves infiltration by lymphocytes accompanied by MOR and β‐endorphin up regulation, and this provides an antinociceptive input that restores normal visceral perception. PMID

  3. The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis

    PubMed Central

    Pitcher, M; Beatty, E; Cummings, J

    2000-01-01

    BACKGROUND—Butyrate oxidation within the colonocyte is selectively inhibited by hydrogen sulphide, reproducing the metabolic lesion observed in active ulcerative colitis.
AIMS—To study generation of hydrogen sulphide by sulphate reducing bacteria (SRB) and the effects of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis in order to identify a role of this noxious agent in pathogenesis.
PATIENTS—Fresh faeces were obtained from 37 patients with ulcerative colitis (23 with active disease) and 16 healthy controls.
METHODS—SRB were enumerated from fresh faecal slurries and measurements made of sulphate reducing activity, and sulphate and hydrogen sulphide concentrations. The effect of 5-ASA on hydrogen sulphide production was studied in vitro.
RESULTS—All controls and patients with active ulcerative colitis carried SRB and total viable counts were significantly related to the clinical severity grade. SRB were of two distinct types: rapidly growing strains (desulfovibrios) which showed high sulphate reduction rates, present in 30% of patients with ulcerative colitis and 44% of controls; and slow growing strains which had little activity. In vitro, 5-ASA inhibited sulphide production in a dose dependent manner; in patients with ulcerative colitis not on these drugs faecal sulphide was significantly higher than in controls (0.55 versus 0.25 mM, p=0.027).
CONCLUSIONS—Counts and carriage rates of SRB in faeces of patients with ulcerative colitis are not significantly different from those in controls. SRB metabolism is not uniform between strains and alternative sources of hydrogen sulphide production exist in the colonic lumen which may be similarly inhibited by 5-ASA. The evidence for hydrogen sulphide as a metabolic toxin in ulcerative colitis remains circumstantial.


Keywords: colitis; sulphate; sulphide; bacteria; fermentation; salicylate PMID:10601057

  4. Anti-inflammatory effects of Inonotus obliquus in colitis induced by dextran sodium sulfate.

    PubMed

    Choi, Se Young; Hur, Sun Jin; An, Chi Sun; Jeon, Yun Hui; Jeoung, Young Jun; Bak, Jong Phil; Lim, Beong Ou

    2010-01-01

    A total of 28 male BALB/c mice (average weight 20.7 +/- 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-alpha and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-alpha, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells. PMID:20300439

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

    PubMed

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

    2015-11-15

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

  6. 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

  7. The effect of methylsulfonylmethane on the experimental colitis in the rat.

    PubMed

    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-α and IL-1β) 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-1β, 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. PMID:21463646

  8. Metabolomics Reveals that Hepatic Stearoyl-CoA Desaturase 1 Downregulation Exacerbates Inflammation and Acute Colitis

    PubMed Central

    Chen, Chi; Shah, Yatrik M.; Morimura, Keiichirou; Krausz, Kristopher W.; Miyazaki, Makoto; Richardson, Terrilyn A.; Morgan, Edward T.; Ntambi, James M.; Idle, Jeffrey R.; Gonzalez, Frank J.

    2008-01-01

    SUMMARY To investigate the pathogenic mechanism of ulcerative colitis, a dextran sulfate sodium (DSS)-induced acute colitis model was examined by serum metabolomic analysis. Higher levels of stearoyl lysophosphatidylcholine and lower levels of oleoyl lysophosphatidylcholine in DSS-treated mice compared to controls led to the identification of DSS-elicited inhibition of stearoyl-CoA desaturase 1 (SCD1) expression in liver. This decrease occurred prior to the symptoms of acute colitis and was well correlated with elevated expression of proinflammatory cytokines. Furthermore, Citrobacter rodentium-induced colitis and lipopolysaccharide treatment also suppressed SCD1 expression in liver. Scd1 null mice were more susceptible to DSS treatment than wild-type mice, while oleic acid feeding and in vivo SCD1 rescue with SCD1 adenovirus alleviated the DSS-induced phenotype. This study reveals that inhibition of SCD1-mediated oleic acid biogenesis exacerbates proinflammatory responses to exogenous challenges, suggesting that SCD1 and its related lipid species may serve as potential targets for intervention or treatment of inflammatory diseases. PMID:18249173

  9. Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage

    PubMed Central

    Vargas Robles, Hilda; Citalán Madrid, Alí Francisco; García Ponce, Alexander; Silva Olivares, Angelica; Shibayama, Mineko; Betanzos, Abigail; Del Valle Mondragón, Leonardo; Nava, Porfirio; Schnoor, Michael

    2016-01-01

    Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD. PMID:26881044

  10. 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. PMID:23665423

  11. 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...

  12. 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

  13. A decision analysis of surveillance for colorectal cancer in ulcerative colitis

    PubMed Central

    Delco, F; Sonnenberg, A

    2000-01-01

    BACKGROUND—Patients with long standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer.
AIMS—To assess the feasibility of surveillance colonoscopy in preventing death from colorectal cancer.
PATIENTS—A hypothetical cohort of patients with chronic ulcerative colitis.
METHODS—The benefits of life years saved were weighted against the costs of biannual colonoscopy and proctocolectomy, and the terminal care of patients dying from colorectal cancer. Two separate Markov processes were modelled to compare the cost-benefit relation in patients with or without surveillance. The cumulative probability of developing colorectal cancer served as a threshold to determine which of the two management strategies is associated with a larger net benefit.
RESULTS—If the cumulative probability of colorectal cancer exceeds a threshold value of 27%, surveillance becomes more beneficial than no surveillance. The threshold is only slightly smaller than the actual cumulative cancer rate of 30%. Variations of the assumptions built into the model can raise the threshold above or lower it far below the actual rate. If several of the assumptions are varied jointly, even small changes can lead to extreme threshold values.
CONCLUSIONS—It is not possible to prove that frequent colonoscopies scheduled at regular intervals are an effective means to manage the increased risk of colorectal cancer associated with ulcerative colitis.


Keywords: cancer screening; colorectal cancer; health economics; medical decision analysis; surveillance colonoscopy; ulcerative colitis PMID:10716679

  14. Anti-inflammatory effect of taurocholate on TNBS-induced ulcerative colitis in mice.

    PubMed

    Yang, Yang; He, Jiao; Suo, Yuan; Lv, Le; Wang, Jingjing; Huo, Chuanchuan; Zheng, Zongwei; Wang, Ziye; Li, Jing; Sun, Wenji; Zhang, Yongmin

    2016-07-01

    Taurocholate is a natural conjugated bile acid. The aim of this study was to evaluate the anti-inflammatory effect of taurocholate in TNBS-induced ulcerative colitis in mice. The colitis were induced by rectal administration of TNBS. After 24h, the experimental animals were treated with sulfasalazine (SASP, 500mg/kg/day) and taurocholate (20, 40 and 60mg/kg) for 7 consecutive days. The anti-inflammatory effects of taurocholate for colitis were assessed by body weight, colonic weight and length, macroscopic scores, and histopathological examinations. In addition, the colonic tissue levels of myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN-γ) and tumour necrosis factor-α (TNF-α) were also determined to assess the effect of taurocholate. Compared with the model group, treatment with taurocholate (20, 40 and 60mg/kg) significantly inhibited the body weight loss, improved colonic weight and length, and decreased macroscopic and histopathological scores. Furthermore, the activity accumulation of MPO and the colonic tissue levels of IL-1β, IFN-γ and TNF-α were also decreased by administration of taurocholate. All the findings of this study suggested that taurocholate has the anti-inflammatory effect in ulcerative colitis in mice and indicated it as a good candidate to treat inflammatory bowel disease. PMID:27261622

  15. 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

  16. 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

  17. Herpes simplex virus (HSV) colitis in a bone marrow transplant recipient.

    PubMed

    Naik, H R; Chandrasekar, P H

    1996-02-01

    Herpes simplex virus (HSV) infections are common in bone marrow transplantation patients. Unusual sites may be involved, however colonic disease with HSV is rare. We report a successfully treated case of colitis due to HSV, cytomegalovirus, Clostridium difficile and graft-versus-host disease in an allogeneic marrow recipient. PMID:8640181

  18. 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

  19. 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

  20. 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. PMID:27471608

  1. Anti-Inflammatory Effects of Inonotus obliquus in Colitis Induced by Dextran Sodium Sulfate

    PubMed Central

    Choi, Se Young; Hur, Sun Jin; An, Chi Sun; Jeon, Yun Hui; Jeoung, Young Jun; Bak, Jong Phil; Lim, Beong Ou

    2010-01-01

    A total of 28 male BALB/c mice (average weight 20.7 ± 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-α and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-α, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells. PMID:20300439

  2. High-resolution microbiota flow cytometry reveals dynamic colitis-associated changes in fecal bacterial composition.

    PubMed

    Zimmermann, Jakob; Hübschmann, Thomas; Schattenberg, Florian; Schumann, Joachim; Durek, Pawel; Riedel, René; Friedrich, Marie; Glauben, Rainer; Siegmund, Britta; Radbruch, Andreas; Müller, Susann; Chang, Hyun-Dong

    2016-05-01

    Using high-resolution flow cytometry of bacterial shape (forward scatter) and DNA content (DAPI staining), we detected dramatic differences in the fecal microbiota composition during murine colitis that were validated using 16S rDNA sequencing. This innovative method provides a fast and inexpensive tool to interrogate the microbiota on the single-cell level. PMID:26909672

  3. Alleviation of Antioxidant Defense System by Ozonized Olive Oil in DNBS-Induced Colitis in Rats

    PubMed Central

    Bayoumi, Fatehia A.; Ahmed, Naglaa G.

    2014-01-01

    The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO) in 2,4-dinitrobenzene sulphuric acid (DNBS) induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase “SOD,” glutathione peroxidase “GSH-Px,” and catalase “CAT”) in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO) at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes. PMID:25276059

  4. 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

  5. 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

  6. 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

  7. 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

  8. Inflammasome activation has an important role in the development of spontaneous colitis.

    PubMed

    Zhang, J; Fu, S; Sun, S; Li, Z; Guo, B

    2014-09-01

    Inflammatory bowel disease (IBD) is characterized for dysregulated intestinal inflammation. Conflicting reports have shown that activation of inflammasome could promote or decrease intestinal inflammation in an acute colitis model, whereas the involvement of inflammasome activation in chronic colitis is poorly understood. In this study, we investigated the role of inflammasome activation in the development of chronic intestinal inflammation by utilizing interleukin-10 (IL-10) knockout (KO) mouse as an animal model, which develops chronic colitis resembling human IBD. We demonstrate the causative link between inflammasome activation and the development of chronic intestinal inflammation. Our results show that mature IL-1β protein levels were significantly increased in all colon sections from IL-10-deficient mice compared with that of wild-type mice. We found that inhibition of inflammasome activities with IL-1 receptor antagonist or caspase-1 inhibitors suppressed IL-1β and IL-17 production from inflamed colon explants. Furthermore, blocking inflammasome activation with caspase-1 inhibitor in vivo significantly ameliorated the spontaneous colitis in IL-10 KO mice. Taken together, these observations demonstrate that inflammasome activation promotes the development of chronic intestinal inflammation. PMID:24472848

  9. Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review.

    PubMed

    Nidhi; Rashid, Muzamil; Kaur, Veerpal; Hallan, Supandeep Singh; Sharma, Saurabh; Mishra, Neeraj

    2016-07-01

    Ulcerative colitis is the chronic relapsing multifactorial gastrointestinal inflammatory bowel disease, which is characterized by bloody or mucus diarrhea, tenesmus, bowel dystension, anemia. The annual incidence of ulcerative colitis in Asia, North America and Europe was found to be 6.3, 19.2 and 24.3 per 100,000 person-years. The major challenge in the treatment of ulcerative colitis is appropriate local targeting and drug related side-effects. To overcome these challenges, microparticulate systems seem to be a promising approach for controlled and sustained drug release after oral administration. The main goal of this article is to explore the role of microparticles in ulcerative colitis for the appropriate targeting of drugs to colon. There are different approaches which have been studied over the last decade, including prodrugs, polymeric approach, time released system, pH sensitive system, which show the site specific drug delivery to colon. Among these approaches, microparticulate drug delivery system has been gaining an immense importance for local targeting of drug to colon at a controlled and sustained rate. Combined approaches such as pH dependent and time dependent system provide the maximum release of drug into colon via oral route. This article embraces briefly about pathophysiology, challenges and polymeric approaches mainly multiparticulate systems for site specific drug delivery to colon in sustained and controlled manner so that drug related side-effects by reducing dosage frequency can be minimized. PMID:27330377

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication.

    PubMed

    Trifan, Anca; Girleanu, Irina; Cojocariu, Camelia; Sfarti, Catalin; Singeap, Ana Maria; Dorobat, Carmen; Grigore, Lucia; Stanciu, Carol

    2013-11-14

    Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of world's population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy. PMID:24259981

  18. Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

    PubMed Central

    Trifan, Anca; Girleanu, Irina; Cojocariu, Camelia; Sfarti, Catalin; Singeap, Ana Maria; Dorobat, Carmen; Grigore, Lucia; Stanciu, Carol

    2013-01-01

    Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of world’s population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy. PMID:24259981

  19. Alleviation of antioxidant defense system by ozonized olive oil in DNBS-induced colitis in rats.

    PubMed

    Abu-Gharbieh, Eman; Bayoumi, Fatehia A; Ahmed, Naglaa G

    2014-01-01

    The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO) in 2,4-dinitrobenzene sulphuric acid (DNBS) induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase "SOD," glutathione peroxidase "GSH-Px," and catalase "CAT") in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO) at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes. PMID:25276059

  20. Effect of sophoridine on dextran sulfate sodium-induced colitis in C57BL/6 mice.

    PubMed

    Zhao, Wen-Chang; Song, Li-Jun; Deng, Hong-Zhu

    2010-11-01

    Sophoridine (SRI), one of the quinolizidine alkaloids, is a new anticancer drug with noticeable antitumor action and lower toxicity. To our knowledge, there is no report about its effect on colitis. Repeated colitis was induced by administration of four cycles of 4% DSS. The severity of colitis was assessed on the basis of clinical signs, colon length and histology scores. Moreover, cecum secretory immunoglobulin A (sIgA) and plasma haptoglobin (HP) were analyzed by enzyme-linked immunosorbent assay and ICAM-1, and macrophage migration inhibitory factor (MIF) gene expression was analyzed by quantitative reverse transcriptase real-time polymerase chain reaction using SYBR Green I. SRI administration significantly attenuated the damage and caused substantial reduction of the rise in plasma HP, and maintained the level of cecum sIgA. SRI inhibited the ICAM-1 gene expression and had no effect on MIF gene expression. In conclusion, for the first time, the activity of SRI on DSS-induced colitis mice was investigated, which suggests that SRI could be an attractive therapeutic option in the treatment of inflammatory bowel disease. PMID:21061213

  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. Delayed puberty and response to testosterone in a rat model of colitis.

    PubMed

    Azooz, O G; Farthing, M J; Savage, M O; Ballinger, A B

    2001-11-01

    Delayed puberty is a frequent complication of inflammatory bowel disease. The precise etiological mechanisms are not known. In this study, we wanted to determine the relative contribution of undernutrition and inflammation to delayed puberty and the effect of inflammation on the reproductive axis. Puberty was assessed in rats with 2,4,6-trinitrobenzenesulfonic acid induced-colitis, healthy controls, and animals pair fed to match the food intake of the colitic group. The response to testosterone administration was assessed in colitic rats. We found that induction of colitis was associated with hypophagia and reduced weight gain, and undernutrition in healthy females (i.e., pair fed) resulted in a delay in the onset (by 4.8 days, P < 0.001) and progression of puberty (normal estrous cycles in 42%, P = 0.04) compared with controls. However, puberty was further delayed in the colitic group (1.4 days after pair fed) with the absence of normal estrous cycling in all rats. In males, the onset of puberty was also delayed, and weights of accessory sex organs were reduced compared with pair-fed controls. Plasma testosterone concentrations were low, and gonadotropin concentrations were normal in colitic rats. Testosterone treatment normalized puberty in male rats with colitis. In conclusion, in rats with experimental colitis, inflammation appears to potentiate the effect of undernutrition on puberty. The weights of secondary sex organs and the onset of puberty were normalized by testosterone treatment. PMID:11641119

  3. 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

  4. Morphological Changes in Mesenteric Lymph Nodes and Lymphocyte Subpopulation Composition in Experimental Ulcerative Colitis.

    PubMed

    Postovalova, E A; Khochansky, D N; Zolotova, N A; Gao, Yu; Makarova, O V; Dobrynina, M T

    2016-04-01

    Morphological changes in the mesenteric lymph nodes of male C57Bl/6 mice and subpopulation composition of lymphocytes in these nodes were studied in experimental acute and chronic ulcerative colitis induced by sodium dextran sulfate. Acute and chronic ulcerative colitis was associated with the development of reactive changes in the mesenteric lymph nodes. These changes were of mixed type and were characterized by follicular hyperplasia and sinus reaction. The content of CD19(+) B cells in the mesenteric lymph nodes decreased in acute ulcerative colitis, while the content of CD3(+)CD8(+) cytotoxic T cells increased, which presumably reflected activation of Th1 reactions. The increase in the count of CD4(+)CD25(+)FOXP3(+) regulatory T cells and CD3(+)CD8(+) cytotoxic T cells was due to intensive migration of lymphocytes from the thymus and the colonic compartment of the local immune system. Chronic ulcerative colitis was associated with higher levels of CD19(+) B cells and CD3(+)CD4(+) T helper cells in the mesenteric lymph nodes, which was characteristic of adoptive immunity reactions and chronization of the inflammatory process. PMID:27165070

  5. 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

    2016-01-01

    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

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

    PubMed

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

    2016-04-01

    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

  7. MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function.

    PubMed

    Brauer, R; Tureckova, J; Kanchev, I; Khoylou, M; Skarda, J; Prochazka, J; Spoutil, F; Beck, I M; Zbodakova, O; Kasparek, P; Korinek, V; Chalupsky, K; Karhu, T; Herzig, K-H; Hajduch, M; Gregor, M; Sedlacek, R

    2016-07-01

    Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis. PMID:26555704

  8. 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...

  9. 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

  10. A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis.

    PubMed

    Akagi, Kazuko; Kawai, Toshinao; Watanabe, Nobuyuki; Yokoyama, Midori; Arai, Katsuhiro; Harayama, Shizuko; Oana, Shinji; Onodera, Masafumi

    2014-04-01

    Although macrophage activation syndrome (MAS) develops in some patients with chronic granulomatous disease (CGD), all of the reported cases have been associated with pathogenic microbial infections. We report a 2-year-old boy with CGD-associated colitis who suffered from MAS without any clinical signs of a microbial infection. He was treated with 1 course of methylprednisolone pulse therapy and the clinical symptoms improved; however, the colitis was difficult to control even with immunosuppressive drugs, and he eventually required hematopoietic stem cell transplantation 1 year after the onset of MAS. It is likely that MAS develops in patients with CGD colitis independent of microbial infections. PMID:23652865

  11. A case if infant botulism due to neurotoxigenic Clostridium butyricum type E associated with Clostridium difficile colitis.

    PubMed

    Fenicia, L; Da Dalt, L; Anniballi, F; Franciosa, G; Zanconato, S; Aureli, P

    2002-10-01

    Reported here is the sixth case of intestinal toxemia botulism caused by Clostridium butyricum type E in Italy since 1984. In this case, the patient was concomitantly affected with colitis due to Clostridium difficile toxin. A review of previously reported cases revealed that some of these patients may also have had intestinal toxemia botulism associated with Clostridium difficile colitis, based on the reported symptoms. Given that this association has been shown to exist not only in Italy but also in the USA, it is recommended that individuals with intestinal botulism and symptoms of colitis undergo testing for Clostridium difficile and its toxins in fecal samples. PMID:12479171

  12. A lipidomics investigation into the intervention of celastrol in experimental colitis.

    PubMed

    Wang, Renping; Gu, Xueqin; Dai, Weiquan; Ye, Jun; Lu, Feng; Chai, Yifeng; Fan, Guorong; Gonzalez, Frank J; Duan, Gengli; Qi, Yunpeng

    2016-04-26

    Celastrol is well known for its anti-inflammatory and anti-cancer effects. In this study, the efficacy of celastrol against dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice was established and the mechanism was investigated using lipidomics. Celastrol treatment significantly alleviated DSS-induced colitis in mice, as revealed by the body weight, colon length, scores of rectal bleeding and diarrhea, serum TNF-α level, and histological analysis results. Lipidomics analysis based on UPLC/MS revealed characteristic changes in the metabolic profiles of the colitis mice, with altered levels of lipid markers associated with IBD, including LPC18 : 0, LPC18 : 1, LPC18 : 2, sphingomyelin (SM), and increased LPC18 : 0/LPC18 : 1 and LPC18 : 0/LPC18 : 2 ratios. For the celastrol-treated colitis mice, however, levels of the above lipid markers were restored, together with recovered saturated LPC/unsaturated LPC ratios. Accordingly, using GC-MS analysis, increased stearic acid (C18 : 0)/oleic acid (C18 : 1) and stearic acid (C18 : 0)/linoleic acid (C18 : 2) ratios were observed in colitis mice, which were later recovered after celastrol treatment. Quantitative real-time PCR analysis revealed that the liver expression of stearoyl-coenzyme A desaturase 1 (SCD1), the key enzyme controlling the desaturation of saturated fatty acid, was dramatically inhibited in IBD mice, and was obviously recovered after celastrol treatment. These results suggest that the increased saturated LPC/unsaturated LPC (and saturated fatty acid/unsaturated fatty acid) ratios associated with SCD1 down-regulation could be regarded as biomarkers of colitis, and celastrol alleviates DSS-induced colitis partially via up-regulation of SCD1, restoring the altered balance between stearic acid- and oleic acid-derived lipid species, which plays an important role in alleviating colitis. In all, this study provided the scientific basis for further

  13. Effects of trimetazidine in ethanol- and acetic acid-induced colitis: oxidant/anti-oxidant status.

    PubMed

    Girgin; Karaoglu; Tüzün; Erkus; Ozütemiz; Dinçer; Batur; Tanyalçin

    1999-11-01

    There is overwhelming evidence in favour of a significant role of reactive oxygen metabolites (ROM) in the pathophysiology of inflammatory bowel disease (IBD) in man and in experimental animal models. This study was undertaken to investigate the possible protective effects of pretreatment with trimetazidine (TMZ) on the oxidant-anti-oxidant balance in ethanol- and acetic acid-induced colonic damage in rats. TMZ was chosen because of its various cytoprotective features (preserving cellular ATP levels, limiting intracellular acidosis and limiting inorganic phosphate, Na(+) and Ca(2+) accumulation) and anti-oxy characteristics which were previously reported. A total of 80 rats were randomized into eight major groups each consisting of 10 animals. Animals in groups 1, 2 and 3 served as models of ethanol-induced colitis (0.25 ml of 30% (v/v) ethanol), while group 4 served as their control. Animals in groups 5, 6 and 7 served as models of acetic acid-induced colitis (1 ml of 4% (v/v) acetic acid), while group 8 served as their control. TMZ was administered 5 mg/kg by intrarectal (i.r.) and intraperitoneal (i.p.) routes to groups 1, 2, 5 and 6. Intraperitoneal administration of TMZ was used in order to evaluate its systemic effect while i.r. administration was used to determine its local effect. After decapitation, colon mucosa samples were obtained and evaluated macroscopically and microscopically. Myeloperoxidase (MPO) activities as markers for inflammation, malondialdehyde (MDA) levels as markers for oxidant stress and reduced glutathione (GSH) and oxidized glutathione (GSSG) levels as markers for anti-oxidant status were determined. Acute colitis was observed in macroscopic and microscopic evaluation in ethanol- and acetic acid-administered groups compared with controls (P = 0.000). The macroscopic and microscopic scores in colitis groups were correlated with MPO activities (r = 0.5365, P = 0.000 and r = 0.5499, P = 0.000, respectively). MDA

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

    PubMed Central

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

    2015-01-01

    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

  15. 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

  16. Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis.

    PubMed

    Linden, David R

    2012-11-01

    Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during "acute" inflammation. Hyperexcitability persisted at 6 days post-TNBS during "chronic" inflammation, as well as at 56 days post-TNBS when colitis had resolved. In contrast, there was only a modest decrease in the current required to elicit an action potential at 24 h after acetic acid administration. Vasomotor neurons from inflamed preparations exhibited normal excitability. The excitatory effects of XE-991, a blocker of the channel that contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of the channel that contributes to the A-type potassium current, were unchanged in TNBS-inflamed preparations, suggesting that these currents did not contribute to hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused tonic visceromotor neurons to accommodate to sustained current pulses, regardless of the inflammatory state of the preparation, and restored a normal rheobase in neurons from TNBS-inflamed preparations but did not alter the rheobase of control preparations, suggesting that enhanced activity of voltage-gated sodium channels may contribute to colitis-induced hyperexcitability. Collectively, these data indicate that enhanced sympathetic drive as a result of hyperexcitable visceromotor neurons may contribute to small bowel dysfunction during colitis. PMID:22961805

  17. Use of bacitracin in the prevention and treatment of experimentally-induced idiopathic colitis in horses.

    PubMed Central

    Staempfli, H R; Prescott, J F; Carman, R J; McCutcheon, L J

    1992-01-01

    Ten healthy ponies from a single herd were found by repeated fecal culture to be free of Salmonella species and Clostridium cadaveris. In a preliminary study, four ponies administered a single oral dose of 10 mg/kg lincomycin did not develop idiopathic colitis when the drug was administered alone. Four other ponies were administered 10 mg/kg lincomycin by stomach tube together with 0.45 L of colonic content from a horse with idiopathic colitis induced earlier by lincomycin alone. Two of the four ponies were treated with 25 g oral zinc bacitracin premix (110 g/kg active ingredient) 24 h later. Forty-two hours after inoculation the two untreated ponies had severe signs of idiopathic colitis and were euthanized. Postmortem findings were typical of idiopathic colitis. The two treated ponies had milder illness but the more severely affected was also euthanized; the other was retreated at 42 h with bacitracin pre-mix and again 12 h later. Its illness and diarrhea resolved over the next 24 h. Clostridium cadaveris was isolated in large numbers from the cecum of the euthanized ponies and their cecal content contained mouse lethal and guinea pig dermonecrotic, but not cytotoxic, activity. Enterotoxins of Clostridium perfringens and Clostridium difficile could not be demonstrated. No toxin could be demonstrated in culture supernatants of C. cadaveris or in supernatants of cecal contents treated with ethanol prior to culturing in anaerobically incubated broth. No Salmonella spp. were isolated. A further two ponies were administered 10 mg/kg lincomycin orally with 0.45 L colonic content from a horse with idiopathic colitis, as described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1423060

  18. 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

  19. 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

  20. 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

  1. Specific probiotic dietary supplementation leads to different effects during remission and relapse in murine chronic colitis.

    PubMed

    Zheng, B; van Bergenhenegouwen, J; van de Kant, H J G; Folkerts, G; Garssen, J; Vos, A P; Morgan, M E; Kraneveld, A D

    2016-01-01

    Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-induced bloody diarrhoea during the resolution phase. However, a contradictory effect by both probiotic strains on the faecal condition was found after re-induction of colitis. The worsening of the faecal condition was accompanied by a reduced number of neutrophils and increased expression of interferon-γ in the colons of DSS-treated mice. Furthermore, an increased expression of TLR2, TLR6 and pro-inflammatory markers including chemokine (C-C motif) ligand 2, interleukin (IL)-1β, tumour necrosis factor α and IL-6 was found in DSS-treated mice with L. rhamnosus supplementation. These results indicate that therapeutic administration of specific probiotics might be beneficial during the resolution phase of colitis. However, caution should be taken as specific probiotic treatments reduce neutrophil influx, which may be the reason of exacerbation of chronic colitis. PMID:26645352

  2. Antagonism of protease-activated receptor 2 protects against experimental colitis.

    PubMed

    Lohman, Rink-Jan; Cotterell, Adam J; Suen, Jacky; Liu, Ligong; Do, Anh T; Vesey, David A; Fairlie, David P

    2012-02-01

    Many trypsin-like serine proteases such as β-tryptase are involved in the pathogenesis of colitis and inflammatory bowel diseases. Inhibitors of individual proteases show limited efficacy in treating such conditions, but also probably disrupt digestive and defensive functions of proteases. Here, we investigate whether masking their common target, protease-activated receptor 2 (PAR2), is an effective therapeutic strategy for treating acute and chronic experimental colitis in rats. A novel PAR2 antagonist (5-isoxazoyl-Cha-Ile-spiro[indene-1,4'-piperidine]; GB88) was evaluated for the blockade of intracellular calcium release in colonocytes and anti-inflammatory activity in acute (PAR2 agonist-induced) versus chronic [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] models of colitis in Wistar rats. Disease progression (disease activity index, weight loss, and mortality) and postmortem colonic histopathology (inflammation, bowel wall thickness, and myeloperoxidase) were measured. PAR2 and tryptase colocalization were investigated by using immunohistochemistry. GB88 was a more potent antagonist of PAR2 activation in colonocytes than another reported compound, N¹-3-methylbutyryl-N⁴-6-aminohexanoyl-piperazine (ENMD-1068) (IC₅₀ 8 μM versus 5 mM). Acute colonic inflammation induced in rats by the PAR2 agonist SLIGRL-NH₂ was inhibited by oral administration of GB88 (10 mg/kg) with markedly reduced edema, mucin depletion, PAR2 receptor internalization, and mastocytosis. Chronic TNBS-induced colitis in rats was ameliorated by GB88 (10 mg/kg/day p.o.), which reduced mortality and pathology (including colon obstruction, ulceration, wall thickness, and myeloperoxidase release) more effectively than the clinically used drug sulfasalazine (100 mg/kg/day p.o.). These disease-modifying properties for the PAR2 antagonist in both acute and chronic experimental colitis strongly support a pathogenic role for PAR2 and PAR2-activating proteases and therapeutic potential for

  3. Validation and optimization of experimental colitis induction in rats using 2, 4, 6-trinitrobenzene sulfonic acid

    PubMed Central

    Motavallian-Naeini, A.; Andalib, S.; Rabbani, M.; Mahzouni, P.; Afsharipour, M.; Minaiyan, M.

    2012-01-01

    Trinitrobenzene sulfonic acid (TNBS)-induced colitis is one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes. Our aim was to validate the main contributing factors to this method and compare the effects of different reference drugs upon remission of resultant colon injuries. TNBS was dissolved in 0.25 ml of ethanol (50% v/v) and instilled (25, 50, 100 and 150 mg/kg) intracolonically to the male Wistar rats. After determination of optimum dose of TNBS in male rats and assessment of this dose in female rats, they were treated with reference drugs including dexamethasone [1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)], Asacol (mesalazine, 100 mg/kg, p.o.; 150 mg/kg, enema) and hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) which started 2 h after colitis induction and continued daily for 6 consecutive days. Thereafter, macroscopic and microscopic parameters and clinical features were assessed and compared in different groups. We found that the optimum dose of TNBS for the reproducibility of colonic damage with the least mortality rate was 50 mg/kg. Amongst studied reference drugs, hydrocortisone acetate (i.p.), dexamethasone (i.p. and p.o.) and Asacol (p.o.) significantly diminished the severity of macroscopic and microscopic injuries and could be considered effective for experimental colitis studies in rats . Our findings suggest that optimization of TNBS dose is essential for induction of colitis under the laboratory conditions; and gender exerts no impact upon macroscopic and histological characteristics of TNBS-induced colitis in rats. Furthermore, the enema forms of hydrocortisone and Asacol are not appropriate reference drugs. PMID:23181094

  4. Validation and optimization of experimental colitis induction in rats using 2, 4, 6-trinitrobenzene sulfonic acid.

    PubMed

    Motavallian-Naeini, A; Andalib, S; Rabbani, M; Mahzouni, P; Afsharipour, M; Minaiyan, M

    2012-07-01

    Trinitrobenzene sulfonic acid (TNBS)-induced colitis is one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes. Our aim was to validate the main contributing factors to this method and compare the effects of different reference drugs upon remission of resultant colon injuries. TNBS was dissolved in 0.25 ml of ethanol (50% v/v) and instilled (25, 50, 100 and 150 mg/kg) intracolonically to the male Wistar rats. After determination of optimum dose of TNBS in male rats and assessment of this dose in female rats, they were treated with reference drugs including dexamethasone [1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)], Asacol (mesalazine, 100 mg/kg, p.o.; 150 mg/kg, enema) and hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) which started 2 h after colitis induction and continued daily for 6 consecutive days. Thereafter, macroscopic and microscopic parameters and clinical features were assessed and compared in different groups. We found that the optimum dose of TNBS for the reproducibility of colonic damage with the least mortality rate was 50 mg/kg. Amongst studied reference drugs, hydrocortisone acetate (i.p.), dexamethasone (i.p. and p.o.) and Asacol (p.o.) significantly diminished the severity of macroscopic and microscopic injuries and could be considered effective for experimental colitis studies in rats . Our findings suggest that optimization of TNBS dose is essential for induction of colitis under the laboratory conditions; and gender exerts no impact upon macroscopic and histological characteristics of TNBS-induced colitis in rats. Furthermore, the enema forms of hydrocortisone and Asacol are not appropriate reference drugs. PMID:23181094

  5. Healing Effect of Pistacia Atlantica Fruit Oil Extract in Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Tanideh, Nader; Masoumi, Samira; Hosseinzadeh, Massood; Safarpour, Ali Reza; Erjaee, Hoda; Koohi-Hosseinabadi, Omid; Rahimikazerooni, Salar

    2014-01-01

    Background: Considering the anti-oxidant properties of Pistacia atlantica and lack of data regarding its efficacy in the treatment of ulcerative colitis, this study aims at investigating the effect of the Pistacia atlantica fruit extract in treating experimentally induced colitis in a rat model. Methods: Seventy male Sprague-Dawley rats (weighing 220±20 g) were used. All rats fasted 24 hours before the experimental procedure. The rats were randomly divided into 7 groups, each containing 10 induced colitis with 2ml acetic acid (3%). Group 1 (Asacol), group 2 (base gel) and group 7 (without treatment) were assigned as control groups. Group 3 (300 mg/ml) and group 4 (600 mg/ml) received Pistacia atlantica fruit orally. Group 5 (10% gel) and group 6 (20% gel) received Pistacia atlantica in the form of gel as enema. Macroscopic, histopathological examination and MDA measurement were carried out. Results: All groups revealed significant macroscopic healing in comparison with group 7 (P<0.001). Regarding microscopic findings in the treatment groups compared with group 7, the latter group differed significantly with groups 1, 2, 4 and 6 (P<0.001). There was a significant statistical difference in MDA scores of the seven treatment groups (F(5,54)=76.61, P<0.001). Post-hoc comparisons indicated that the mean±SD score of Asacol treated group (1.57±0.045) was not significantly different from groups 4 (1.62±0.024) and 6 (1.58±0.028). Conclusion: Our study showed that a high dose of Pistacia atlantica fruit oil extract, administered orally and rectally can improve colitis physiologically and pathologically in a rat model, and may be efficient for ulcerative colitis. PMID:25429174

  6. Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

    PubMed Central

    Santana, Alfredo; Medina, Carlos; Paz-Cabrera, Maria Cristina; Díaz-Gonzalez, Federico; Farré, Esther; Salas, Antonio; Radomski, Marek W; Quintero, Enrique

    2006-01-01

    AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice. METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation. PMID:17072979

  7. Effectiveness of a hydroxynaphthoquinone fraction from Arnebia euchroma in rats with experimental colitis

    PubMed Central

    Fan, Hua-Ying; Zhang, Zi-Liang; Liu, Ke; Yang, Ming-Yan; Lv, Wei-Hong; Che, Xin; Xu, Hui; Song, Wei-Wei

    2013-01-01

    AIM: To evaluate the potential effectiveness of hydroxynaphthoquinone mixture (HM) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: Colitis was induced by intracolonic administration of TNBS (80 mg/kg, dissolved in 50% ethanol). Rats were treated daily for 7 d with HM (2.5, 5, 10 mg/kg) and mesalazine 100 mg/kg 24 h after TNBS instillation. Disease progression was monitored daily by observation of clinical signs and body weight change. At the end of the experiment, macroscopic and histopathologic lesions of rats were scored, and myeloperoxidase (MPO) activity was determined. We also determined inflammatory cytokine tumor necrosis factor (TNF)-α level by ELISA, Western blotting and immunochemistry to explore the potential mechanisms of HM. RESULTS: After intracolonic instillation of TNBS, animals developed colitis associated with soft stool, diarrhea and marked colonic destruction. Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner. It abrogated body weight loss, diarrhea and inflammation, decreased macroscopic damage score, and improved histological signs, with a significant reduction of inflammatory infiltration, ulcer size and the severity of goblet cell depletion (all P < 0.05 vs TNBS alone group). HM could reduce MPO activity. In addition, it also decreased serum TNF-α level and down-regulated TNF-α expression in colonic tissue. This reduction was statistically significant when the dose of HM was 10 mg/kg (P < 0.05 vs TNBS alone group), and the effect was comparable to that of mesalazine and showed no apparent adverse effect. The underlying mechanism may be associated with TNF-α inhibition. CONCLUSION: These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application. PMID:24409058

  8. Can red cell distribution width be a marker of disease activity in ulcerative colitis?

    PubMed Central

    Ipek, Serkan; Cekic, Cem; Alper, Emrah; Coban, Eyup; Eliacik, Eylem; Arabul, Mahmut; Aslan, Fatih; Vatansever, Sezgin; Yalcin, Hulya; Unsal, Belkis

    2015-01-01

    Aim: The current study aimed to investigate the association between disease activity and red cell distribution width (RDW) levels in ulcerative colitis and to determine whether RDW can be used as a marker of disease activity in non-anemic ulcerative colitis. Methods: The RDW levels of 310 ulcerative colitis patients who underwent colonoscopy were analyzed retrospectively. The patients were divided into two groups (active disease and remission) according to the endoscopic activity index. In addition, the accuracy of RDW in determining disease activity in non-anemic patients was assessed. The efficacy of RDW in determining disease activity was compared to that of white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate. Results: Two hundred and six (66.5%) patients had active disease, and 104 (33.5%) were in remission. The mean RDW levels in patients with active ulcerative colitis and in those in remission were 16.8±2.9 and 15.5±1.4, respectively (P<0.001). Ninety-six (46.6%) patients in the active disease group and 89 (85.6%) in the remission group were non-anemic, and their respective RDW levels were 15.4±1.2 and 15.3±1.1 (P=0.267). The sensitivity and specificity of RDW in determining inflammation were 41% and 91%, respectively (AUC 0.65, P<0.001). Conclusions: This study demonstrated that RDW can be used as a marker for disease activity in ulcerative colitis, but it did not have the same efficacy in the non-anemic group. PMID:26550336

  9. The glucocorticoid budesonide has protective and deleterious effects in experimental colitis in mice.

    PubMed

    Ocón, Borja; Aranda, Carlos J; Gámez-Belmonte, Reyes; Suárez, María Dolores; Zarzuelo, Antonio; Martínez-Augustin, Olga; Sánchez de Medina, Fermín

    2016-09-15

    Glucocorticoids are widely used for the management of inflammatory bowel disease, albeit with known limitations for long-term use and relevant adverse effects. In turn, they have harmful effects in experimental colitis. We aimed to explore the mechanism and possible implications of this phenomenon. Regular and microbiota depleted C57BL/6 mice were exposed to dextran sulfate sodium (DSS) to induce colitis and treated with budesonide. Colonic inflammation and animal status were compared. In vitro epithelial models of wound healing were used to confirm the effects of glucocorticoids. Budesonide was also tested in lymphocyte transfer colitis. Budesonide (1-60μg/day) exerted substantial colonic antiinflammatory effects in DSS colitis. At the same time, it aggravated body weight loss, increased rectal bleeding, and induced general deterioration of animal status, bacterial translocation and endotoxemia. As a result, there was an associated increase in parameters of sepsis, such as plasma NOx, IL-1β, IL-6, lung myeloperoxidase and iNOS, as well as significant hypothermia. Budesonide also enhanced DSS induced colonic damage in microbiota depleted mice. These effects were correlated with antiproliferative effects at the epithelial level, which are expected to impair wound healing. In contrast, budesonide had significant but greatly diminished deleterious effects in noncolitic mice or in mice with lymphocyte transfer colitis. We conclude that budesonide weakens mucosal barrier function by interfering with epithelial dynamics and dampening the immune response in the context of significant mucosal injury, causing sepsis. This may be a contributing factor, at least in part, limiting clinical usefulness of corticoids in inflammatory bowel disease. PMID:27431777

  10. 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.

  11. 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

  12. 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. PMID:27125760

  13. Mechanism underlying the reversal of contractility dysfunction in experimental colitis by cyclooxygenase-2 inhibition.

    PubMed

    Khan, I; Oriowo, M A

    2006-03-01

    Inflammatory bowel diseases are associated with reduced colonic contractility and induction of cyclooxygenase-2. In this study a possible role of cyclooxygenase-2 in and the underlying mechanism of the reduced contractility were investigated in experimental colitis. The effects of meloxicam, a cyclooxygenase-2 selective inhibitor were examined on colonic contractility and MAP kinase p38 and ERK(1/2) expression. Colitis was induced in Sprague-Dawley male rats by intra-colonic instillation of trinitrobenzenesulphonic acid (TNBS; 40 mg/rat in 50 ethanol). The animals were divided into three groups. Group 1 (n=9) received meloxicam (3 mg/kg-day) gavage 1 h before and 1 day (Group 2) after induction of colitis. Group 3 (n=9) received phosphate buffered saline (PBS) in a similar manner and served as colitic control. The non colitic control animals received meloxicam in a similar manner. The animals were sacrificed after 5 days of treatment, colon was cleaned with PBS and colonic smooth muscle was obtained which was used in this study. Meloxicam treatment given 1 h before or 1 day after administration of colitis restored the reduced colonic contractility without affecting the sensitivity to carbachol. The levels of colonic smooth muscle IL-1beta mRNA, PGE(2), ERK(1/2), p38, malondialdehyde, myeloperoxidase activity and colonic mass were increased, whereas the body weight was decreased due to TNBS. The changes except colonic muscle mass and p38 expression were reversed by meloxicam treatment. These findings indicate that restoration of reduced colonic contractility by meloxicam is mediated by ERK(1/2), and that ERK(1/2) may serve as an important anti inflammatory target for treatment of colitis. PMID:16835710

  14. Effects of Antioxidant Therapy on Leukocyte Myeloperoxidase and Cu/Zn-Superoxide Dismutase and Plasma Malondialdehyde Levels in Experimental Colitis

    PubMed Central

    Belge Kurutas, Ergul; Cetinkaya, Ali; Bulbuloglu, Ertan; Kantarceken, Bulent

    2005-01-01

    The aim of the present study was to evaluate the effects of N-acetylcysteine (NAC) and L-carnitine (LCAR) supplementations on polymorphonuclear leukocytes myeloperoxidase (MPO) and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and plasma malondialdehyde (MDA) in acetic acid (AA)-induced ulcerative colitis model. The mean polymorphonuclear leukocyte MPO and Cu/Zn-SOD activity was significantly higher in the colitis group than in the control group. Both NAC and LCAR pretreatment markedly decreased MPO and Cu/Zn-SOD activity compared to colitis group. AA administration significantly increased the levels of plasma MDA in comparison with controls. However, NAC and LCAR administration to the AA-treated rats significantly reduced the MDA levels compared to colitis group. In conclusion NAC and LCAR could be beneficial agents in restoring the circulating proinflammatory mediators. PMID:16489261

  15. Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis.

    PubMed

    Yang, Jiayin; Xu, Lili

    2016-01-01

    BACKGROUND IL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis. MATERIAL AND METHODS Acute and chronic mouse colitis models were established by administering mice DSS in drinking water. IL-23R, IL-23, IL-I7, and IFN-γ expression level, as well as regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORgt, and T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORγt+ cells in a Foxp3+ cell population in colon mucosa during acute and chronic colitis was evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the colon mucosa from acute colitis mice and chronic colitis mice was monitored by Western blot analysis. RESULTS We detected elevated IL-23R, IL-23, and IFN-γ expression in colon mucosa during acute and chronic colitis and found increased IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was greatly enhanced, indicating the activation of IL-23R function in colitis mice. The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable to control mice, but there was a 2-fold increase of Foxp3+ RORγt+ cells among the Foxp3+ cell population in acute and chronic colitis mice compared to control mice. CONCLUSIONS These findings indicate that the induction of Foxp3+ RORgt+ T cells could be enhanced during inflammation in the intestine where IL-23R expression is greatly induced. Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of

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

    PubMed Central

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

    2015-01-01

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

  17. Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

    PubMed Central

    Ettreiki, Chourouk; Gadonna-Widehem, Pascale; Mangin, Irène; Coëffier, Moïse; Delayre-Orthez, Carine; Anton, Pauline M

    2012-01-01

    AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated using quantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis

  18. 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

  19. Induction of Indoleamine 2,3 Dioxygenase-1 by Immunostimulatory-DNA Limits Severity of Experimental Colitis

    PubMed Central

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

    2010-01-01

    The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human IBD and in experimental models of colitis there is an increased expression of the enzyme indoleamine 2,3 dioxygenase (IDO). IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine TNBS 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-DNA (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-ODN. Signaling required for intestinal IDO-1 induction involves interferon dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the TNBS and DSS models of colitis we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histologic 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-ODN 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. PMID:20181893

  20. 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. PMID:25089934

  1. Leukocytoclastic vasculitis in an adolescent with ulcerative colitis: Report of a case and review of the literature

    PubMed Central

    Butts, G Tyler; Bishop, Phyllis R; Wyatt, Julie P

    2014-01-01

    An adolescent female with long-standing, difficult-to-control ulcerative colitis developed leukocytoclastic vasculitis, a rare cutaneous extra-intestinal manifestation of the inflammatory bowel disease. The authors provide a literature review on leukocytoclastic vasculitis complicating ulcerative colitis. Furthermore, the clinical features of leukocytoclastic vasculitis are compared and contrasted with the more common cutaneous extra-intestinal manifestations of inflammatory bowel disease, erythema nodosum, and pyoderma gangrenosum.

  2. Alterations to enteric neural signaling underlie secretory abnormalities of the ileum in experimental colitis in the guinea pig.

    PubMed

    Hons, Ian M; Burda, Joshua E; Grider, John R; Mawe, Gary M; Sharkey, Keith A

    2009-04-01

    Inflammatory bowel diseases (IBD) can involve widespread gastrointestinal dysfunction, even in cases in which inflammation is localized to a single site. The underlying pathophysiology of dysfunction in noninflamed regions is unclear. We examined whether colitis is associated with altered electrogenic ion transport in the ileal mucosa and/or changes in the properties of ileal submucosal neurons. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS), and the uninflamed ileum from animals was examined 3, 7, and 28 days later. Electrogenic ion transport was assessed in Ussing chambers. Intracellular microelectrode recordings were used to examine the neurophysiology of the submucosal plexus of the ileum in animals with colitis. Noncholinergic secretion was reduced by 33% in the ileum from animals 7 days after the induction of colitis. The epithelial response to vasoactive intestinal peptide (VIP) was unaltered in animals with colitis, but the response to carbachol was enhanced. Slow excitatory synaptic transmission was dramatically reduced in VIP-expressing, noncholinergic secretomotor neurons. This change was detected as early as 3 days following TNBS treatment. No changes to fast synaptic transmission or the number of VIP neurons were observed. In addition, cholinergic secretomotor neurons fired more action potentials during a given stimulus, and intrinsic primary afferent neurons had broader action potentials in animals with colitis. These findings implicate changes to enteric neural circuits as contributing factors in inflammation-induced secretory dysfunction at sites proximal to a localized inflammatory insult. PMID:19221017

  3. 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

  4. 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

  5. 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

  6. Curcumin for maintenance of remission in ulcerative colitis

    PubMed Central

    Garg, Sushil K; Ahuja, Vineet; Sankar, Mari Jeeva; Kumar, Atul; Moss, Alan C

    2014-01-01

    Background Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission. There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated. Objectives The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC. Search methods A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies. Selection criteria Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed. Data collection and analysis Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI. Main results Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low

  7. Surgical Treatment of Crohn Colitis Involving More Than 2 Colonic Segments

    PubMed Central

    Lee, Jong Lyul; Yu, Chang Sik; Lim, Seok-Byung; Park, In Ja; Yoon, Yong Sik; Kim, Chan Wook; Yang, Suk-Kyun; Kim, Jin Cheon

    2016-01-01

    Abstract The incidence of primary Crohn colitis is uncommon and surgical treatment has remained controversial, although most patients with Crohn colitis eventually require surgical intervention. This study aims to compare the operative outcomes of patients who underwent segmental versus either total colectomy or total proctocolectomy for Crohn colitis and to assess potential risk factors associated with clinical and surgical recurrence-free survivals. This is a retrospective study of 116 patients who underwent primary surgery for Crohn colitis between August 1997 and July 2011. Patients were classified based on the type of surgery: segmental colectomy (SC group; n = 71) or either total colectomy or total proctocolectomy (TC group; n = 45). There were no significant differences in postoperative complications or the nutritional state between the SC and TC groups. Patients in TC group had a significantly higher clinical recurrence-free survival (CRFS). Among the 54 patients with multisegmental Crohn colitis, the TC group had a significantly increased CRFS and surgical recurrence-free survival (SRFS), compared with patients in the SC group (5-year CRFS: 82.0% ± 5.8% vs 22.2% ± 13.9%, P = 0.001; 5-year SRFS: 88.1% ± 5.0% vs 44.4% ± 16.6%, P = 0.001). By multivariate analysis of patients with multisegments involved, SC was a risk factor for SRFS and CRFS (hazard ratio [HR] = 4.637, 95% confidence interval [CI] = 1.387–15.509, P = 0.013 and HR = 32.407, 95% CI = 2.873–365.583, P = 0.005). TC patients have significantly increased CRFS and TC in patients with multisegment involvement may affect improved SRFS and CRFS. Among patients with multisegmental Crohn colitis, SC is an independent risk factor for CRFS and SRFS. PMID:27258512

  8. The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

    PubMed Central

    2011-01-01

    Background This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. Methods Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \\ groups (control, colitis, HFD and colitis + HFD). Results Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. Conclusion Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream. PMID:22073943

  9. Cytomegalovirus Colitis in a Critically Ill Patient Following Severe Legionella Pneumonia with Multiple Organ Failure.

    PubMed

    Nakashima, Kei; Aoshima, Masahiro; Suzuki, Fumi; Watanabe, Junko; Otsuka, Yoshihito

    2016-01-01

    A 68-year-old man visited an emergency department complaining of dyspnea. He was diagnosed to have Legionella pneumonia with multiple organ failure. Although his multiple organ failure improved, he suffered from persistent abdominal pain and diarrhea with continuous minor bleeding. Colonoscopy revealed a longitudinal ulcer of the rectum, below the peritoneal reflection. He was diagnosed with cytomegalovirus (CMV) colitis. Antiviral therapy with ganciclovir was initiated. He finally underwent a colostomy after a bowel stricture caused an intestinal outlet obstruction, which made oral intake impossible. Based on the present case, we believe that CMV colitis must be considered as one of the differential diagnoses when critically ill patients develop continuous diarrhea and abdominal pain. PMID:26935377

  10. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis

    PubMed Central

    Katoh, Hiroshi; Wang, Dingzhi; Daikoku, Takiko; Sun, Haiyan; Dey, Sudhansu K.; DuBois, Raymond N.

    2013-01-01

    Summary A large body of evidence indicates that chronic inflammation is one of key risk factors for cancer initiation, progression, and metastasis. However, the underlying mechanisms responsible for the contribution of inflammation and inflammatory mediators to cancer remain elusive. Here we present genetic evidence showing that loss of CXCR2 dramatically suppresses colonic chronic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid-derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis-associated cancer. CXCR2 ligands were elevated in inflamed colonic mucosa and tumors and induced MDSC chemotaxis via its receptor, CXCR2. Adoptive transfer of wild type MDSCs into Cxcr2−/− mice restored AOM/DSS-induced tumor progression. MDSCs accelerated tumor growth by inhibiting CD8+ T cell cytotoxic activity. PMID:24229710

  11. Sigmoid colon carcinoma with focal neuroendocrine differentiation associated with ulcerative colitis: A case report

    PubMed Central

    Rifu, Kazuma; Koinuma, Koji; Horie, Hisanaga; Morimoto, Mitsuaki; Kono, Yoshihiko; Tahara, Makiko; Sakuma, Yasunaru; Hosoya, Yoshinori; Kitayama, Joji; Lefor, Alan Kawarai; Sata, Naohiro; Suzuki, Tsukasa; Fukushima, Noriyoshi

    2016-01-01

    Introduction Neuroendocrine tumors of the colon and rectum are relatively rare compared to sporadic colorectal carcinoma. There are few reports of neuroendocrine tumors of the colon and rectum in patients with ulcerative colitis. Presentation of case A patient with sigmoid colon carcinoma with focal neuroendocrine features is presented. A 32-year-old man, who had been followed for ulcerative colitis for 14 years, was found to have carcinoma of the sigmoid colon on routine annual colonoscopy, and he underwent laparoscopic total colectomy. Pathologic examination showed sigmoid colon adenocarcinoma with focal neuroendocrine features. Discussion Most colorectal carcinomas associated with inflammatory bowel disease are histologically similar to the sporadic type, and tumors with neuroendocrine features are very unusual. Conclusion Very rare case of sigmoid colon carcinoma with neuroendocrine features arising in a patient with UC was described. PMID:27136202

  12. 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

  13. Acute ischemic colitis during scuba diving: Report of a unique case

    PubMed Central

    Goumas, Konstantinos; Poulou, Androniki; Tyrmpas, Ioannis; Dandakis, Dimitrios; Bartzokis, Stavros; Tsamouri, Magdalini; Barbati, Kalipso; Soutos, Dimitrios

    2008-01-01

    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. PMID:18506937

  14. 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

  15. Passage of a Sigmoid Colon Cast in a Patient With Ischemic Colitis

    PubMed Central

    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. PMID:25216411

  16. 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. PMID:25149009

  17. 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

  18. [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

  19. 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

  20. A case report of severe ulcerative colitis with mediastinal and subcutaneous emphysema.

    PubMed

    Terasaki, Kei; Okuyama, Yusuke; Ueda, Tomohiro; Matsuyama, Kiichi; Urata, Yoji; Yoshida, Norimasa

    2016-03-01

    A 17-year-old boy developed prominent mediastinal and subcutaneous emphysema while receiving treatment with 5-aminosalicylic acid (5-ASA) and oral corticosteroids for severe ulcerative colitis. We ruled out infection and initiated oral administration of tacrolimus, after which both the underlying disease and mediastinal and subcutaneous emphysema improved. However, he continued to experience repeated bouts of ulcerative colitis, so we ultimately opted for surgical intervention. Although mediastinal and subcutaneous emphysema is rare, it is one of the known extra-intestinal complications and can be particularly concerning. In this patient, mediastinal and subcutaneous emphysema might have been caused by the vulnerability of pulmonary alveolar walls to steroid medication and the increase of pulmonary alveolar pressure with abdominal pain and breath holding. Here, we report a case of inflammatory bowel disease with mediastinal and subcutaneous emphysema, along with a review of the literature. PMID:26947047

  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. 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

  3. [EHEC-associated colon stenosis after ulcerous-chronic haemorrhagic colitis and consecutive resulting ileus].

    PubMed

    Lipp, M J; Schirmer, J; Feyerabend, B; Stavrou, G A; Cordruwisch, W; Faiss, S; Oldhafer, K J

    2012-05-01

    We report on the case of a segmentally emphasised, ulcerous chronic haemorrhagic colitis with the development of granulation tissue und scarred fibrosis with consecutive resulting stenosis of the colon. A 49-year-old male patient was infected with enterohaemorrhagic Escherichia coli bacteria during the EHEC-epidemic in northern Germany in early summer 2011. In the course of the infection the patient suffered from haemolytic uraemic syndrome (HUS) with acute renal failure and neurological symptoms. Haemodialysis and plasmapheresis had become mandatory. A simultaneous ileus was estimated to be of paralytic origin. One month after treatment of the acute phase of the infection a CT scan of the abdomen was performed and discovered a symptomatic stenosis of the proximal colon transversum. This obstruction needed to be treated by performing a right hemicolectomy with an ileo-transverso anastomosis. After surgery the patient recovered continuously. The histopathological examination verified an ulcerous-chronic haemorrhagic colitis on the background of an EHEC infection. PMID:22581700

  4. 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

  5. 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. PMID:23453305

  6. 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

  7. The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment

    PubMed Central

    Schicho, Rudolf; Bashashati, Mohammad; Bawa, Misha; McHugh, Douglas; Saur, Dieter; Hu, Huang-Ming; Zimmer, Andreas; Lutz, Beat; Mackie, Ken; Bradshaw, Heather B.; McCafferty, Donna-Marie; Sharkey, Keith A.; Storr, Martin

    2010-01-01

    Background Cannabinoids are known to reduce intestinal inflammation. Atypical cannabinoids produce pharmacological effects via unidentified targets. We were interested whether the atypical cannabinoid O-1602, reportedly an agonist of the putative cannabinoid receptor GPR55, reduces disease severity of dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6N and CD1 mice. Methods DSS (2.5% and 4%) was supplied in drinking water for one week while TNBS (4 mg) was applied as a single intrarectal bolus. Results Both treatments caused severe colitis. Injection of O-1602 (5 mg/kg i.p.) significantly reduced macroscopic and histological colitis scores, and myeloperoxidase activity. The protective effect was still present in cannabinoid receptor 1 (CB1) and 2 (CB2) double knockout mice and mice lacking the GPR55 gene. To investigate a potential mechanism underlying the protection by O-1602 we performed neutrophil chemotactic assays. O-1602 concentration-dependently inhibited migration of murine neutrophils to keratinocyte-derived chemokine (KC), N-formyl-methionyl-leucyl-phenylalanine (fMLP) and the N-formyl-peptide receptor ligand WKYMVm. The inhibitory effect of O-1602 was preserved in neutrophils from CB1/CB2 double knockout and GPR55 knockout mice. No differences were seen in locomotor activity between O-1602-treated and control mice indicating lack of central sedation by this compound. Conclusions Our data demonstrate that O-1602 is protective against experimentally induced colitis and inhibits neutrophil recruitment independently of CB1, CB2 and GPR55 receptors. Thus, atypical cannabinoids represent a novel class of therapeutics that may be useful for the treatment of inflammatory bowel diseases. PMID:21744421

  8. 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

  9. Curcumin-piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy.

    PubMed

    Li, Qiuping; Zhai, Wenwen; Jiang, Qiaoli; Huang, Ruixue; Liu, Lehuan; Dai, Jundong; Gong, Weihong; Du, Shouying; Wu, Qing

    2015-07-25

    Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment. PMID:25957703

  10. Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis

    PubMed Central

    Rapalli, Alberto; Bertoni, Simona; Arcaro, Valentina; Saccani, Francesca; Grandi, Andrea; Vivo, Valentina; Cantoni, Anna M.; Barocelli, Elisabetta

    2016-01-01

    Background and Aims: Changes in gut serotonin (5-HT) content have been described in Inflammatory Bowel Disease (IBD) and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous 5-HT through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of IBD. Materials and Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT3 (Ondansetron), 5-HT4 (GR125487), 5-HT7 (SB269970) receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylamino)tetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4, and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it. Conclusion: The prevailing deleterious contribution given by endogenous 5-HT to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders. PMID:27047383

  11. 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. PMID:26771865

  12. 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. PMID:26878790

  13. Targeting Mitochondria-Derived Reactive Oxygen Species to Reduce Epithelial Barrier Dysfunction and Colitis

    PubMed Central

    Wang, Arthur; Keita, Åsa V.; Phan, Van; McKay, Catherine M.; Schoultz, Ida; Lee, Joshua; Murphy, Michael P.; Fernando, Maria; Ronaghan, Natalie; Balce, Dale; Yates, Robin; Dicay, Michael; Beck, Paul L.; MacNaughton, Wallace K.; Söderholm, Johan D.; McKay, Derek M.

    2015-01-01

    Epithelial permeability is often increased in inflammatory bowel diseases. We hypothesized that perturbed mitochondrial function would cause barrier dysfunction and hence epithelial mitochondria could be targeted to treat intestinal inflammation. Mitochondrial dysfunction was induced in human colon-derived epithelial cell lines or colonic biopsy specimens using dinitrophenol, and barrier function was assessed by transepithelial flux of Escherichia coli with or without mitochondria-targeted antioxidant (MTA) cotreatment. The impact of mitochondria-targeted antioxidants on gut permeability and dextran sodium sulfate (DSS)–induced colitis in mice was tested. Mitochondrial superoxide evoked by dinitrophenol elicited significant internalization and translocation of E. coli across epithelia and control colonic biopsy specimens, which was more striking in Crohn’s disease biopsy specimens; the mitochondria-targeted antioxidant, MitoTEMPO, inhibited these barrier defects. Increased gut permeability and reduced epithelial mitochondrial voltage-dependent anion channel expression were observed 3 days after DSS. These changes and the severity of DSS-colitis were reduced by MitoTEMPO treatment. In vitro DSS-stimulated IL-8 production by epithelia was reduced by MitoTEMPO. Metabolic stress evokes significant penetration of commensal bacteria across the epithelium, which is mediated by mitochondria-derived superoxide acting as a signaling, not a cytotoxic, molecule. MitoTEMPO inhibited this barrier dysfunction and suppressed colitis in DSS-colitis, likely via enhancing barrier function and inhibiting proinflammatory cytokine production. These novel findings support consideration of MTAs in the maintenance of epithelial barrier function and the management of inflammatory bowel diseases. PMID:25034594

  14. Characterization of Chromosomal Instability in Murine Colitis-Associated Colorectal Cancer

    PubMed Central

    Gerling, Marco; Glauben, Rainer; Habermann, Jens K.; Kühl, Anja A.; Loddenkemper, Christoph; Lehr, Hans-Anton; Zeitz, Martin; Siegmund, Britta

    2011-01-01

    Background Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carcinogenesis in the gut is particularly challenging. Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas. The aim of this study was to analyze mouse models of CAC with regard to CIN. Additionally, protein expression of p53, beta-catenin and Ki67 was measured to further characterize murine tumor development in comparison to UC-associated carcinogenesis in men. Methods The AOM/DSS model (n = 23) and IL-10−/− mice (n = 8) were applied to monitor malignancy development via endoscopy and to analyze premalignant and malignant stages of CACs. CIN was assessed using DNA-image cytometry. Protein expression of p53, beta-catenin and Ki67 was evaluated by immunohistochemistry. The degree of inflammation was analyzed by histology and paralleled to local interferon-γ release. Results CIN was detected in 81.25% of all murine CACs induced by AOM/DSS, while all carcinomas that arose in IL-10−/− mice were chromosomally stable. Beta-catenin expression was strongly membranous in IL-10−/− mice, while 87.50% of AOM/DSS-induced tumors showed cytoplasmatic and/or nuclear translocation of beta-catenin. p53 expression was high in both models and Ki67 staining revealed higher proliferation of IL-10−/−-induced CACs. Conclusions AOM/DSS-colitis, but not IL-10−/− mice, could provide a powerful murine model to mechanistically investigate CIN in colitis-associated carcinogenesis. PMID:21799775

  15. 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

  16. Reduced susceptibility of mice overexpressing transforming growth factor α to dextran sodium sulphate induced colitis

    PubMed Central

    Egger, B; Carey, H; Procaccino, F; Chai, N; Sandgren, E; Lakshmanan, J; Buslon, V; French, S; Buchler, M; Eysselein, V

    1998-01-01

    Background—Transforming growth factor α (TGF-α) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis. 
Aim—To substantiate the findings that TGF-α is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF-α to DSS induced colitis. 
Methods—TGF-α overexpression was induced in transgenic mice by ZnSO4 administration in drinking water (TG+). Three groups were used as controls: one transgenic group without ZnSO4 administration (TG−), and two non-transgenic littermate groups receiving ZnSO4 (Non-TG+) or only water (Non-TG−). Acute colitis was induced in all groups by administration of DSS (5%, w/v) in drinking water for six days ad libitum. 
Results—About 35-39% of the entire colonic mucosa was destroyed in Non-TG−, Non-TG+, and TG− animals compared with 9% in TG+ mice. The crypt damage score was 18.7 (0.9), 18.2 (1.0), 18.9(0.8), and 6.8 (1.5) (means (SEM)) in Non-TG−, Non-TG+, TG−, and TG+ mice respectively. Mucin and bromodeoxyuridine staining were markedly enhanced in colons of TG+ mice compared with controls, indicating increased mucosal protection and regeneration. 
Conclusions—The significantly reduced susceptibility of mice overexpressing TGF-α to DSS further substantiates that endogenous TGF-α is a pivotal mediator of protection and/or healing mechanisms in the colon. 

 Keywords: transforming growth factor α; epidermal growth factor; dextran sodium sulphate; colitis; inflammatory bowel disease; transgenic mice PMID:9771407

  17. Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

    PubMed Central

    Lied, Gülen Arslan; Milde, Anne Marita; Nylund, Kim; Mujic, Maja; Grimstad, Tore; Hausken, Trygve; Gilja, Odd Helge

    2012-01-01

    Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS) in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS). Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha) and fecal samples (HemoFEC occult blood) were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS-induced colitis was able to be visualized by transabdominal sonography. Moreover, ultrasound findings, occult blood sampling, and histological findings supported each other, indicating that ultrasonography can be used to assess inflammation in a rat experimental model. PMID:23055765

  18. 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

  19. 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

  20. [Ischemic colitis: a report of 2 cases of ischemic gangrene of the colon].

    PubMed

    Mandarano, R; Ciccone, A; Venturini, N

    1996-03-01

    Two personal cases of ischaemic gangrene of the colon required emergency surgery. The two cases provide the basis for a discussion of the aetiopathogenetic, anatomo-pathological and clinical aspects of this pathology. Stress is laid on the fact that ischaemic colitis in its various anatomo-pathological signs is not easy to diagnose and needs early treatment of conservative or emergency surgery type depending on its anatomo-pathological expression. PMID:8684654

  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. PMID:27601997

  2. Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.

    PubMed

    Zou, Ying; Dai, Shi-Xue; Chi, Hong-Gang; Li, Tao; He, Zhi-Wei; Wang, Jian; Ye, Cai-Guo; Huang, Guo-Liang; Zhao, Bing; Li, Wen-Yang; Wan, Zheng; Feng, Jin-Shan; Zheng, Xue-Bao

    2015-10-01

    Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor α, IL-1β, and Th1-related cytokines IL-12 and IFN-γ. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor γt. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-β and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis. PMID:25269538

  3. Anaphylactoid Reaction from IV Contrast Dye Causing Ischemic Colitis with Portal Venous Gas.

    PubMed

    Adesina, Adeleke; Colombo, Adam; Jeanmonod, Rebecca

    2015-01-01

    Portal venous gas is a radiographic finding with numerous causes. The most common etiologies include bowel ischemia or other intra-abdominal catastrophes. The finding of portal venous gas carries a high mortality rate. We report the first case of portal venous gas associated with anaphylactoid reaction to intravenous contrast dye in a middle-aged woman. This was likely secondary to anaphylactoid-induced ischemic colitis. This patient was managed conservatively and had a good outcome. PMID:25984370

  4. Correlation Between Low Bone Density and Disease Activity in Patients with Ulcerative Colitis

    PubMed Central

    Amiriani, Taghi; Besharat, Sima; Pourramezan, Zahra; Mirkarimi, Honey Sadat; Aghaei, Mehrdad; Joshaghani, Hamidreza; Roshandel, Gholamreza; Faghani, Maryam; Besharat, Mahsa

    2015-01-01

    BACKGROUND Different clinical and epidemiological studies using dual-energy X-ray absorptiometry have shown an increased prevalence of low bone mineral density in patients with inflammatory bowel diseases. The aim of this study was to assess the correlation between bone density and the disease activity in patients with ulcerative colitis. METHODS In this cross-sectional study, 52 patients with ulcerative colitis (duration of the disease less than 5 years) were invited to our research center, Golestan province, northeast of Iran, during February 2012 up to August 2012. A demographic checklist and Simple Clinical Colitis Activity Index was completed for each patients and 5 cc of blood sample was taken after obtaining the informed consent. We used colorimetry method for measuring serum calcium, UV method for serum phosphorus and ELISA for serum vitamin D. Dual-energy X-ray absorptiometry was done to evaluate the bone density. Data analysis was done using SPSS software version 16. Normality of data was assessed using Kolmogorov– Smirnov test. T and ANOVA tests were used if data had normal distribution. Mann-Whitney U or Kruskal-Wallis tests were used for the remaining data. Correlation between qualitative variables was evaluated by Chi-square test. RESULTS The mean (±SD) age and disease activity of the patients were 37.72 (±12.18) years and 4.78 (±1.98), respectively. There were no correlation between disease activity and mean age. Low bone density was seen in 30.8%, 11.5%, and 15.4% in spine, femur neck, and hip, respectively. There was no relationship between Z-score of total hip, spine, and femur neck with disease activity, age, and duration of disease (p>0.05). CONCLUSION Our results showed an acceptable rate of low bone density in patients with ulcerative colitis without any correlation with the disease activity index. PMID:25628850

  5. Correlation between low bone density and disease activity in patients with ulcerative colitis.

    PubMed

    Amiriani, Taghi; Besharat, Sima; Pourramezan, Zahra; Mirkarimi, Honey Sadat; Aghaei, Mehrdad; Joshaghani, Hamidreza; Roshandel, Gholamreza; Faghani, Maryam; Besharat, Mahsa

    2015-01-01

    BACKGROUND Different clinical and epidemiological studies using dual-energy X-ray absorptiometry have shown an increased prevalence of low bone mineral density in patients with inflammatory bowel diseases. The aim of this study was to assess the correlation between bone density and the disease activity in patients with ulcerative colitis. METHODS In this cross-sectional study, 52 patients with ulcerative colitis (duration of the disease less than 5 years) were invited to our research center, Golestan province, northeast of Iran, during February 2012 up to August 2012. A demographic checklist and Simple Clinical Colitis Activity Index was completed for each patients and 5 cc of blood sample was taken after obtaining the informed consent. We used colorimetry method for measuring serum calcium, UV method for serum phosphorus and ELISA for serum vitamin D. Dual-energy X-ray absorptiometry was done to evaluate the bone density. Data analysis was done using SPSS software version 16. Normality of data was assessed using Kolmogorov- Smirnov test. T and ANOVA tests were used if data had normal distribution. Mann-Whitney U or Kruskal-Wallis tests were used for the remaining data. Correlation between qualitative variables was evaluated by Chi-square test. RESULTS The mean (±SD) age and disease activity of the patients were 37.72 (±12.18) years and 4.78 (±1.98), respectively. There were no correlation between disease activity and mean age. Low bone density was seen in 30.8%, 11.5%, and 15.4% in spine, femur neck, and hip, respectively. There was no relationship between Z-score of total hip, spine, and femur neck with disease activity, age, and duration of disease (p>0.05). CONCLUSION Our results showed an acceptable rate of low bone density in patients with ulcerative colitis without any correlation with the disease activity index. PMID:25628850

  6. Interferon β-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study

    PubMed Central

    Nikolaus, S; Rutgeerts, P; Fedorak, R; Steinhart, A H; Wild, G E; Theuer, D; Möhrle, J; Schreiber, S

    2003-01-01

    Background and aims: Administration of interferon (IFN)-β may represent a rational approach to the treatment of ulcerative colitis through its immunomodulatory and anti-inflammatory effects. The present study was performed to evaluate the efficacy and tolerability of IFN-β-1a. Methods: Patients (n=18) with moderately active ulcerative colitis were randomised to receive IFN-β-1a or placebo. IFN-β-1a was started at a dose of 22 μg three times a week subcutaneously, and the dose was increased at two week intervals to 44 μg and then to 88 μg if no response was observed. The maximum duration of treatment was eight weeks. End points were clinical treatment response, defined as a decrease of at least 3 points from baseline in the ulcerative colitis scoring system (UCSS) symptoms score and induction of endoscopically confirmed remission. Results: Baseline characteristics and disease severity were similar in both groups. Data from 17 patients are included in this report (10 patients in the IFN-β-1a group and seven patients in the placebo group). Clinical response was achieved in five patients (50%) in the IFN-β-1a group and in one (14%) in the placebo group (P=0.14). Remission was achieved in three patients in the IFN-β-1a group and in none in the placebo group (p=0.02). Most adverse reactions associated with IFN-β-1a were influenza-like symptoms or injection site reactions, and were mild or moderate in severity. Conclusions: IFN-β-1a may represent a promising novel treatment approach in ulcerative colitis. PMID:12912859

  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 whet