Mechanism of diarrhea in microscopic colitis.

Science.gov (United States)

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

2005-09-21

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

Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis

NARCIS (Netherlands)

Cantaert, Tineke; Doorenspleet, Marieke E.; Francosalinas, Gabriela; Paramarta, Jaqueline E.; Klarenbeek, Paul L.; Tiersma, Yvonne; van der Loos, Chris M.; de Vries, Niek; Tak, Paul Peter; Baeten, Dominique L.

2012-01-01

Objective Whether and how B lymphocytes contribute to the pathogenesis of spondylarthritis (SpA), a seronegative arthritis associated with gut inflammation, remains unknown. Because innate-like CD5+ B lymphocytes with regulatory functions have been identified in colitis models, we undertook the

Neutrophilic dermatoses in a patient with collagenous colitis

Directory of Open Access Journals (Sweden)

Didac Barco

2010-01-01

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

Management of pediatric ulcerative colitis

DEFF Research Database (Denmark)

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

2012-01-01

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

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

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Ha, Christina; Kornbluth, Asher

2014-12-01

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

Neutrophilic dermatoses in a patient with collagenous colitis

OpenAIRE

Didac Barco; Maria A. Barnadas; Esther Roé; Francisco J. Sancho; Elena Ricart; Agustín Alomar

2010-01-01

We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate...

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

Science.gov (United States)

Ha, Christina

2014-01-01

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

Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

Science.gov (United States)

Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

2018-04-25

Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

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

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Hamid Tavakoli

2008-08-01

Full Text Available

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

IL-9 antibody injection suppresses the inflammation in colitis mice

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

2015-12-25

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

IL-9 antibody injection suppresses the inflammation in colitis mice

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis.

Science.gov (United States)

Tang, Haowen; Lu, Wenping; Li, Bingmin; Li, Chonghui; Xu, Yinzhe; Dong, Jiahong

2017-05-30

Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.

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

Science.gov (United States)

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

2014-06-30

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

Biomarkers and Microscopic Colitis: An Unmet Need in Clinical Practice

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Laura Francesca Pisani

2017-05-01

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

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

OpenAIRE

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

2014-01-01

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

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

Science.gov (United States)

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

2014-03-01

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

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

Science.gov (United States)

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

2017-04-01

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

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

Directory of Open Access Journals (Sweden)

J. D. van Bergeijk

1998-01-01

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

[Effect of Electroacupuncture Stimulation of "Guanyuan" (CV 4) and "Zusanli" (ST 36) on Spleen Lymphocytes Treg/Th 17 Immune Balance in Ulcerative Colitis Mice].

Science.gov (United States)

Wang, Cheng-yu-lin; Zeng, Lin-lan; Geng, Yu; Wang, Xiang; Zhang, He-jiao; Yang, Hui; Wu, Qiao- feng; Yu, Shu-guang

2016-02-01

To observe the effect of electroacupuncture (EA) intervention on spleen T-helper 17 (Th 17) and regulatory T (Treg) cell levels in mice with ulcerative colitis (UC), so as to reveal its mechanisms underlying improvement of UC. METHODS Kunming mice were randomized into control, UC model and EA groups, with 8 mice in each group. The UC model was established by giving the mice with 3% Dextran Sulfate Sodium (DSS) for 5 days. EA (15 Hz/25 Hz, 0.1-0.2 mA) was applied at "Guanyuan" (CV 4) and bilateral "Zusanli" (ST 36, used alternatively) for 10 min, once a day for 5 days. The animals' disease activity index [DAl, = (body weight index score + stool score + bleeding score)/3; 0-4 points] were calculated. The pathological changes of colon tissues were observed by light microscopy after H. E. stain, and spleen Treg (CD⁴⁺ CD²⁵⁺ Foxp³⁺ Treg) and Th 17 (CD³⁺ CD⁸⁺ IL-17⁺ Th 17) lymphocyte levels were determined by flow cytometry. Compared to the control group, the DAl score and the ratio of Th 17/CD⁸⁺ T cells were significantly increased, while the ratio of Treg/CD⁴⁺ T cells obviously decreased in the model group (P Th 17/CD⁸⁺ T cells and the decreased Treg/CD⁴⁺ T cells were reversed (P Th 17 lymphocytes.

Non-IBD and noninfectious colitis

DEFF Research Database (Denmark)

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

2008-01-01

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

B7-H4-Ig treatment of normal mice changes lymphocyte homeostasis and increases the potential of regulatory T cells

DEFF Research Database (Denmark)

Kristensen, Nanna N; Schmidt, Esben G W; Rasmussen, Susanne

2013-01-01

Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professio......Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed...... of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases...

Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution, function and eAg-specific antibody secretion

DEFF Research Database (Denmark)

Venning, Freja Albjerg; Trempenau, Mette Louise; Schmidt, Esben

2013-01-01

Studies reporting beneficial effects of B lymphocytes in autoimmune diseases have been accumulating and a regulatory role for certain B cell subsets is hence getting more and more recognition. Recently, B cells were shown to exhibit a regulatory effect in a T cell transfer model of colitis. Here, B...

Colitis of Behcet's syndrome

International Nuclear Information System (INIS)

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

1980-01-01

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

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute pulmonary embolism: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Qian; Ma, Junfen; Jiang, Zhiyun; Ming, Liang

2018-02-01

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict prognosis of acute pulmonary embolism (PE). However, the prognostic value of NLR and PLR remained inconsistent between studies. The aim of this meta-analysis was to assess the prognostic role of NLR and PLR in acute PE. We systematically searched Pubmed, Embase, Web of Science and CNKI for relative literature up to March 2017. The pooled statistics for all outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). The statistical analyses were performed using Review Manager 5.3.5 analysis software and Stata software. Totally 7 eligible studies consisting of 2323 patients were enrolled in our meta-analysis. Elevated NLR was significantly associated with overall (short-term and long-term) mortality (OR 10.13, 95% CI 6.57-15.64, Panalysis revealed that NLR and PLR are promising biomarkers in predicting prognosis in acute PE patients. We suggest NLR and PLR be used routinely in the PE prognostic assessment.

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

Science.gov (United States)

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

2012-01-01

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

Systematic review with meta-analysis

DEFF Research Database (Denmark)

Roda, G; Narula, N; Pinotti, R

2017-01-01

and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. METHODS: We performed a systematic literature search to identify studies on disease extension of ulcerative colitis...... (UC) and predictors of disease progression. RESULTS: Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11...... in patients from North America (37.8%) than from Europe (19.6%) (Pmeta-analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin...

Microscopic Colitis – A Missed Diagnosis in Diarrhea-Predominant Irritable Bowel Syndrome

Science.gov (United States)

STOICESCU, Adriana; BECHEANU, Gabriel; DUMBRAVA, Mona; GHEORGHE, Cristian; DICULESCU, Mircea

2012-01-01

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

An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

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Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

2018-04-19

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

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

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Magdy El-Salhy

2011-07-01

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

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

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Islam, M S; Murata, T; Fujisawa, M; Nagasaka, R; Ushio, H; Bari, A M; Hori, M; Ozaki, H

2008-01-01

Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-κB (NF-κB) activity in macrophages. In the present study, we investigated the effect of γ-oryzanol (γ-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of γ-ORZ, and ferulic acid (FA), a possible metabolite of γ-ORZ in vivo, on a model of colitis in mice. Experimental approach: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-κB activity in colitis tissue. Key results: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-κB p65 nuclear translocation and inhibitory protein of nuclear factor-κB-α degradation levels were significantly increased in DSS-induced colitis tissues. γ-ORZ (50 mg kg−1 day−1 p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that γ-ORZ and CAF had strong antioxidant effects comparable to those of α-tocopherol. Conclusions and implications: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-κB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates. PMID:18536734

Efficacy and safety of tumor necrosis factor-α blockers for ulcerative colitis: A systematic review and meta-analysis of published randomized controlled trials

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Yun-Na Song

2015-03-01

Full Text Available To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs of TNF-α blockers for treatment of ulcerative colitis (UC were performed in PubMed, Web of Science, Embase and cochrane clinical trial. We estimated Pooled estimates of the odds ratio (OR and relevant 95% confidence interval (CI using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Nine randomized controlled studies met the selection criteria with a total of 2518 patients. Five studies compared Infliximab with placebo. Two studies compared Infliximab to corticosteroids. Two studies compared Adalimumab to placebo. One study compared subcutaneous golimumab to placebo. Short-term response, short-term remission, long-term remission and mucosal healing were better in the TNF-α blocker group than in the control group (p < 0.05. TNF-α blockers decreased the colectomy rate and serious adverse reactions (p < 0.05. The TNF-α blockers were superior to controls in achieving short-term clinical response/remission, long-term remission and mucosal healing and decreased the colectomy rate and serious adverse reactions.

Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

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Xiaodi Yang

Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

5-Aminosalicylate intolerance causing exacerbation in pediatric ulcerative colitis.

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Shimizu, Hirotaka; Arai, Katsuhiro; Tang, Julian; Hosoi, Kenji; Funayama, Rie

2017-05-01

5-Aminosalicylate (5-ASA) is widely used as the first-line drug for ulcerative colitis (UC). 5-ASA is mostly a safe and effective drug, but it can bring about exacerbation due to 5-ASA intolerance. 5-ASA intolerance can be confusing and it can mislead physicians into considering unnecessary treatment escalation, including corticosteroid (CS), biologics, or even surgery. In spite of the clinical importance of 5-ASA intolerance, there have been few studies on its incidence, clinical features, and diagnosis. In order to evaluate the incidence, characteristic symptoms, disease course, and laboratory data of children with 5-ASA intolerance, we retrospectively reviewed the medical records of 80 children with UC. Eleven of 80 children (13.8%) with UC were diagnosed with 5-ASA intolerance. The median time between the initiation of 5-ASA and the onset of 5-ASA intolerance was 10 days (range, 4-20 days) in patients not receiving CS. Drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients, and was positive in eight. C-reactive protein (CRP) increased significantly when exacerbation of colitis symptoms occurred. The incidence of 5-ASA intolerance was relatively high. Besides the challenge test, elevation of CRP and positive DLST appeared to support the diagnosis of 5-ASA intolerance. © 2017 Japan Pediatric Society.

Stercoral colitis mimicking appendicitis

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Abdelghafour Elkoundi

2017-02-01

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

Eosinophilic colitis in infants

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Adriana Chebar Lozinsky

2014-01-01

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

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

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Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

Ulcerative colitis masked by giant urticaria.

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

2007-01-01

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

Hemidesmosome integrity protects the colon against colitis and colorectal cancer.

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

2017-10-01

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

Radiologic findings in taxane induced colitis

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

2008-01-01

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

Probiotics and prebiotics in ulcerative colitis.

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

2016-02-01

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

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

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

2015-12-14

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

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

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Jairath, Vipul; Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D'Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and

Psychometric validation of the SF-36® Health Survey in ulcerative colitis: results from a systematic literature review.

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Yarlas, Aaron; Bayliss, Martha; Cappelleri, Joseph C; Maher, Stephen; Bushmakin, Andrew G; Chen, Lea Ann; Manuchehri, Alireza; Healey, Paul

2018-02-01

To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36 ® Health Survey (SF-36) in patients with ulcerative colitis (UC). We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed. Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach's α ≥ 0.70) for all SF-36 scales and test-retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales. Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

Eosinophilic colitis in infants.

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Lozinsky, Adriana Chebar; Morais, Mauro Batista de

2014-01-01

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

Temporal comorbidity of mental disorder and ulcerative colitis.

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Cawthorpe, David; Davidson, Marta

2015-01-01

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

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

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Masashi Ohno

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

CT evaluation of infectious colitis

International Nuclear Information System (INIS)

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

2002-01-01

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

CT evaluation of infectious colitis

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

2002-08-01

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

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

Science.gov (United States)

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

2013-06-01

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

Segmental Colitis Complicating Diverticular Disease

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Guido Ma Van Rosendaal

1996-01-01

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

Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis

Science.gov (United States)

... colon. The scope inflates the large intestine with air to give the gastroenterologist a better view. The camera sends a video image of the intestinal lining to a computer screen, allowing the gastroenterologist to carefully examine the tissues ...

Long-Term Natural History and Complications of Collagenous Colitis

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Hugh J Freeman

2012-01-01

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

Metabonomics in Ulcerative Colitis: Diagnostics, Biomarker Identification, And Insight into the Pathophysiology

DEFF Research Database (Denmark)

Bjerrum, Jacob T; Nielsen, Ole H; Hao, Fuhua

2010-01-01

Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate statistical analyses have been employed on mucosal colonic biopsies, colonocytes, lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in order to explore the diagnostic possibilities, define new...... potential biomarkers, and generate a better understanding of the pathophysiology. Samples were collected from patients with active UC (n = 41), quiescent UC (n = 33), and from controls (n = 25) and analyzed by NMR spectroscopy. Data analysis was carried out by principal component analysis and orthogonal......-projection to latent structure-discriminant analysis using the SIMCA P+11 software package (Umetrics, Umea, Sweden) and Matlab environment. Significant differences between controls and active UC were discovered in the metabolic profiles of biopsies and colonocytes. In the biopsies from patients with active UC higher...

Allergic colitis: a mimic of Hirschsprung disease

International Nuclear Information System (INIS)

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

1999-01-01

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

Colitis ulcerosa

DEFF Research Database (Denmark)

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

2013-01-01

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

Probiotics and prebiotics in ulcerative colitis

NARCIS (Netherlands)

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

2016-01-01

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

Unusual complication of toxic megacolon in typhoid colitis.

Science.gov (United States)

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

2014-05-01

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

Desulfovibrio bacterial species are increased in ulcerative colitis.

LENUS (Irish Health Repository)

Rowan, Fiachra

2012-02-01

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

Necrotizing colitis associated with carcinoma of the colon

International Nuclear Information System (INIS)

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

1982-01-01

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

Toxic amebic colitis coexisting with intestinal tuberculosis.

Science.gov (United States)

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

2000-01-01

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

A case of fulminating amebic colitis associated with toxic megacolon

Energy Technology Data Exchange (ETDEWEB)

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

1985-12-15

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

A case of fulminating amebic colitis associated with toxic megacolon

International Nuclear Information System (INIS)

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

1985-01-01

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

A case of fulminating amebic colitis associated with toxic megacolon

Energy Technology Data Exchange (ETDEWEB)

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

1985-12-15

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

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

Science.gov (United States)

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

2016-09-07

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

Usefulness of colonoscopy in ischemic colitis.

Science.gov (United States)

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

2010-07-01

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

Olanzapine-induced ischemic colitis

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Esteban Sáez-González

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

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

Science.gov (United States)

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

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Derek M. Tang

2014-01-01

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

Intestinal Giardiasis Disguised as Ulcerative Colitis

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Yu Zhen

2018-01-01

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

Efficacy and safety of vedolizumab as a treatment option for moderate to severe refractory ulcerative colitis in two patients after liver transplant due to primary sclerosing cholangitis

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Raúl Vicente Olmedo-Martín

Full Text Available Vedolizumab is a humanized IgG1 monoclonal antibody that selectively blocks the lymphocyte integrin α4β7 and prevents its interaction with endothelial adhesion molecules and subsequent transmigration to the gastrointestinal tract. The drug was approved in 2014 for the induction and maintenance treatment of ulcerative colitis and moderate to severe Crohn's disease that is refractory or intolerant to conventional treatment with corticoids and immunosuppressants and/or anti-TNFα drugs. However, inflammatory bowel disease has a variable behavior following liver transplant. One third of patients with ulcerative colitis associated with primary sclerosing cholangitis are expected to deteriorate despite receiving immunosuppression to prevent rejection. There is limited experience with anti-TNFα agents in patients with inflammatory bowel disease in the setting of liver transplantation and the studies to date involve a limited number of cases. The efficacy and safety data of vedolizumab in this situation are unreliable and very preliminary. We present two cases with the aim to present the efficacy and safety of vedolizumab after one year of treatment in two patients who underwent a transplant due to primary sclerosing cholangitis. One case had de novo post-transplant ulcerative colitis refractory to two anti-TNFα drugs (golimumab and infliximab. The other patient had a colostomy due to fulminant colitis and developed severe ulcerative proctitis refractory to infliximab after reconstruction with an ileorectal anastomosis.

Ulcerative colitis: pathogenesis, diagnosis, and current treatment.

Science.gov (United States)

Griffel, L H; Das, K M

1996-01-01

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

High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials

NARCIS (Netherlands)

Romkens, T.E.H.; Kampschreur, M.T.; Drenth, J.P.H.; Oijen, M.G.H. van; de Jong, D.J.

2012-01-01

BACKGROUND: Recently, mucosal healing (MH) is regarded as an important treatment goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of this study was to systematically review the medical

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

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Grant I Chen

2002-01-01

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

The role of the B lymphocytes in endometriosis: A systematic review.

Science.gov (United States)

Riccio, L G C; Baracat, E C; Chapron, C; Batteux, F; Abrão, M S

2017-09-01

The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for "endometriosis", "B cells" and "B lymphocytes" in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells. Copyright © 2017 Elsevier B.V. All rights reserved.

CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

Directory of Open Access Journals (Sweden)

Guillaume Sarrabayrouse

2014-04-01

Full Text Available How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL-10-producing Foxp3 regulatory T cells (Treg, which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL and peripheral blood lymphocytes (PBL from healthy individuals, and those with colon cancer and irritable bowel disease (IBD, we demonstrated that CD4CD8αα (DP8α T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8α LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8α PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii identify F. prausnitzii as a major inducer of these Treg, (iii argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv provide new tools to address the systemic impact of both these Treg

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

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M. Lozano Maya

2010-08-01

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

Collagenous colitis as a possible cause of toxic megacolon.

LENUS (Irish Health Repository)

Fitzgerald, S C

2009-03-01

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

Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

DEFF Research Database (Denmark)

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

2011-01-01

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

Development of chronic colitis is dependent on the cytokine MIF.

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

2001-11-01

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

Malignant change of chronic ulcerative colitis: report of a case

International Nuclear Information System (INIS)

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

1988-01-01

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

Ethnic Distribution of Microscopic Colitis in the United States.

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

2015-11-01

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

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis.

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Wang, Fan; Peng, Pai-Lan; Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

2017-11-17

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.

Acute nonsteroidal anti-inflammatory drug-induced colitis

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Massimo Tonolini

2013-01-01

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

Acute Ischaemic Colitis- A Case Report

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M Basra

2012-03-01

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

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

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

2014-04-07

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

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

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

2016-01-01

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

Value of CT in the diagnosis of pseudomembranous colitis

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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Aleksandra Matuszyk

2016-01-01

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

Amyloid Goiter Secondary to Ulcerative Colitis

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Bunyamin Aydin

2016-01-01

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

Clinical Presentation of Ulcerative Colitis in Pakistani Adults.

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Qureshi, Mustafa; Abbas, Zaigham

2015-01-01

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

T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

International Nuclear Information System (INIS)

Han, T.; Dadey, B.

1978-01-01

Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

Atypical disease phenotypes in pediatric ulcerative colitis

DEFF Research Database (Denmark)

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

2013-01-01

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

Confocal laser endomicroscopy in ulcerative colitis

DEFF Research Database (Denmark)

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

2016-01-01

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

Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.

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Pleyer, Christopher; Wiestner, Adrian; Sun, Clare

2018-05-15

Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.

Severe ischemic colitis following olanzapine use: a Case Report

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Samuel Raimundo Fernandes

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

Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

DEFF Research Database (Denmark)

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

2015-01-01

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

Inciting and etiologic agents of colitis.

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

1984-01-01

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

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

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Iclal Ocak MD,

2017-12-01

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

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

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

2016-01-01

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

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

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Qi Ying Lean

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

[Allergic colitis in exclusively breast-fed infants].

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

2006-02-01

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

Future targets for immune therapy in colitis?

DEFF Research Database (Denmark)

Kristensen, Nanna Ny; Claesson, M H

2008-01-01

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

Review article

DEFF Research Database (Denmark)

Perner, A; Rask-Madsen, J

1999-01-01

The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular im...

Management of ulcerative colitis: a clinical update

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Fabio Vieira Teixeira

2015-10-01

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

Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

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Giuseppe Scapigliati

2018-05-01

Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

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

LENUS (Irish Health Repository)

Duffy, M

2012-02-03

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

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

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

2018-03-16

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

The economics of adalimumab for ulcerative colitis.

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Xie, Feng

2015-06-01

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

Granisetron ameliorates acetic acid-induced colitis in rats.

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

2010-04-01

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

An antibiotic-responsive mouse model of fulminant ulcerative colitis.

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Silvia S Kang

2008-03-01

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

Isolated naratriptan-associated ischemic colitis

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

2016-01-01

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

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

DEFF Research Database (Denmark)

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

2008-01-01

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

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

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

2015-10-01

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

Extraintestinal manifestations in Crohn's disease and ulcerative colitis

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Isene, Rune; Bernklev, Tomm; Høie, Ole

2015-01-01

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

Ulcerative colitis presenting as leukocytoclastic vasculitis of skin

OpenAIRE

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

2008-01-01

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

Dipeptidyl peptidase expression during experimental colitis in mice

DEFF Research Database (Denmark)

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

2010-01-01

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

Development of chronic colitis is dependent on the cytokine MIF

NARCIS (Netherlands)

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

2001-01-01

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

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

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M.F. Denisova

2017-03-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

The role of aminosalicylates in the treatment of ulcerative colitis

NARCIS (Netherlands)

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

2002-01-01

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

Ulcerative colitis presenting as leukocytoclastic vasculitis of skin.

Science.gov (United States)

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

2008-04-21

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

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

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Cianciolo George

2008-03-01

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

Macrophage expression in acute radiation colitis in rats

International Nuclear Information System (INIS)

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

2003-01-01

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

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

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Joshua M Uronis

2009-06-01

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

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

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Yong-Deok Jeon

2016-04-01

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

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

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

2016-05-27

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

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

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

2011-06-01

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

Radiation effects on lymphocytes

International Nuclear Information System (INIS)

Roser, B.

1976-01-01

This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

Reactive arthritis induced by recurrent Clostridium difficile colitis

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Allison Marr

2012-01-01

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

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

Institute of Scientific and Technical Information of China (English)

Parakkal Deepak; Radha Devi

2011-01-01

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

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

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Ruuska, Tarja; Küster, Peter; Grahnquist, Lena

2016-01-01

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

Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

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Albrecht Neesse

2007-10-01

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

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

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Yonghua Bao

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

Genetics Home Reference: ulcerative colitis

Science.gov (United States)

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

Colitis ulcerosa idiopática

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Manuel Sánchez Herrera

1944-07-01

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

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

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Minutolo Vincenzo

2010-07-01

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

Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection

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Aya Nakaya

2017-12-01

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

B cells exposed to enterobacterial components suppress development of experimental colitis

DEFF Research Database (Denmark)

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

2012-01-01

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

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

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

2016-04-05

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

Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.

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Li, Ji; Yan, Yuchu; Meng, Ziran; Liu, Shuhong; Beck, Paul L; Ghosh, Subrata; Qian, Jiaming; Gui, Xianyong

2017-10-01

An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα + cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field). IBD transformers had increased IFNγ + , T-bet + , TNF-α + , and GATA-3 + LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ + and GATA-3 + cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet + , TNF-α + , and GATA-3 + cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α + and RORc + cells were seen in LC than in CC. Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.

Initial experience with golimumab in clinical practice for ulcerative colitis

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Luisa Castro-Laria

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

Sequestering HMGB1 via DNA-Conjugated Beads Ameliorates Murine Colitis

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

2014-01-01

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

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

Science.gov (United States)

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

2011-01-01

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

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

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David C Pearson

1996-01-01

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

Short-term effects of regional irradiation on lymphocytes, T lymphocytes and eosinophils

International Nuclear Information System (INIS)

Chazarin, C.; Roche, H.; Bugat, R.; Pris, F.

1983-01-01

Twenty-three cancer patients treated only by regional irradiation were studied. Radiotherapy was delivered to the pelvis in 14 patients and to the mediastinum in 9. T lymphocytes were evaluated with the Jondal technique. Before treatment, lymphocyte counts were identical in patients and control. Decreases in total lymphocytes and T lymphocytes became significant in both groups after 40 Gy. Significant rises in eosinophil counts were found only after abdominal irradiation and seemed unrelated to variations in lymphocyte counts [fr

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

Science.gov (United States)

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

2011-12-01

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

Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum

OpenAIRE

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

2007-01-01

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

Adoptive transfer of immune enhancement of experimental ulcerative colitis.

OpenAIRE

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

1984-01-01

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

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

Science.gov (United States)

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

2012-01-01

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

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

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Torigoe, Takayuki; Nakayama, Yoshifumi; Yamaguchi, Koji

2012-09-14

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

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

Science.gov (United States)

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

2015-12-01

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

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

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Ivi Ribeiro BACK

2017-03-01

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

Tetraspanin CD9 Limits Mucosal Healing in Experimental Colitis

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María Laura Saiz

2017-12-01

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

Regulating the Balance of Th17/Treg via Electroacupuncture and Moxibustion: An Ulcerative Colitis Mice Model Based Study

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Jungang Sun

2017-01-01

Full Text Available Aim. To investigate the relationship between the effects of electroacupuncture/moxibustion and the balance of Th17/Treg in treating ulcerative colitis (UC and to preliminary compare the effects of the above two methods. Methods. DSS-induced UC mice were treated by electroacupuncture and moxibustion. Disease activity index (DAI was scored; intestinal pathological structure and ultrastructure were observed. The levels of IL-2, IL-6, IL-10, IL-17A, IL-17F, and TGF-β in plasma were measured by ELISA. The percentages of Treg and Th17 in spleen lymphocytes were analyzed by flow cytometry. Also, the expressions of TLR2, TLR4, RORγt, and FOXP3 in the distal colon were detected by immunohistochemistry or western blot. Results. Both electroacupuncture and moxibustion can relieve UC. These effects are further supported by ELISA results. In addition, the ratio of Treg and Th17 in spleen lymphocytes and the expression of TLR2 and TLR4 are significantly improved. Also, the expression of RORγt and FOXP3 in distal colon were improved. Besides, the effect of moxibustion is better than that of electroacupuncture on TLR2, TLR4, and FOXP3 expression (P<0.05. Conclusion. Both electroacupuncture and moxibustion may ameliorate UC by regulating the balance of Th17/Treg. Whether moxibustion has better efficacy than electroacupuncture needs further study.

The application of molecular topology for ulcerative colitis drug discovery.

Science.gov (United States)

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

2018-01-01

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

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

Science.gov (United States)

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

2009-08-01

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

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

Science.gov (United States)

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

2005-09-01

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

THE CLINICAL SPECTRUM OF AMOEBIC COLITIS*

African Journals Online (AJOL)

1971-02-27

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

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

Science.gov (United States)

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

2015-01-01

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

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

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Aleksandra Matuszyk

2015-01-01

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

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

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Vijaya R. Bhatt

2014-02-01

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

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

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

2012-07-01

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

Synchronous cytomegalovirus infection in a newly diagnosed ulcerative colitis patient

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Jin Yu Chieng

2017-12-01

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

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastasis: A Systematic Review and Meta-Analysis.

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Tang, Haowen; Li, Bingmin; Zhang, Aiqun; Lu, Wenping; Xiang, Canhong; Dong, Jiahong

2016-01-01

Inflammation is deemed to play critical roles in tumor progression and metastasis, and an increased neutrophil-lymphocyte ratio (NLR) has been reported to correlate with poor survivals in various malignancies. However, association between NLR elevation and survival outcome in patients with colorectal liver metastasis (CRLM) remains controversial. The aim of this study was to investigate the prognostic significance of elevated NLR in CRLM. The meta-analysis was conducted in adherence to the MOOSE guidelines. PubMed, Embase, Cochrane Library, Web of Science and the Chinese SinoMed were systematically searched to identify eligible studies from the initiation of the databases to May, 2016. Overall survival (OS) and recurrence free survival (RFS) were pooled by using hazard ratio (HR) with corresponding 95% confidence interval (CI). Correlation between NLR values and clinicopathological features was synthesized by using odds ratio (OR) with corresponding 95% CI. A total of 1685 patients from 8 studies (9 cohorts) were analyzed, consisting 347 (20.59%) in high pretreatment NLR value group and 1338 (79.41%) in low pretreatment NLR value one. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR 2.17, 95% CI 1.82-2.58) and RFS (HR 1.96, 95% CI 1.64-2.35) in patients with CRLM. The result of this systematic review and meta-analysis indicated that an elevated pretreatment NLR was closely correlated with poor long-term survival (OS and RFS) in CRLM patients. NLR can be routinely monitored and serve as a useful and cost-effective marker with strong prognostic significance in patients with CRLM.

Pyoderma gangrenosum in association with microscopic colitis, idiopathic hypereosinophilic syndrome, selective IgE deficiency and diabetes mellitus.

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Riyaz, N; Sasidharanpillai, S; Rahima, S; Bindu, V; Shaan, M; Raghavan, N T; Mohan, L; Janardhanan, A K

2015-08-01

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. We report a 27-year-old male patient with diabetes, who presented with a nonhealing ulcer on the left leg, pruritic hyperpigmented papules distributed over the trunk and limbs, and chronic diarrhoea. He had eosinophilia, low haemoglobin and serum IgE levels, and raised erythrocyte sedimentation rate. Histopathology of the leg ulcer was consistent with the diagnosis of PG, while the histology of the hyperpigmented papule revealed tissue eosinophilia. Subsequent evaluation was conclusive of the diagnosis of PG, idiopathic hypereosinophilic syndrome (IHES) and selective IgE deficiency. Dexamethasone pulse therapy achieved resolution of the ulcer and reduction in the eosinophilia. Further evaluation for the persistent diarrhoea led to a diagnosis of lymphocytic colitis (LC), which responded to budesonide. To our knowledge, the association of PG with IHES, selective IgE deficiency or LC has not been previously reported. © 2015 British Association of Dermatologists.

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

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

2013-03-01

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

Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review.

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van Tilburg, C M; Sanders, E A M; Rovers, M M; Wolfs, T F W; Bierings, M B

2006-10-01

Intensified chemotherapy regimens resulting in improved survival of children with acute lymphocytic leukemia (ALL) lead to concerns about therapy-induced immune damage reflected by the loss of protection of previous immunizations and the efficacy of (re-)vaccination. The severity of secondary immunodeficiency, however, is not clear and knowledge is based on a limited number of studies. We performed a systematic review on literature concerning vaccination data of children with ALL published since 1980. Eight studies fulfilled the inclusion criteria. Regarding antibody titers after treatment, the number of children who had preserved the defined protection level for antibodies differed widely, ranging from 17 to 98% for diphtheria, 27 to 82% for Bordetella pertussis, 20 to 98% for tetanus, 62 to 100% for poliomyelitis, 35 to 100% for Haemophilus influenzae type B (HiB), 29 to 92% for mumps, 29 to 60% for measles and 72 to 92% for rubella. Most patients however responded to revaccination, demonstrating immunological recovery. Although the designs and results of the included studies varied widely, it can be concluded that cytostatic therapy for ALL in children results in a temporarily reduction of specific antibody levels. Memory is preserved but revaccination may be warranted. This is the first systematic review and the best possible current approximation of chemotherapy-induced immune damage in children after ALL treatment.

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

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

2016-10-01

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

Normal villous architecture with increased intraepithelial lymphocytes: a duodenal manifestation of Crohn disease.

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Patterson, Emily R; Shmidt, Eugenia; Oxentenko, Amy S; Enders, Felicity T; Smyrk, Thomas C

2015-03-01

To assess a possible association between inflammatory bowel disease (IBD) and the histologic finding in duodenal biopsy specimens of increased intraepithelial lymphocytes (IELs) with normal villous architecture. We identified all patients with duodenal biopsy specimens obtained between 2000 and 2010 showing increased IELs and normal architecture. Among the 74 such patients who also had IBD, we characterized the clinical features of IBD and reviewed all available upper gastrointestinal biopsy specimens. Fifty-eight patients had Crohn disease, 13 had ulcerative colitis, and three had IBD, type unclassified. No duodenal sample with increased IELs had other histologic features of IBD. Among gastric biopsy specimens from 34 patients with Crohn disease, nearly half (16) had focal gastritis. We propose that Crohn disease be included in the differential diagnosis for increased IELs with normal villous architecture in duodenal biopsy specimens, particularly when gastric biopsy specimens show focal gastritis. Copyright© by the American Society for Clinical Pathology.

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

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

2017-09-01

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

Mucosal healing in ulcerative colitis

DEFF Research Database (Denmark)

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

2013-01-01

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

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

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Wei Zhang

2016-04-01

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

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

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

2001-05-01

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

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

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Lakatos, Peter-Laszlo; Lakatos, Laszlo

2008-07-07

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

Tratamientos más utilizados en la colitis ulcerativa

OpenAIRE

Daisy Carbajal-Quintana

2015-01-01

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

Therapeutic action of ghrelin in a mouse model of colitis.

Science.gov (United States)

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

2006-05-01

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

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

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Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

2015-11-15

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. Copyright © 2015 the American Physiological Society.

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

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Kirchgessner Annette

2011-08-01

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

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

OpenAIRE

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

OpenAIRE

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

2016-01-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Nitric oxide and chronic colitis

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Matthew B Grisham

1996-01-01

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

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

DEFF Research Database (Denmark)

Kjellev, Stine; Thim, Lars; Pyke, Charles

2007-01-01

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

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

DEFF Research Database (Denmark)

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

2012-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

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

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

2015-11-06

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

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

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

1999-01-01

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

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

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

2017-09-26

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

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Su-Min Lim

2016-01-01

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

Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

Science.gov (United States)

Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

2016-04-01

Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

The Increased Expression of CCL20 and CCR6 in Rectal Mucosa Correlated to Severe Inflammation in Pediatric Ulcerative Colitis

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Keiichi Uchida

2015-01-01

Full Text Available Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC, <16 years old, n=24 and adult-onset UC (AUC, ≧16 years old, n=117. A total of 141 formalin-fixed, paraffin-embedded tissue samples of rectum were obtained from these patients. Histological inflammation of rectum in resected specimen was evaluated by using Geboes histological assessment. In immunohistochemistry study, the CCL20 expression was evaluated by intensity and the stained area, and the CCR6 expression was evaluated by lymphocytes infiltration pattern. Results. CCL20 score and CCR6 positive lymphocytes infiltration pattern were statistically significantly correlated with histological inflammation severity of UC in all patients (P<0.05. CCL20 and CCR6 expression in CUC were statistically significantly higher than that in AUC in all or pathologically severe cases (P<0.05. Conclusions. CCL20 and CCR6 may play a significant role in local damage and pathological changes in UC especially pediatric patients. In the future, our understanding of the differences in CCL-CCR6 interaction between adults and children may lead to the pathogenesis of IBD.

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

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Bruno César da Silva

2015-01-01

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

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

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Ahmed M Hassan

2014-11-01

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

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

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

2015-09-30

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

Biodistribution of radiolabeled lymphocytes

International Nuclear Information System (INIS)

Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

1985-01-01

Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

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

LENUS (Irish Health Repository)

McDermott, Edel

2013-03-01

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

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

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

2015-12-30

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

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

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Chad K Heazlewood

2008-03-01

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

Ischemic colitis or melanosis coli: a case report

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Nadeem Mohammed

2007-09-01

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

Ischemic colitis after mesotherapy combined with anti-obesity medications.

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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.

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

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

1996-07-01

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

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

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Mark G Swain

1991-01-01

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

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

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

2018-02-27

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

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

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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...

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

DEFF Research Database (Denmark)

Pedersen, G.; Brynskov, Jørn

2010-01-01

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

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

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Willis Cynthia R

2012-10-01

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

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

OpenAIRE

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

1995-01-01

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

Effect of Vibrio cholerae neuraminidase on the mitogen response of T lymphocytes. I. Enhancement of macrophage T-lymphocyte cooperation in concanavalin-A-induced lymphocyte activation.

Science.gov (United States)

Knop, J

1980-12-01

Vibrio cholerae neuraminidase (VCN) enhances the immune response of lymphocytes in various systems, such as antigen- and mitogen-induced blastogenesis, mixed lymphocyte culture (MLC) and tumor-cell response. We used macrophage-depleted and reconstituted murine lymph-node T-cells to investigate the effect of VCN on macrophage-T-lymphocyte co-operation in Con-A-induced lymphocyte activation. In unfractionated lymph-node cells VCN enhanced the Con-A-induced lymphocyte activation as measured by 3H-thymidine (3H-dThd) incorporation. Removing macrophages from the cells resulted in a significantly diminished response. In addition the enhancing effect of VCN was greatly reduced. Reconstitution of the lymphocyte cultures with macrophages in increasing numbers and from various sources rstored the lymphocyte response and the enhancing effect of VCN. VCN proved to be most efficient in cultures reconstituted with normal peritoneal macrophages. Some effect was also observed using bone-marrow-derived (BM) macrophages. However, higher numbers of normal PE macrophages in the presence of VCN inhibited lymphocyte activation, and inhibition by thioglycollate-broth-induced macrophages was considerably increased by VCN. These results suggest that VCN acts by increasing the efficiency of macrophage-T lymphocyte interaction.

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

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

2017-05-01

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

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

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

2012-01-01

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

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

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Gupta R

2014-01-01

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

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

DEFF Research Database (Denmark)

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

2017-01-01

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

Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Science.gov (United States)

2018-01-26

Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

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

LENUS (Irish Health Repository)

Shanahan, F

2012-02-03

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

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

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Vincenzo Villanacci

2011-07-01

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

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

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Collins, Hampton W; Frye, Jeanetta W

2018-01-01

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

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

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Barrett, Kim E; McCole, Declan F

2016-11-01

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

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

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

2011-10-01

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

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

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

2015-07-01

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

Discrimination of human cytotoxic lymphocytes from regulatory and B-lymphocytes by orthogonal light scattering

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; de Grooth, B.G.; ten Napel, C.H.H.; van Berkel, W.; Greve, Jan

1986-01-01

Light scattering properties of human lymphocyte subpopulations selected by immunofluorescence were studied with a flow cytometer. Regulatory and B-lymphocytes showed a low orthogonal light scatter signal, whereas cytotoxic lymphocytes identified with leu-7, leu-11 and leu-15 revealed a large

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

OpenAIRE

Broomé, U; Glaumann, H; Hultcrantz, R

1990-01-01

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

Burden of Ulcerative Colitis on Functioning and Well-being: A Systematic Literature Review of the SF-36® Health Survey.

Science.gov (United States)

Yarlas, Aaron; Rubin, David T; Panés, Julian; Lindsay, James O; Vermeire, Séverine; Bayliss, Martha; Cappelleri, Joseph C; Maher, Stephen; Bushmakin, Andrew G; Chen, Lea Ann; DiBonaventura, Marco

2018-04-27

This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal pouch-anal anastomosis, along with respective reference samples. Clinically meaningful burden was observed in samples with active or mixed disease activity [deficits: PCS = 5.6, MCS = 5.5] on all SF-36 domains except Physical Functioning. No burden was observed in samples in remission or post-surgical patients [deficits: PCS = 0.8, MCS = 0.4] except for the General Health perception domain. Patients with active UC experience a clinically meaningful burden of disease across most aspects of quality of life. Patients with inactive UC exhibit negligible disease burden and are comparable to the general population on most quality-of-life outcomes. Thus, treatments which effectively induce and maintain remission may restore physical and mental health status.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-11-12

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

Ischemic colitis in five points: an update 2013.

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

2014-05-01

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

Methotrexate in the treatment of peripheral arthritis in ulcerative colitis

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R. Scarpa

2011-06-01

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

Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

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Caimi Luigi

2010-11-01

Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

Selenoprotein P in colitis-associated carcinoma

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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

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

Science.gov (United States)

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

2015-05-27

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

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

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Nicolette W Duijvis

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

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

International Nuclear Information System (INIS)

Song Qingzhang; Zhang Min

2010-01-01

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

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

LENUS (Irish Health Repository)

Veerappan, Sundaram G

2012-02-01

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

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

OpenAIRE

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

2016-01-01

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

Processed coffee alleviates DSS-induced colitis in mice

Directory of Open Access Journals (Sweden)

Bernd L. Fiebich

2013-05-01

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

Golimumab for the treatment of ulcerative colitis

NARCIS (Netherlands)

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

2014-01-01

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

Surgery for Crohn's Disease and Ulcerative Colitis

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

Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

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Valerie A. Allen

2016-01-01

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

Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

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Kyu Hwan Kwack

2017-01-01

Full Text Available We have examined the effect of progranulin (PGRN on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-β.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

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F. Cozzi

2011-09-01

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

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

Science.gov (United States)

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

2016-09-30

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

Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

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Yutaro Shiota

2000-01-01

Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

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

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

2018-03-01

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

Golimumab for moderate to severe ulcerative colitis

NARCIS (Netherlands)

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

2017-01-01

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

Susceptibility to Entamoeba histolytica intestinal infection is related to reduction in natural killer T-lymphocytes in C57BL/6 mice

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Fabrício M.S. Oliveira

2012-04-01

Full Text Available Entamoeba histolytica is a protozoan that causes amoebiasis. Recent studies demonstrated that natural killer T lymphocytes (NKT are critical for preventing the development of amoebic liver abscess. In spite of that, there are only a handful of studies in the area. Herein, we explored the role of NKT cells in E. histolytica infection using C57BL/6 wild-type and CD1-/- mice. Animals were inoculated with E. histolytica and sacrificed 48 hours later to collect caecum samples that were used for quantitative analyses of lesions, trophozoites, NK1.1+ T lymphocytes and expression of the mucus protein MUC-2 by immunohistochemistry technique. Quantitative analyses confirmed that the frequency of NK1.1+ T cells was significantly lower in samples from C57BL/6 CD1-/- mice as compared to their wild type (WT counterparts. The extension of necrotic mucosa was larger and the number of trophozoites higher in Entamoeba (Eh-infected CD1-/- mice when compared with Eh-infected WT mice. In mice from both groups, noninfected (CTRL and Eh-infected CD1-/-, there was a reduction in the thickness of the caecal mucosa and in the MUC-2-stained area in comparison with CTRL- and Eh-WT mice. Our results showed that NKT lymphocytes contribute to resistance against Entamoeba histolytica infection and to the control of inflammation in the colitis induced by infection. The presence of a normal epithelial layer containing appropriate levels of mucus had also a protective role against infection.

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

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José Wander BREGANÓ

2014-09-01

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

[Aseptic cutaneous breast abscesses associated with ulcerative colitis].

Science.gov (United States)

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

2016-02-01

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

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

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F. Bermejo

2004-02-01

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

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

Science.gov (United States)

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

2014-09-01

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

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

Science.gov (United States)

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

2016-01-01

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

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

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

OpenAIRE

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

2017-01-01

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

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

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Barrett, Kim E.; McCole, Declan F.

2016-01-01

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

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

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Angelo Zullo

2011-01-01

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

Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders

DEFF Research Database (Denmark)

Perner, Anders; Rask-Madsen, J

1999-01-01

The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular...... impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases. A variety of proinflammatory mediators, including tumour necrosis factor alpha, interleukin-1beta, interferon gamma, leukotriene B4 and platelet activating factor, promote the adherence...

Review article

DEFF Research Database (Denmark)

Perner, A; Rask-Madsen, J

1999-01-01

The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular...... impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases. A variety of proinflammatory mediators, including tumour necrosis factor alpha, interleukin-1beta, interferon gamma, leukotriene B4 and platelet activating factor, promote the adherence...

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

Science.gov (United States)

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

2014-01-01

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

Microarray Assisted Gene Discovery in Ulcerative Colitis

DEFF Research Database (Denmark)

Brusgaard, Klaus

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

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Oral Tolerance: A New Tool for the Treatment of Gastrointestinal Inflammatory Disorders and Liver-Directed Gene Therapy

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Yaron Ilan

1999-01-01

Full Text Available Oral tolerance is a method of downregulating an immune response by feeding antigens. The use of oral tolerance toward adenoviruses and colitis-extracted proteins for long term gene therapy and alleviation of experimental colitis, and the mechanisms of tolerance induction are presented. Adenoviruses are efficient vectors in liver-directed gene therapy; however, the antiviral immune response precludes the ability to achieve long term gene expression and prohibits the ability to reinject the recombinant virus. Oral tolerance induction via feeding of viral-extracted proteins prevented the antiadenoviral humoral and cellular immune responses, thus enabling long term gene therapy using these viruses. Moreover, pre-existing immune response to the virus was overcome by tolerance induction, enabling prolonged gene expression in a presensitized host. Inflammatory bowel diseases are immune-mediated disorders where an imbalance between proinflammatory (T helper cell type 1 and anti-inflammatory (T helper cell type 2 cytokines are thought to play a role in the pathogenesis. In the experimental colitis model, the feeding of colitis-extracted proteins downregulated the anticolon immune response. Tolerance induction toward colitis-extracted proteins ameliorated colonic inflammation as shown by decreased diarrhea and reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness and edema. Histological parameters for colitis were markedly improved in tolerized animals. In both models, tolerized animals developed an increase in transforming growth factor-beta, interleukin-4 and interleukin-10, and a decrease in the mRNA of interferon-gamma lymphocytes and serum levels. Adoptive transfer of tolerized lymphocytes enabled the transfer of tolerance toward adenoviruses and colon-extracted proteins. Thus, oral tolerance induces suppressor lymphocytes that mediate immune response downregulation by induction of a shift from a proinflammatory T

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

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

2016-09-01

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

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

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

2017-06-01

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

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

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

2017-11-01

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

Ischemic Colitis after Weight-Loss Medication

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Dan Comay

2003-01-01

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

Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.

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Ng, Siew C; Shi, Hai Yun; Hamidi, Nima; Underwood, Fox E; Tang, Whitney; Benchimol, Eric I; Panaccione, Remo; Ghosh, Subrata; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y; Kaplan, Gilaad G

2018-12-23

Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI. We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8-17·8] and APC for ulcerative colitis +14·9% [10·4-19·6]) and Taiwan (APC

Lymphocyte-platelet crosstalk in Graves' disease.

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Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

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

LENUS (Irish Health Repository)

Bambury, Niamh

2012-02-03

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

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

DEFF Research Database (Denmark)

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

2012-01-01

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

A Systematic Review of the Cost-Effectiveness of Biologics for Ulcerative Colitis.

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Stawowczyk, Ewa; Kawalec, Paweł

2018-04-01

Ulcerative colitis (UC) is a chronic autoimmune inflammation of the colon. The condition significantly decreases quality of life and generates a substantial economic burden for healthcare payers, patients and the society in which they live. Some patients require chronic pharmacotherapy, and access to novel biologic drugs might be crucial for long-term remission. The analyses of cost-effectiveness for biologic drugs are necessary to assess their efficiency and provide the best available drugs to patients. Our aim was to collect and assess the quality of economic analyses carried out for biologic agents used in the treatment of UC, as well as to summarize evidence on the drivers of cost-effectiveness and evaluate the transferability and generalizability of conclusions. A systematic database review was conducted using MEDLINE (via PubMed), EMBASE, Cost-Effectiveness Analysis Registry and CRD0. Both authors independently reviewed the identified articles to determine their eligibility for final review. Hand searching of references in collected papers was also performed to find any relevant articles. The reporting quality of economic analyses included was evaluated by two reviewers using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We reviewed the sensitivity analyses in cost-effectiveness analyses to identify the variables that may have changed the conclusions of the study. Key drivers of cost-effectiveness were selected by identifying uncertain parameters that caused the highest change of the results of the analyses compared with base-case results. Of the 576 identified records, 87 were excluded as duplicates and 16 studies were included in the final review; evaluations for Canada, the UK and Poland were mostly performed. The majority of the evaluations revealed were performed for infliximab (approximately 75% of total volume); however, some

Collagenous colitis: histopathology and clinical course.

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

1997-01-01

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

Pulmonary Function in Ulcerative Colitis

OpenAIRE

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

2008-01-01

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

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

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

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

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Anna Pérez-Bosque

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

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

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

2017-01-01

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

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

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

2018-03-01

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

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

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Wang D

2013-03-01

Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

Ulcerative Colitis in Colonic Interposition for Esophageal Atresia

OpenAIRE

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

2016-01-01

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

Chronic lymphocytic leukemia (CLL)

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... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

Evolution and phylogeny of B lymphocytes

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Fabiola Claudio-Piedras

2016-05-01

Full Text Available B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

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

KAUST Repository

Arsenescu, Violeta

2011-04-11

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

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

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Li-Na Zhao

Full Text Available BACKGROUND: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. METHODS: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI. Publication bias and heterogeneity were assessed. RESULTS: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84. Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. CONCLUSION: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

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

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

2011-12-01

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

Successful Use of Adalimumab for Treating Pyoderma Gangrenosum with Ulcerative Colitis under Corticosteroid-tapering Conditions.

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Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Nagai, Kenta; Hayashi, Ryohei; Chayama, Kazuaki

2015-01-01

A 52-year-old woman with ulcerative colitis was admitted to our hospital for an ulcerative colitis flare-up under salazosulfapyridine therapy. The symptoms improved with high-dose corticosteroids. After prednisolone was tapered to 10 mg, the frequency of diarrhea increased. The diarrhea was accompanied by joint pain and a skin ulcer with abscess formation, which was diagnosed to be pyoderma gangrenosum. The patient was started on adalimumab. A positive response to the adalimumab therapy was observed after 2 weeks, during which time the ulcerative skin lesion healed completely, however, colonic mucosal healing was achieved at 2 months. Therefore, adalimumab appears to be an effective therapeutic option for patients with ulcerative colitis-associated pyoderma gangrenosum.

The Next Generation of Targeted Molecules for the Treatment of Chronic Lymphocytic Leukemia.

Science.gov (United States)

Jeyakumar, Deepa; O'Brien, Susan

2016-11-15

With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy. As a class of medications, B-cell receptor inhibitors have some unique side effects, including redistribution lymphocytosis. Toxicities associated specifically with ibrutinib include increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities: transaminitis, colitis, and pneumonitis. Targeted therapies recently approved for use in CLL include the novel anti-CD20 monoclonal antibodies obinutuzumab and ofatumumab, and the B-cell lymphoma 2 inhibitor venetoclax. This article describes the clinical data that led to approval of these B-cell receptor inhibitors for the treatment of CLL, and highlights newer agents in clinical development that target the same kinases as the currently available therapies.

Dextran sulfate sodium-induced colitis in piglets

DEFF Research Database (Denmark)

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

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

Clostridium difficile Infection Worsens the Prognosis of Ulcerative Colitis

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María E Negrón

2014-01-01

Full Text Available BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients.

A case of obstructive colitis caused by rectal stenosis and adhesion due to irradiation

International Nuclear Information System (INIS)

Tochika, Naoshige; Sugimoto, Takeki; Takano, Atsushi; Kobayashi, Michiya; Matsuura, Kimio; Araki, Keijiro

2000-01-01

We report a case of obstructive colitis associated with rectal stenosis and adhesion due to irradiation. A 68-year-old woman who had been suffering from constipation after an episode of irradiation for cervical cancer of the uterus two years previously was admitted to our hospital complaining of the lower abdominal pain. After two days, an operation was performed under a diagnosis or panperitonitis. Stenosis and adhesion of the rectum and necrosis at the oral side of the adhesion was recognized. Histologically, necrosis of the rectum from mucosa to serosa was recognized, and no neoplastic change was seen at the stenotic portion. The most common cause of local stenosis of the colon leading to obstructive colitis is colon cancer. Obstructive colitis caused by a benign stenosis as reported here is rare. (author)

A case of obstructive colitis caused by rectal stenosis and adhesion due to irradiation

Energy Technology Data Exchange (ETDEWEB)

Tochika, Naoshige; Sugimoto, Takeki; Takano, Atsushi; Kobayashi, Michiya; Matsuura, Kimio; Araki, Keijiro [Kochi Medical School, Nankoku (Japan)

2000-03-01

We report a case of obstructive colitis associated with rectal stenosis and adhesion due to irradiation. A 68-year-old woman who had been suffering from constipation after an episode of irradiation for cervical cancer of the uterus two years previously was admitted to our hospital complaining of the lower abdominal pain. After two days, an operation was performed under a diagnosis or panperitonitis. Stenosis and adhesion of the rectum and necrosis at the oral side of the adhesion was recognized. Histologically, necrosis of the rectum from mucosa to serosa was recognized, and no neoplastic change was seen at the stenotic portion. The most common cause of local stenosis of the colon leading to obstructive colitis is colon cancer. Obstructive colitis caused by a benign stenosis as reported here is rare. (author)

Early manifestation of Yersinia colitis demonstrated by the double-contrast barium enema

Energy Technology Data Exchange (ETDEWEB)

Aspestrand, F.

1986-11-01

A 19-year old female with a bloody, diarrheal illness of acute onset where Crohn's disease primarly was suspected is presented. The double-contrast barium enema revealed multiple, diffusely scattered aphthous erosions of the colonic mucosa: the rectum was scarcely affected. Biopsies taken by endoscopy demonstrated nonspecific inflammatory changes of the mucous membrane. However, routinely taken stool cultures revealed an infectious colitis due to Yersinia enterocolitica. Our case demonstrates the necessity to consider Yersinia enterocolitis in the radiographic differential diagnosis when the diagnosis of Crohn's disease or ulcerative colitis seems obvious.

Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis.

Science.gov (United States)

Lagishetty, Venu; Misharin, Alexander V; Liu, Nancy Q; Lisse, Thomas S; Chun, Rene F; Ouyang, Yi; McLachlan, Sandra M; Adams, John S; Hewison, Martin

2010-06-01

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

Science.gov (United States)

Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

2016-11-01

This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

To the nucleolar bodies (nucleoli) in cells of the lymphocytic lineage in patients suffering from B - chronic lymphocytic leukemia.

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Smetana, K; Karban, J; Trneny, M

2010-01-01

The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

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Alexandra Wagnerova

2017-01-01

Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

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

Science.gov (United States)

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

2008-05-06

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

Radiation sensitivity of human malignant lymphocytes

International Nuclear Information System (INIS)

Seshadri, R.; Matthews, C.; Morley, A.A.

1985-01-01

A simple and rapid in vitro technique to assess the sensitivity of human malignant lymphocytes to roentgen irradiation is described. A variety of established malignant lymphocyte cell lines were cloned in microwells and clone survival was used as the end-point. The survival of the clonogenic malignant lymphocyte down to a fraction of approximately 0.001 could be measured accurately. Except for a T-cell line, the radiation sensitivities of the cell lines were similar to that of normal T-lymphocytes. (orig.)

A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review.

Science.gov (United States)

Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

2017-10-01

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

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

Science.gov (United States)

Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

2014-01-01

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

A Limited Role of p53 on the Ability of a Hexane Fraction of American Ginseng to Suppress Mouse Colitis

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Deepak Poudyal

2012-01-01

Full Text Available Ulcerative colitis (UC is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG, and to a greater extent, a Hexane fraction of AG (HAG can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo. Finally, we asked whether HAG could cause cell cycle arrest of HCT116 colon cancer cells in vitro. Interestingly, HAG caused a G1 arrest of such cells independent of p53 status. Findings are significant because HAG suppresses colitis and associated colon cancer, and mutation in p53 is observed in most colitis-driven colon cancers. Therefore, HAG might be very effective in targeting the inflammatory cells and cancer cells since it induces apoptosis of inflammatory cells and cell cycle arrest in both p53−/− and WT p53 colon cancer cells.

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

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Naeem M

2015-07-01

Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Kissow, Hannelouise; Hare, Kristine

2005-01-01

% dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg......2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score...... in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer....

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

Energy Technology Data Exchange (ETDEWEB)

Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

2013-08-15

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

AOM/DSS Model of Colitis-Associated Cancer

Science.gov (United States)

Parang, Bobak; Barret, Caitlyn W.; Williams, Christopher S.

2016-01-01

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

AOM/DSS Model of Colitis-Associated Cancer.

Science.gov (United States)

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

2016-01-01

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

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

International Nuclear Information System (INIS)

Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

2015-01-01

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys 3 ]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

2015-02-27

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators.

Science.gov (United States)

Kannan, Narayanan; Guruvayoorappan, Chandrasekharan

2013-05-01

Inflammatory bowel diseases (IBD), including Crohn's disease and Ulcerative colitis (UC), are life-long and recurrent disorders of the gastrointestinal tract with unknown etiology. The present study is designed to evaluate the ameliorative effect of Bauhinia tomentosa during ulcerative colitis (UC). Three groups of animals (n=6) were treated with B. tomentosa (5, 10, 20 mg/kg B.wt respectively) for 5 consecutive days before induction of UC. UC was induced by intracolonic injection of 3% acetic acid. The colonic mucosal injury was assessed by macroscopic scoring and histological examination. Furthermore, the mucosal content of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide (NO), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity confirms that B. tomentosa could significantly inhibit colitis in a dose dependent manner. The myeloperoxidase (MPO), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS) expression studies and lactate dehydrogenase (LDH) assay also supported that B. tomentosa could significantly inhibit experimental colitis. The effect was comparable to the standard drug sulfasalazine. Colonic mucosal injury parallels with the result of histological and biochemical evaluations. The extracts obtained from B. tomentosa possess active substances, which exert marked protective effects in acute experimental colitis, possibly by regulating the antioxidant and inflammatory mediators. Copyright © 2013 Elsevier B.V. All rights reserved.

Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

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Jing Zhang

Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

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

Directory of Open Access Journals (Sweden)

Laura P Hale

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

Protective Effect of Laminaria japonica with Probiotics on Murine Colitis

Directory of Open Access Journals (Sweden)

Seok-Jae Ko

2014-01-01

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

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

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Lifu Wang

2017-09-01

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

Opinion: Interactions of innate and adaptive lymphocytes

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Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

Periostal hypertrophic osteopathy of bones (long bones) in colitis ulcerosa in adolescents

International Nuclear Information System (INIS)

Bargon, G.; Arlart, I.

1982-01-01

The article reports on a 14-year old girl with periostal new formation of bones at the long bones of the lower arms, the femora and the lower legs the individual phalanges and metacarpalia after colitis ulcerosa which had lasted for several years and had progressed stagewise. After a clinically recorded new attack the periostal new formations of bone progressed. Some time after the last attack of colitis the periostal changes in the bones partially receded. The article discusses the hypothetic explanations aiming at interpreting the pathogenesis of hypertrophic osteoarthropathies and periostoses, as given in the literature. (orig.) [de

Periostal hypertrophic osteopathy of bones (long bones) in colitis ulcerosa in adolescents

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Bargon, G.; Arlart, I.

1982-03-01

The article reports on a 14-year old girl with periostal new formation of bones at the long bones of the lower arms, the femora and the lower legs the individual phalanges and metacarpalia after colitis ulcerosa which had lasted for several years and had progressed stagewise. After a clinically recorded new attack the periostal new formations of bone progressed. Some time after the last attack of colitis the periostal changes in the bones partially receded. The article discusses the hypothetic explanations aiming at interpreting the pathogenesis of hypertrophic osteoarthropathies and periostoses, as given in the literature.

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

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Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

2017-05-04

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (Ptofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (Ptofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. In patients with moderately to severely

Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

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Keulemans, Y C; Mok, K S; Slors, J F; Brink, M A; Gouma, D J; Tytgat, G N; Groen, A K

1999-10-01

Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

Location and activity of ulcerative and Crohn's colitis by 111In leukocyte scan. A prospective comparison study

International Nuclear Information System (INIS)

Stein, D.T.; Gray, G.M.; Gregory, P.B.; Anderson, M.; Goodwin, D.A.; McDougall, I.R.

1983-01-01

A prospective blinded study comparing the 111 In leukocyte scan to barium enema, colonoscopy, or surgery or a combination of these, was carried out in 15 patients (10 with active ulcerative colitis and 5 with active Crohn's colitis). Correlation of disease location to colonic regions between indium scan and other diagnostic studies was excellent in 11 instances, good in 2, and poor in 3. In 2 of the 3 studies where major disagreement occurred, the comparative barium enema was performed greater than 2 mo after the indium scan. Disease activity, estimated by the intensity of radionuclide uptake, was compared to clinical disease activity assessed by the Crohn's Disease Activity Index for both forms of colitis. The relative degree of inflammation estimated by the indium scan correlated well with the independent clinical assessment (correlation coefficient . 0.81). The indium 111 leukocyte scan appears to be an accurate, noninvasive method for assessing the extent and the severity of the inflammation in patients with acute ulcerative or Crohn's colitis

The Role of Syndrome Differentiation in the Clinical Efficacy of Punica Granatum on Patients with Ulcerative Colitis.

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Kamali, Mohammadali; Khodadoost, Mahmoud; Tavakoli, Hamid; Kamalinejad, Mohammad; Gachkar, Latif; Adibi, Payman; Heydari, Mojtaba

2016-05-01

The present study investigated the difference between therapeutic responses of hot and cold temperament patients (based on traditional Persian medicine) with ulcerative colitis to pomegranate peel extract. Seventy-eight patients with moderate ulcerative colitis based on Lichtiger Colitis Activity Index (LCAI) criteria were randomized to receive an aqueous extract of the Punica granatum peel (6 gram per day) or placebo for four weeks. They were assessed before and after the intervention in terms of symptoms by LCAI scoring system. The results were compared in two therapeutic groups based on the patient s' temperament (cold and hot) which were diagnosed based on a previously validated questionnaire. Therapeutic response was significantly higher in patients with hot temperament compared to patients with cold temperament in the P. granatum group (1.91±0.492 vs. -0.500±0.500, P=0.029). This study showed the importance of considering syndrome differentiation and temperament in interpreting the effect of P. granatum peel extract on ulcerative colitis.

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

NARCIS (Netherlands)

Sandborn, William J.; Su, Chinyu; Sands, Bruce E.; D'Haens, Geert R.; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G.; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

2017-01-01

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized,

Ischemic Colitis in an Endurance Runner

Directory of Open Access Journals (Sweden)

Chase Grames

2012-01-01

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

Neutrophil to lymphocyte with monocyte to lymphocyte ratio and white blood cell count in prediction of lung cancer

Directory of Open Access Journals (Sweden)

Thang Thanh Phan

2018-04-01

Full Text Available Background Lung cancer is the most common cause of cancer deaths in both sexes, while it is very difficult for screenings and early detection. Aims This study aims to clarify the role of systematic inflammation markers, including white blood cell (WBC, neutrophil (NEU, monocyte (MONO, platelet (PLT, neutrophil to lymphocyte ratio (NLR, monocyte to lymphocyte ratio (MLR and platelet to lymphocyte ratio (PLR in prediction of lung cancer. Methods A case-control study was conducted on 1,315 primary lung cancer patients and 1,315 healthy adults with matched age and gender at Cho Ray hospital. NLR, MLR and PLR were calculated by using neutrophil, lymphocyte, monocyte and platelet count which were recalled from laboratory database. With 600 cases in the derivation set, the logistic regression with univariate analysis was used to identify the impacted marker, then developing the optimal prediction model for lung cancer by logistic regression with multivariate method. The diagnostic values of optimal model consisting of sensitivity (Sen, specificity (Spe, positive predictive value (PPV, negative predictive value (NPV and the area under the ROC curve (AUC value were extracted and verified on all data, in validation set. Results The median values of WBC, NEU, MONO, PLT, NLR, MLR and PLR in lung cancer were not significantly difference between histological subtypes and clinical stages (p > 0.05, but higher than the values in control group (p < 0.01. Multivariates analysis shows that NLR, MLR and WBC were three parameters that have the significant impact of the optimal prediction model (p < 0.01. The AUC value, sensitivity and specificity of the optimal model for lung cancer detection were 0.881, 73.5 per cent (95 per cent CI:70.3–76.6 and 87.7 per cent (95 per centCI:85.2–89.9, respectively. Whereas, the PPV and NPV values of prediction model were 85.7 per cent (95 per cent CI:82.8–88.2 and 76.8 (95 per centCI:73.9–79.5, respectively. Among three

Ulcerative colitis: criteria and methods of prognosis of exacerbation

Directory of Open Access Journals (Sweden)

Kashkina E.l.

2014-09-01

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

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

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

2018-01-01

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

Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE) : relation to lymphocyte activation and disease activity

NARCIS (Netherlands)

Bijl, M; Horst, G; Limburg, PC; Kallenberg, CGM

2001-01-01

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production, Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased Susceptibility to Fas-mediated apoptosis in

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

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

2013-01-01

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

Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis.

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Rahimian, Reza; Zirak, Mohammad Reza; Keshavarz, Mojtaba; Fakhraei, Nahid; Mohammadi-Farani, Ahmad; Hamdi, Hanan; Mousavizadeh, Kazem

2016-09-20

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT 3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1β diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ and decreased the MPO activity (p < .05). Tropisetron exerts notable anti-inflammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPARγ receptors.

Dietary α-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice.

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Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M; Berman-Booty, Lisa D; Galley, Jeffrey D; Chitchumroonchokchai, Chureeporn; Mace, Thomas; Suksamrarn, Sunit; Bailey, Michael T; Clinton, Steven K; Lesinski, Gregory B; Failla, Mark L

2014-06-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of dietary isoflavone intake on gastrointestinal symptoms in ulcerative colitis individuals in remission.

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Głąbska, Dominika; Guzek, Dominika; Grudzińska, Dominika; Lech, Gustaw

2017-08-07

To analyse the association between isoflavone intake and ulcerative colitis motility symptoms in individuals in remission. Cross-sectional study was conducted in a group of ulcerative colitis remission individuals, in sub-groups characterised by various intestinal motility and functioning characteristics (abdominal pain, flatulence, constipations, tenesmus). Total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. Assessment of diet was based on self-reported data from each patient's dietary records taken over a period of three typical, random days (2 weekdays and 1 d of the weekend). The daily isoflavone intake (daidzein, genistein, glycitein and total isoflavones) and daily isoflavone intake per 1000 kcal of diet were assessed. No correlations between isoflavone intake levels and number of bowel movements per day were observed both in the case of intake and intake per 1000 kcal of diet. In the group of individuals declaring lack of abdominal pain, the higher intakes of daidzein ( P = 0.0075), daidzein per 1000 kcal of diet ( P = 0.0358) and total isoflavone ( P = 0.0358) were stated, than in the group of individuals declaring abdominal pain. In the group of individuals declaring lack of constipations, the lower intakes of glycitein ( P = 0.0213) and glycitein per 1000 kcal of diet ( P = 0.0213) were stated, than in the group of individuals declaring presence of constipations. No differences were observed in isoflavone intake between groups of ulcerative colitis individuals declaring lack of flatulence and declaring presence of flatulence, as well as between groups declaring lack of tenesmus and declaring presence of tenesmus. The moderate dietary isoflavone intake may be beneficial for individuals with ulcerative colitis in remission, however, before including it into recommendations, further prospective studies are needed.

Fæcestransplantation som behandling af Clostridium difficile-infektion, colitis ulcerosa og metabolisk syndrom

DEFF Research Database (Denmark)

Carstensen, Jeppe West; Hansen, Axel Kornerup

2014-01-01

Faecal transplantation as a treatment for Clostridium difficile infection, ulcerative colitis and the metabolic syndrome Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial......, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal...... transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection....

The early manifestation of Yersinia colitis demonstrated by the double-contrast barium enema

International Nuclear Information System (INIS)

Aspestrand, F.

1986-01-01

A 19-year old female with a bloody, diarrheal illness of acute onset where Crohn's disease primarly was suspected is presented. The double-contrast barium enema revealed multiple, diffusely scattered aphthous erosions of the colonic mucosa: the rectum was scarcely affected. Biopsies taken by endoscopy demonstrated nonspecific inflammatory changes of the mucous membrane. However, routinely taken stool cultures revealed an infectious colitis due to Yersinia enterocolitica. Our case demonstrates the necessity to consider Yersinia enterocolitis in the radiographic differential diagnosis when the diagnosis of Crohn's disease or ulcerative colitis seems obvious. (orig.) [de

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

Science.gov (United States)

Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

2010-02-01

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor

Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis

DEFF Research Database (Denmark)

Hillingsø, J G; Kjeldsen, J; Schmidt, P T

2002-01-01

BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous...... B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after......: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics....

An update on anti-TNF agents in ulcerative colitis

NARCIS (Netherlands)

Samaan, Mark A.; Bagi, Preet; Vande Casteele, Niels; D'Haens, Geert R.; Levesque, Barrett G.

2014-01-01

Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their

Organ distribution of 111In-oxine labeled lymphocytes in normal subjects and in patients with chronic lymphocytic leukemia and malignant lymphoma

International Nuclear Information System (INIS)

Matsuda, Shin; Uchida, Tatsumi; Yui, Tokuo; Kariyone, Shigeo

1982-01-01

T and B lymphocyte survival and organ distribution were studied by using 111 In-oxine labeled autologous lymphocytes in 3 normal subjects, 3 patients with chronic lymphocytic leukemia (CLL) and 9 with malignant lymphoma (ML).FDisappearance curves of the labeled lymphocytes showed two exponential components in all cases. The half time of the first component was within 1 hour in all cases. That of the second one was 50.7 +- 6.4 hours for all lymphocytes, 52.0 +- 5.5 hours for T lymphocytes and 31.6 +- 4.9 hours for B lymphocytes in normal subjects, 192.6 hours for T-CLL and 57.7 +- 46.9 hours for B-CLL, and 60.2 +- 30.7 hours for T cell type of malignant lymphoma (T-ML) and 63.7 +- 24.5 hours for B cell type of malignant lymphoma (B-ML). These data might suggest that all lymphocyte disappearance curve reflected T lymphocyte disappearance curve chiefly, and the half time of B lymphocytes was shorter than that of T lymphocytes. In the T-CLL, the half time of the second component prolonged extremely in comparison with that of normal T lymphocytes. The labeled cells were accumulated in the lungs, spleen and liver immediately after the infusion, then in the spleen most remarkably 1 hour after the infusion in all cases. The radioactivity over the bone marrow was observed from 1 hour in all cases and that of lymph nodes were first noticed 18 hours after the infusion in T-CLL and T-ML, 68 hours in B-CLL but were not noticed in normal subjects and B-ML. The recovery of labeled cells in the blood was 28.5 +- 7.9% for all lymphocytes, 19.7 +- 1.9% for T lymphocytes and 11.0 +- 5.1% for B lymphocytes in normal subjects, 25.8 +- 1.6% for CLL, and 17.6 +- 11.0% for T-ML, 7.7 +- 5.2% for B-ML, respectively. (J.P.N.)

Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis

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Rohta Noaki

2009-11-01

Full Text Available A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications.

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

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

2014-04-01

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

Granulomatous colitis: findings on double contrast barium enema and follow-up studies

International Nuclear Information System (INIS)

Song, Jong Gi; Han, Joon Koo; Kim, Seung Hoon; Choo, Sung Wook; Kim, Seung Cheol; Choi, Byung Ihn

1995-01-01

To evaluate the radiologic findings of granulomatous colitis on double contrast barium enema and changes on follow-up studies. Serial double contrast barium enema of six patients with granulomatous colitis confirmed by endoscopic biopsy were reviewed. We analyzed the radiologic findings and their follow-up changes, including aphthous ulcers, lymphoid hyperplasia, deep ulcers, cobble stone appearance, geographic ulcers, asymmetric involvement of ulcers, skip lesions, sinus tract, fistula formation, pseudosacculation, focal stricture, and small bowel involvement. Pretreatment double contrast barium enema findings were aphthous ulcers in five patients, deep ulcer in six, cobble stone appearance in five, longitudinal geographic ulcers in two, fistulas in one, pseudosacculations in two, focal stricture in one, and pseudopolyps in six. Also, anal ulcers were observed in two patients, asymmetric involvement of ulcers in three, skip lesions in four, and small bowel involvement in five in five patients proved to have inactive disease after treatment, aphthous ulcers and deep ulcers disappeared. Geographic ulcers of two patients and anal ulcer of one patients decreased in size or depth. Pseudosacculation in one patient disappeared. Pseudopolyps decreased in two patients, increased in one, and decreased after increase in two. One patient whose disease remained active after treatment showed maintenance or increase of ulcers or fistula. And their pseudosacculation or focal stricture unchanged and pseudopolyps decreased. The major radiologic findings of chronic granulomatous colitis on double contrast barium enema are aphthous ulcer, deep ulcer, cobble stone appearance, discontinuity of the lesion and coexistence of ulcers and pseudopolyps. And, double contrast barium enema is good follow-up modality because its findings correlate with clinical course of the granulomatous colitis after treatment

Fidaxomicin in the treatment of colitis due to Clostridium difficile: preliminary results

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Francesco Cortese

2014-12-01

Full Text Available The incidence of Clostridium difficile infections (CDI and Clostridium difficile-Associated Diarrhea (CDAD is increasing in Canada, USA, and Europe and represents a considerable clinical problem. Both naïve and hypervirulent strains can be considered as opportunistic bacteria affecting immunocompromised, antibiotic-treated, critical, or subcritical patients with a microbiota disruption. CDI arising is strictly related to antibiotic, single or combined, and/or proton pump inhibitor treatment. CDI can cause a syndrome with systemic involvement and complex treatment, sometimes requiring surgical interventions (e.g. colectomy in fulminant colitis. Antibiotic treatment with metronidazole by mouth is the first choice and generally vancomycin is administered in case of lack of effectiveness. Fidaxomicin is a new macrocyclic antibiotic for C. difficile with microflora-sparing properties. This paper reports our initial experience in 11 patients with non-responder or relapsing CDIs. Fidaxomicin was effective in 10 cases (91%. Only one patient with an active ulcerative colitis did not respond and was treated with fecal-microbiota transplantation. In two patients diarrhea persisted, but just the ulcerative colitis one was C. difficile-related. No adverse events were experienced.http://dx.doi.org/10.7175/cmi.v8i1s.956

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

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June-Chul Lee

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

Radiosensitivity of lymphocytes in vitro

International Nuclear Information System (INIS)

Albrecht, S.

1979-01-01

The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60 Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3 H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

GENERATION OF CYTOTOXIC LYMPHOCYTES IN MIXED LYMPHOCYTE REACTIONS

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Forman, James; Möller, Göran

1973-01-01

Generation of cytotoxic effector cells by a unidirectional mixed lymphocyte reaction (MLR) in the mouse H-2 system was studied using labeled YAC (H-2a) leukemia cells as targets. The responding effector cell displayed a specific cytotoxic effect against target cells of the same H-2 genotype as the stimulating cell population. Killing of syngeneic H-2 cells was not observed, even when the labeled target cells were "innocent bystanders" in cultures where specific target cells were reintroduced. Similar results were found with spleen cells taken from mice sensitized in vivo 7 days earlier. The effector cell was not an adherent cell and was not activated by supernatants from MLR. The supernatants were not cytotoxic by themselves. When concanavalin A or phytohemagglutinin was added to the cytotoxic test system, target and effector cells were agglutinated. Under these conditions, killing of H-2a target cells was observed in mixed cultures where H-2a lymphocytes were also the effector cells. These findings indicate that specifically activated, probably thymus-derived lymphocytes, can kill nonspecifically once they have been activated and providing there is close contact between effector and target cells. Thus, specificity of T cell killing appears to be restricted to recognition and subsequent binding to the targets, the actual effector phase being nonspecific. PMID:4269560

The Proteome of Ulcerative Colitis in Colon Biopsies from Adults - Optimized Sample Preparation and Comparison with Healthy Controls.

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Schniers, Armin; Anderssen, Endre; Fenton, Christopher Graham; Goll, Rasmus; Pasing, Yvonne; Paulssen, Ruth Hracky; Florholmen, Jon; Hansen, Terkel

2017-12-01

The purpose of the study was to optimize the sample preparation and to further use an improved sample preparation to identify proteome differences between inflamed ulcerative colitis tissue from untreated adults and healthy controls. To optimize the sample preparation, we studied the effect of adding different detergents to a urea containing lysis buffer for a Lys-C/trypsin tandem digestion. With the optimized method, we prepared clinical samples from six ulcerative colitis patients and six healthy controls and analysed them by LC-MS/MS. We examined the acquired data to identify differences between the states. We improved the protein extraction and protein identification number by utilizing a urea and sodium deoxycholate containing buffer. Comparing ulcerative colitis and healthy tissue, we found 168 of 2366 identified proteins differently abundant. Inflammatory proteins are higher abundant in ulcerative colitis, proteins related to anion-transport and mucus production are lower abundant. A high proportion of S100 proteins is differently abundant, notably with both up-regulated and down-regulated proteins. The optimized sample preparation method will improve future proteomic studies on colon mucosa. The observed protein abundance changes and their enrichment in various groups improve our understanding of ulcerative colitis on protein level. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-Inflammatory Effects of Ethanol Extract of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), in Mice with Ulcerative Colitis.

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Qin, Mingming; Geng, Yan; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Xin; Xu, Zheng-Hong

2016-01-01

This study investigated the anti-inflammatory activity of ethanol extracts of Hericium erinaceus in the inflammatory bowel disease (IBD) model. Twenty C57BL/6 mice were exposed to 2% (w/v) dextran sulfate sodium (DSS) in their drinking water for 7 d to induce acute intestinal inflammation. Orally administrated ethanol extract of H. erinaceus (HEEE) (250 mg/kg/d and 500 mg/kg/d body weight) could significantly (P < 0.05) improve body weight and colon length and decreased the intestinal bleeding of DSS-treated mice compared with DSS-treated mice not given HEEE. HEEE markedly reduced DSS-induced myeloperoxidase accumulation in colon tissues, attenuated histological change in the neutrophils and lymphocyte infiltration, and protected the mucosal epithelium. Mechanistically, HEEE ameliorated colitis not only by suppressing the production of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in colon tissues but also by adjusting the production of nitric oxide, malondialdehyde, and superoxide dismutase in serum to suppress the oxidative stress. These results suggest that HEEE can be applied as a protective agent in the treatment of IBDs.

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

Science.gov (United States)

Ghazzawi, I; Al-Mrayat, Z

2007-01-01

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

Butyrate absorption and lactate secretion in ulcerative colitis

DEFF Research Database (Denmark)

Hove, H; Holtug, K; Jeppesen, P B

1995-01-01

.12. Despite normal butyrate absorption, sodium absorption was compromised in active ulcerative colitis (11.5 +/- 1.4 mumol/cm2/h) compared with quiescent (15.4 +/- 1.0 mumol/cm2/h) and controls (18.7 +/- 0.8 mumol/cm2/h) (P = 0.0006). Mucosal secretion of L-lactate was minimal in both healthy controls...

Mindfulness May Be Helpful for People with Ulcerative Colitis

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... homework. This was compared to a “time/attention” control—a course on mind and body medicine that was similar in format but did not include coping skills, practice, or any information on ulcerative ... the MBSR and control groups in the course of ulcerative colitis disease, ...

Sclerosing cholangitis with ulcerative colitis in a Nigerian woman ...

African Journals Online (AJOL)

Primary Sclerosing Cholangitis (PSC) is a relatively rare cause of chronic liver disease worldwide. It presents as chronic cholestasis associated with jaundice and pruritus. We report a middle aged Nigerian woman who presented with cholestatic jaundice and diagnosed with PSC with concurrent ulcerative colitis based on ...

Association between gastrointestinal motility and macrophage/mast cell distribution in mice during the healing stage after DSS‑induced colitis.

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Kodani, Mio; Fukui, Hirokazu; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

2018-06-01

Irritable bowel syndrome (IBS) frequently occurs after infectious colitis or inflammatory bowel disease in patients with complete remission. This suggests that post‑inflammation‑associated factors may serve a role in the pathophysiology of IBS; however, the mechanism responsible remains unclear. In the present study, the involvement of macrophages and mast cells in alteration of gastrointestinal (GI) motility was investigated in mice in the remission stage after acute colitis. C57BL/6 mice were administered 2% dextran sulfate sodium in drinking water for 5 days and their intestinal tissues were investigated at intervals for up to 24 weeks. Expression of the mannose receptor (MR) and tryptase was examined by immunohistochemistry, and the GI transit time (GITT) was measured by administration of carmine red solution. A minimal degree of inflammatory cell infiltration persisted in the colon and also the small intestine of mice in remission after colitis and the GITT was significantly shorter. The number of muscularis MR‑positive macrophages was significantly increased in the small intestine of mice in remission after colitis and negatively correlated with GITT. Furthermore, results indicated that the number of muscularis tryptase‑positive mast cells was significantly increased throughout the intestine of mice during the healing process after colitis and was positively correlated with GITT. The present findings suggested an increased number of macrophages and/or mast cells in the intestinal muscular layer may be associated with the pathophysiology of GI dysmotility after colitis.

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

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Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

2010-09-07

To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

Identification of internal control genes for quantitative expression analysis by real-time PCR in bovine peripheral lymphocytes.

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Spalenza, Veronica; Girolami, Flavia; Bevilacqua, Claudia; Riondato, Fulvio; Rasero, Roberto; Nebbia, Carlo; Sacchi, Paola; Martin, Patrice

2011-09-01

Gene expression studies in blood cells, particularly lymphocytes, are useful for monitoring potential exposure to toxicants or environmental pollutants in humans and livestock species. Quantitative PCR is the method of choice for obtaining accurate quantification of mRNA transcripts although variations in the amount of starting material, enzymatic efficiency, and the presence of inhibitors can lead to evaluation errors. As a result, normalization of data is of crucial importance. The most common approach is the use of endogenous reference genes as an internal control, whose expression should ideally not vary among individuals and under different experimental conditions. The accurate selection of reference genes is therefore an important step in interpreting quantitative PCR studies. Since no systematic investigation in bovine lymphocytes has been performed, the aim of the present study was to assess the expression stability of seven candidate reference genes in circulating lymphocytes collected from 15 dairy cows. Following the characterization by flow cytometric analysis of the cell populations obtained from blood through a density gradient procedure, three popular softwares were used to evaluate the gene expression data. The results showed that two genes are sufficient for normalization of quantitative PCR studies in cattle lymphocytes and that YWAHZ, S24 and PPIA are the most stable genes. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

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

2009-10-01

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

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.

Science.gov (United States)

Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

2016-01-09

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.

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Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Kuśnierz-Cabala, Beata; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Gil, Krzysztof; Olszanecki, Rafał; Pihut, Małgorzata; Dembiński, Artur

2017-05-24

Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

G protein-coupled receptor kinase-2-deficient mice are protected from dextran sodium sulfate-induced acute colitis.

Science.gov (United States)

Steury, Michael D; Kang, Ho Jun; Lee, Taehyung; Lucas, Peter C; McCabe, Laura R; Parameswaran, Narayanan

2018-06-01

G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays a key role in different disease processes. Previously, we showed that GRK2 knockdown enhances wound healing in colonic epithelial cells. Therefore, we hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate (DSS)-induced acute colitis. To test this, we administered DSS to wild-type (GRK2 +/+ ) and GRK2 heterozygous (GRK +/- ) mice in their drinking water for 7 days. As predicted, GRK2 +/- mice were protected from colitis as demonstrated by decreased weight loss (20% loss in GRK2 +/+ vs. 11% loss in GRK2 +/- ). lower disease activity index (GRK2 +/+ 9.1 vs GRK2 +/- 4.1), and increased colon lengths (GRK2 +/+ 4.7 cm vs GRK2 +/- 5.3 cm). To examine the mechanisms by which GRK2 +/- mice are protected from colitis, we investigated expression of inflammatory genes in the colon as well as immune cell profiles in colonic lamina propria, mesenteric lymph node, and in bone marrow. Our results did not reveal differences in immune cell profiles between the two genotypes. However, expression of inflammatory genes was significantly decreased in DSS-treated GRK2 +/- mice compared with GRK2 +/+ . To understand the mechanisms, we generated myeloid-specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was sufficient for the protection from DSS-induced colitis. Together our results indicate that deficiency of GRK2 protects mice from DSS-induced colitis and further suggests that the mechanism of this effect is likely via GRK2 regulation of inflammatory genes in the myeloid cells.

Treatment tactics in patient with rectal cancer complicating ulcerative colitis

Directory of Open Access Journals (Sweden)

Yu. A. Barsukov

2012-01-01

Full Text Available A successful treatment of a young patient with a 15-year anamnesis of ulcerative colitis, who has been diagnosed with rectal cancer, is presented in this case report. A non-standard surgical intervention has been performed following all principles of oncologic surgery. A subtotal colectomy has been performed with ultra-low anterior resection of rectum. Ascendoanal anastomosis has been performed forming the neo-rectum. There were no complications in postoperative period. Considering disease stage (T3N1M0 adjuvant XELOX was administered for 6 months along with 2 cycles of prophylactic treatment with 5-aminosalycilic acid. During 2-years follow-up there are no signs of rectal cancer and ulcerative colitis progression. After pelvic electrostimulation defecation frequency decreased to 3–4 times per day, a patient has complete social rehabilitation.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis

DEFF Research Database (Denmark)

Mark-Christensen, A; Erichsen, R; Brandsborg, S

2018-01-01

BACKGROUND: The ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain risk factors associated with failure. METHOD: 1,991 patients with ulc......BACKGROUND: The ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain risk factors associated with failure. METHOD: 1,991 patients......-anal anastomosis from Denmark, where pouch surgery is centralized, females had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure. This article is protected by copyright. All rights reserved....

Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

Science.gov (United States)

Mizukami, Tomoyuki; Obara, Megumi; Nishikomori, Ryuta; Kawai, Tomoki; Tahara, Yoshihiro; Sameshima, Naoki; Marutsuka, Kousuke; Nakase, Hiroshi; Kimura, Nobuhiro; Heike, Toshio; Nunoi, Hiroyuki

2012-02-01

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

International Nuclear Information System (INIS)

Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A.; Porzner, M.; Seufferlein, T.; Metz, H.; Maeder, K.; Christ, B.

2015-01-01

The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice

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Walldorf, J.; Hermann, M.; Pohl, S.; Zipprich, A. [Martin Luther University Halle-Wittenberg, Department of Internal Medicine I, Halle (Germany); Porzner, M.; Seufferlein, T. [University of Ulm, Department of Internal Medicine I, Ulm (Germany); Metz, H.; Maeder, K. [Martin Luther University, Institut of Pharmacy, Halle-Wittenberg (Germany); Christ, B. [University of Leipzig, Department of Surgery II, Leipzig (Germany)

2015-10-15

The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. (orig.)

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

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Ana Cardoso

2018-03-01

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

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

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Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

2009-01-01

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

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

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

2005-10-31

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

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

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Ando Tomoaki

2005-10-01

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

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

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

2013-01-01

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

Chemokines, lymphocytes, and HIV

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Farber J.M.

1998-01-01

Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

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Jeroen Pouwels

2013-11-01

Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

Optimal management of steroid-dependent ulcerative colitis

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Khan HMW

2015-11-01

Full Text Available Hafiz M Waqas Khan,1 Faisal Mehmood,1 Nabeel Khan2 1Department of Medicine, King Edward Medical University, Lahore, Pakistan; 2Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA Abstract: Ulcerative colitis (UC is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date. Keywords: ulcerative colitis, steroid dependent, thiopurines, MTX, adalimumab, infliximab

Golimumab for the treatment of ulcerative colitis

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Löwenberg M

2014-03-01

Full Text Available Mark Löwenberg,1 Nanne KH de Boer,2 Frank Hoentjen3 1Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands; 2Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, the Netherlands; 3Inflammatory Bowel Disease Center, Radboud University Medical Center, Nijmegen, the Netherlands Abstract: The introduction of therapeutic antibodies against tumor necrosis factor (TNF had a major impact on the treatment of ulcerative colitis (UC. Infliximab and adalimumab are powerful agents that are used for remission induction and maintenance therapy in UC and have an acceptable safety profile. However, a proportion of UC patients for whom therapy with anti-TNF agents is indicated fail or become intolerant to treatment with infliximab or adalimumab. Hence, there remains an unmet need for novel anti-TNF agents. Golimumab (Simponi®, a human anti-TNF antibody that is administered by monthly subcutaneous injections, is the most recently introduced TNF blocker for the treatment of UC. Here, we will discuss recent literature on clinical efficacy and safety of golimumab induction and maintenance treatment in patients with UC. Furthermore, we will discuss the positioning of golimumab for UC in current treatment algorithms. Keywords: ulcerative colitis, UC, antitumor necrosis factor, TNF, antibodies, golimumab

Laboratorial diagnosis of lymphocytic meningitis

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Sérgio Monteiro de Almeida

Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.

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Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine; Laukens, Debby

2017-04-01

The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila , bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD. IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we

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

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Marco Constante

2017-09-01

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

Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS in Mice Treated with FR91

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Valter R. M. Lombardi

2012-01-01

Full Text Available One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC. However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS. Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

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

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Grigorios Voulalas

2016-01-01

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

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

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

2013-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

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Montoro, Miguel A; Brandt, Lawrence J; Santolaria, Santos; Gomollon, Fernando; Sánchez Puértolas, Belén; Vera, Jesús; Bujanda, Luis; Cosme, Angel; Cabriada, José Luis; Durán, Margarita; Mata, Laura; Santamaría, Ana; Ceña, Gloria; Blas, Jose Manuel; Ponce, Julio; Ponce, Marta; Rodrigo, Luis; Ortiz, Jacobo; Muñoz, Carmen; Arozena, Gloria; Ginard, Daniel; López-Serrano, Antonio; Castro, Manuel; Sans, Miquel; Campo, Rafael; Casalots, Alex; Orive, Víctor; Loizate, Alberto; Titó, Lluçia; Portabella, Eva; Otazua, Pedro; Calvo, M; Botella, Maria Teresa; Thomson, Concepción; Mundi, Jose Luis; Quintero, Enrique; Nicolás, David; Borda, Fernando; Martinez, Benito; Gisbert, Javier P; Chaparro, María; Jimenez Bernadó, Alfredo; Gómez-Camacho, Federico; Cerezo, Antonio; Casal Nuñez, Enrique

2011-02-01

There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Prebiotics and synbiotics in ulcerative colitis.

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Laurell, Axel; Sjöberg, Klas

2017-04-01

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

Effect of radiotherapy on lymphocyte cytotoxicity in vitro

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Wasserman, J; Melen, B [Central Microbiological Laboratory, Stockholm County Council (Sweden); Blomgren, H; Glas, U; Perlmann, P

1975-11-01

The cytotoxic functions of highly purified blood lymphocytes from patients with breast cancer were studied before and after radiotherapy. Addition of PHA or of rabbit antibodies to target cells (chicken erythrocytes) were chosen as two means of inducing lymphocyte cytotoxicity in vitro. The proportion of T and non-T lymphocytes was determined by means of E and EAC rosette tests. The antibody-induced cytotoxicity of lymphocytes decreased following radiotherapy while that mediated by PHA remained unchanged. There was some reduction in the percentage of EAC rosette-forming cells. These results, as well as earlier observations, suggest that the decrease in the peripheral blood of the proportion of lymphocytes with receptors for activated complement is responsible for changes in the antibody-mediated lymphocyte cytotoxicity.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

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Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

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

Directory of Open Access Journals (Sweden)

Yozo Suzuki

2010-05-01

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

Measurement of exercise-induced oxidative stress in lymphocytes.

Science.gov (United States)

Turner, James E; Bosch, Jos A; Aldred, Sarah

2011-10-01

Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

Faecal Bacterial Communities in Healthy Controls and Ulcerative Colitis Patients

DEFF Research Database (Denmark)

Vigsnæs, Louise Kristine; Wilcks, Andrea; Brynskov, Jørn

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) that is characterized by chronic inflammation of the colonic mucosa. The aetiology of IBD is not well understood, however the commensal intestinal microbiota is thought to play an important pathogenetic role. Hence...

Protective effects of two Astragalus species on ulcerative colitis in rats

African Journals Online (AJOL)

management of UC are corticosteroids, 5- ... toothache, and neck pain, or orally for treating .... Macroscopic assessment of ulcerative colitis ... (version 8) software package (SPSS Inc, USA). ..... University Press, Edinburgh, 1970: 49–254. 6.

Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice

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Jahidul Islam

2017-07-01

Full Text Available Rice bran (RB is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group by dextran sodium sulfate (DSS. Body weight change, disease activity index (DAI, histopathology score, tissue myeloperoxidase (MPO activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript (Tnf-α, Il-1β, Il-6, and Il-17 levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis.

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

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

2015-11-15

In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. Copyright © 2015 by The American Association of Immunologists, Inc.

Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice.

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Okada, Toshihiko; Otsubo, Takeshi; Hagiwara, Teruki; Inazuka, Fumika; Kobayashi, Eiko; Fukuda, Shinji; Inoue, Takuya; Higuchi, Kazuhide; Kawamura, Yuki I; Dohi, Taeko

2017-09-01

Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro . Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum . Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro . In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

Advanced colonic cancer associated with radiation colitis, report of a case

Energy Technology Data Exchange (ETDEWEB)

Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Matsumoto, Takayuki [Kyushu Univ., Fukuoka (Japan). Hospital

2002-07-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Advanced colonic cancer associated with radiation colitis, report of a case

International Nuclear Information System (INIS)

Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo; Matsumoto, Takayuki

2002-01-01

A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis

DEFF Research Database (Denmark)

Hillingsø, J.G.; Kjeldsen, J.; Schmidt, P.T.

2002-01-01

reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis.Methods: In a randomized, double-blind, placebo-con trolled study, concentrations of leukotriene B-4...... rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon.Results: No significant...... changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon.Conclusions: These findings...

Small-bowel permeability in collagenous colitis

DEFF Research Database (Denmark)

Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

2006-01-01

Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies......, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability....

Metal ion levels and lymphocyte counts

DEFF Research Database (Denmark)

Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole

2013-01-01

BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA) an....../ppb. INTERPRETATION: Circulating T-lymphocyte levels may decline after surgery, regardless of implant type. Metal ions-particularly cobalt-may have a general depressive effect on T- and B-lymphocyte levels. Registered with ClinicalTrials.gov under # NCT01113762.......BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA....... RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...

Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

Energy Technology Data Exchange (ETDEWEB)

Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

2008-11-15

We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

[Clinical extraintestinal manifestations in patients with ulcerative colitis].

Science.gov (United States)

Toader, Elena

2007-01-01

Ulcerative colitis (UC) is a chronic disease clinically manifest either by bowel symptoms alone or extraintestinal symptoms. Our prospective study included 635 patients with ulcerative colitis (334 males and 301 females, mean age 37.54 +/- 13.84, range 20-70 years). The presence of the common extraintestinal symptoms (ES) was analyzed. Of the 635 investigated patients, these symptoms were found in 83 (13%, 49 males and 34 females, mean age 41.6 +/- 13.95 range 21-70). Patients with ES suffered longer from UC on the average, that is 60.6 years. Most commonly ES involved the joints, 38 (45.8%) patients, hepatobiliary, 28 patients (33.7%), skin, 10 patients (12%) and eyes, 7 patients (8.4%). In 18% of the patients two or more ES were present. ES were clinically detectable after the intestinal symptoms in 81% patients. An increased tendency of ES to occur in patients with a more extensive disease was noticed. The prevalence of ES in the UC patients from NE Romania is in agreement with data from other countries. The number of ES supports the need for complex follow-up in these patients.

Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

DEFF Research Database (Denmark)

Perner, Anders; Lassen, Inge Nordgaard; Matzen, Peter

2002-01-01

BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients...... by neutron activation analysis and the chemiluminescence technique, respectively. RESULTS: The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25...... higher (P gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method...

Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-α antagonists

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Fausel R

2015-01-01

Full Text Available Rebecca Fausel,1 Anita Afzali1,2 1Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA; 2Inflammatory Bowel Disease Program, UW Medicine – Harborview Medical Center, Seattle, WA, USA Abstract: Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. Keywords: ulcerative colitis, inflammatory bowel disease, infliximab, adalimumab, golimumab

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

Science.gov (United States)

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

2015-12-07

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

ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

Directory of Open Access Journals (Sweden)

Giovanni Pallio

2016-08-01

Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

Science.gov (United States)

Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

2008-12-01

The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

A microculture technique for rat lymphocyte transformation.

Science.gov (United States)

Lindsay, V J; Allardyce, R A

1979-01-01

We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

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

Science.gov (United States)

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

1977-12-01

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

Damage of lymphocytes by ionizing irradiation

International Nuclear Information System (INIS)

Rose, H.; Moldenhauer, H.; Kehrberg, G.

1985-01-01

After a short review, how lymphocytes of the peripheral blood are influenced by radiotherapy, the damage of lymphocytes by whole-body irradiation is pointed out in animal experiments and after in vitro irradiation. The special sensibility of B-cells and their homogeneity in fields of radiobiology are opposed to the heterogeneity of T-cells. The radiosensibility of cytotoxic lymphocytes, suppressor cells, and helper cells are discussed. It appears, that within these functional criteria, there is a different radiosensibility, too. (author)

Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

Science.gov (United States)

Alagozlu, Hakan; Gorgul, Ahmet; Bilgihan, Ayse; Tuncer, Candan; Unal, Selahattin

2013-02-01

After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients

Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

DEFF Research Database (Denmark)

Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen

2015-01-01

characterized the molecular phenotype of ulcerative colitis through transcriptomic and metabonomic profiling of colonic mucosal biopsies from patients and controls. We have characterized the extent to which metabonomic and transcriptomic molecular phenotypes are associated with ulcerative colitis versus...... transcriptomic and metabonomic data have previously been shown to predict the clinical course of ulcerative colitis and related clinical phenotypes, indicating that molecular phenotypes reveal molecular changes associated with the disease. Our analyses indicate that variables of both transcriptomics...... and metabonomics are associated with disease case and control status, that a large proportion of transcripts are associated with at least one metabolite in mucosal colonic biopsies, and that multiple pathways are connected to disease-related metabolites and transcripts....

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

Science.gov (United States)

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

2016-01-01

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

Cytomegalovirus colitis after systemic chemotherapy in a patient with recurrent colon cancer: A case report

Directory of Open Access Journals (Sweden)

Teraishi Fuminori

2008-08-01

Full Text Available Abstract Introduction The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. Case presentation We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. Conclusion The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

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

OpenAIRE

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

2005-01-01

Abstract Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammat...

Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

NARCIS (Netherlands)

Kim, Christopher; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Purdue, Mark P; Huang, Wen-Yi; Liu, Chin-San; Cheng, Wen-Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J; Lim, Unhee; Hosgood, H Dean; Bonner, Matthew R; Caporaso, Neil E; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel

BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication

Two cases of rectal cancer accompanied with radiation colitis

International Nuclear Information System (INIS)

Nakazaki, Takayuki; Tobinaga, Koji; Taketomi, Katsuro; Kimino, Koji; Nakasone, Tomonari; Kishikawa, Masao.

1996-01-01

This paper presents two cases of rectal cancer accompanied with radiation colitis. Case 1 was a 53-year-old woman, who had a history of undergoing radiation therapy for a uterine cervical cancer 11 years before. She was seen at the hospital because of constipation and pointed out a IIa-like lesion on the rectum by colonoscopy. Abdominoperineal resection was performed. The surgical specimen showed the IIa-like lesion on the rectum. Pathological findings revealed well-differentiated adenocarcinoma. Immunohistochemical staining of p53 showed positive cells in atrophic glands. Case 2 was a 62-year-old woman complaining of diarrhea. There was a previous history of receiving radiation therapy for a uterine cancer 20 years before. Colonoscopy showed a Borrmann type 2 cancer on the rectum. Abdominoperineal resection was performed. Histological findings revealed moderately differentiated adenocarcinoma invading to the propria muscle. The features of radiation colitis were observed around the cancer in the two cases which provided a clue to diagnose the lesions with radiation-induced cancer. (author)

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

Science.gov (United States)

2012-01-01

Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. Results The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. Summary In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. Conclusion BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice. PMID

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

Science.gov (United States)

Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

2012-10-22

Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.

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Berlec, Aleš; Perše, Martina; Ravnikar, Matjaž; Lunder, Mojca; Erman, Andreja; Cerar, Anton; Štrukelj, Borut

2017-02-01

TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

[The lymphocyte transformation test in dermatology].

Science.gov (United States)

Zinn, K; Braun-Falco, O

1976-03-01

At first, immunologie and methodic basies of the lymphocyte transformation test are discussed. Then the results gained by this test in several dermatologic diseases are summarized. Finally, practice of the lymphocyte transformation test is critically reviewed.

Radiosensitivity of lymphocytes among Filipinos: final report

International Nuclear Information System (INIS)

Medina, F.I.S.; Gregorio, J.S.; Aguilar, C.P.; Poblete, E.E.

1996-01-01

This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis.

Science.gov (United States)

Gong, Xiaohui; Xu, Xiaojuan; Lin, Sisi; Cheng, Yu; Tong, Jianhua; Li, Yongyu

2017-08-01

The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

Science.gov (United States)

Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

2017-08-01

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic review of patient inflammatory bowel disease information resources on the World Wide Web.

Science.gov (United States)

Bernard, André; Langille, Morgan; Hughes, Stephanie; Rose, Caren; Leddin, Desmond; Veldhuyzen van Zanten, Sander

2007-09-01

The Internet is a widely used information resource for patients with inflammatory bowel disease, but there is variation in the quality of Web sites that have patient information regarding Crohn's disease and ulcerative colitis. The purpose of the current study is to systematically evaluate the quality of these Web sites. The top 50 Web sites appearing in Google using the terms "Crohn's disease" or "ulcerative colitis" were included in the study. Web sites were evaluated using a (a) Quality Evaluation Instrument (QEI) that awarded Web sites points (0-107) for specific information on various aspects of inflammatory bowel disease, (b) a five-point Global Quality Score (GQS), (c) two reading grade level scores, and (d) a six-point integrity score. Thirty-four Web sites met the inclusion criteria, 16 Web sites were excluded because they were portals or non-IBD oriented. The median QEI score was 57 with five Web sites scoring higher than 75 points. The median Global Quality Score was 2.0 with five Web sites achieving scores of 4 or 5. The average reading grade level score was 11.2. The median integrity score was 3.0. There is marked variation in the quality of the Web sites containing information on Crohn's disease and ulcerative colitis. Many Web sites suffered from poor quality but there were five high-scoring Web sites.

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

DEFF Research Database (Denmark)

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

2017-01-01

in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular...

Lack of adrenomedullin results in microbiota changes and aggravates azoxymethane and dextran sulfate sodium-induced colitis in mice

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Sonia Martinez-Herrero

2016-11-01

Full Text Available The link between intestinal inflammation, microbiota, and colorectal cancer (CRC is intriguing and the potential underlying mechanisms remain unknown. Here we evaluate the influence of adrenomedullin (AM in microbiota composition and its impact on colitis with an inducible knockout (KO mouse model for AM. Microbiota composition was analyzed in KO and wild type (WT mice by pyrosequencing. Colitis was induced in mice by administration of azoxymethane (AOM followed by dextran sulfate sodium (DSS in the drinking water. Colitis was evaluated using a clinical symptoms index, histopathological analyses, and qRT-PCR. Abrogation of the adm gene in the whole body was confirmed by PCR and qRT-PCR. KO mice exhibit significant changes in colonic microbiota: higher proportion of δ-Proteobacteria class; of Coriobacteriales order; and of other families and genera was observed in KO feces. Meanwhile these mice had a lower proportion of beneficial bacteria, such as Lactobacillus gasseri and Bifidobacterium choerinum. TLR4 gene expression was higher (p<0.05 in KO animals. AM deficient mice treated with DSS exhibited a significantly worse colitis with profound weight loss, severe diarrhea, rectal bleeding, colonic inflammation, edema, infiltration, crypt destruction, and higher levels of pro-inflammatory cytokines. No changes were observed in the expression levels of adhesion molecules. In conclusion, we have shown that lack of AM leads to changes in gut microbiota population and in a worsening of colitis conditions, suggesting that endogenous AM is a protective mediator in this pathology.

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

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Yingxia Zheng

2017-05-01

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

A case of lanthanum carbonate ingestion thought to be phlebosclerotic colitis on CT imaging and abdominal radiograph

International Nuclear Information System (INIS)

Harris, K.; Balcam, S.

2017-01-01

A male admitted in the early hours of the morning, complained of a four week, right sided, non-radiating, dull and intermittent abdominal pain. Imaging suggested a diagnosis of phlebosclerotic colitis which was later discounted when the patients' history of lanthanum carbonate ingestion was examined. Phlebosclerotic colitis mostly affects the Asian population, and its cause is still not known, but can be associated with specific radiographic features. Collections of lanthanum may confuse a diagnosis of phlebosclerotic colitis as well as other factors such as voxel errors, photon starvation and movement. - Highlights: • PC can be non-specific, its cause unknown, diagnosis is often delayed. • PC depends on specific radiographic features. • Lanthanum Carbonate can collect within the lumen and confuses diagnosis. • Voxel errors, photon starvation and patient movement can displace densities.

Management and treatment of distal ulcerative colitis

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Andrea Calafiore

2013-12-01

Full Text Available Ulcerative colitis (UC is a chronic inflammatory condition that is confined to the colonic mucosa. Its main symptoms include diarrhea, rectal bleeding and abdominal pain. Approximately two-thirds of UC patients have disease confined distal to the splenic flexure, which can be treated effectively with topical therapy. This means the active drug can be delivered directly to the site of inflammation, limiting the systemic absorption and potential side effects. Topical treatment with aminosalicylates is the most effective approach in the treatment of these forms, provided that the formulation reaches the upper margin of the disease. Given this, the suppository formulation is the treatment of choice for proctitis and distal sigmoiditis. Thanks to their proximal spread, enemas, foams and gels represent the treatment of choice for proctosigmoiditis and for distal ulcerative colitis. Oral aminosalicylates are less effective than topical therapies in patients with active disease, while the combination of topical and oral treatment is more effective in patients refractory to topical or oral mono-therapy. Topically administered aminosalicylates play an important role in the maintenance of remission, but the long-term adhesion to therapy is poor. For this reason, the oral formulation is the first-line therapy in the maintenance of remission. Refractory patients can be treated with topical steroids or systemic steroids and TNF-alpha inhibitors in severe forms.

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

Science.gov (United States)

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

Science.gov (United States)

Häyry, P.; Defendi, V.

1970-01-01

We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

Induction of colitis in young rats by dextran sulfate sodium.

Science.gov (United States)

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

2005-01-01

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

Diversion procto-colitis: response to treatment with short-chain fatty acids.

Science.gov (United States)

Kiely, E M; Ajayi, N A; Wheeler, R A; Malone, M

2001-10-01

Diversion procto-colitis (DPC) results from a deficiency of luminal short-chain fatty acids (SCFAs). Endoscopic and histopathologic features of the disorder are almost universally present in defunctioned bowel, but symptomatic DPC is less common. Five children with symptomatic DPC underwent endoscopy and rectosigmoid biopsies. An endoscopic index (EI) was used to quantify disease severity. An SCFA mixture was administered into the defunctioned bowel. A good clinical response and improvement in the endoscopic index occurred in all children. Undiversion or rectal excision was carried out in 4 and was curative in each case. One child is awaiting a redo pull through. DPC should be considered in children with a defunctioned colon presenting with evidence of colitis. Histopathology provides supportive evidence and SCFAs may provide effective relief of symptoms. Stoma reversal or rectal excision is curative. Copyright 2001 by W.B. Saunders Company.

A new combination of multiple autoimmune syndrome? Coexistence of vitiligo, autoimmune thyroid disease and ulcerative colitis

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Firdevs Topal

2011-09-01

Full Text Available The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

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

Science.gov (United States)

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

2011-01-01

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

Alteration of lymphocyte functions by 8-methoxypsoralen and longwave ultraviolet radiation. I. Suppressive effects of PUVA on T-lymphocyte migration in vitro

International Nuclear Information System (INIS)

Okamoto, H.; Takigawa, M.; Horio, T.

1985-01-01

We investigated the influence of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet radiation (PUVA) on lymphocyte migration in vitro. Nylon wool-purified, mouse splenic T lymphocytes showed locomotive responses to casein, normal mouse serum (NMS), and zymosan-activated mouse serum (ZAS). Migratory responses to casein and NMS, and to ZAS were remarkably suppressed in lymphocytes exposed to 0.5 J/cm2 UVA plus 0.1 micrograms/ml 8-MOP and to 0.8 J/cm2 UVA plus 8-MOP, respectively. The PUVA treatment used in the present study had no effect on random movement and lymphocyte viability. T lymphocytes cultured in the absence of mitogenic agent for 24 h demonstrated a greater increase in their migration activity than noncultured cells, while lymphocytes cultured after 1.0 J/cm2 PUVA pretreatment remained low. These findings suggest that the therapeutic effect of PUVA on inflammatory skin disorders may be due in part to the suppression of lymphocyte migration

Vascular colitis: a report of two cases

Energy Technology Data Exchange (ETDEWEB)

Park, Chan Il; Han, Chang Yul; Han, Man Chung; Choo, Dong Woon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1973-04-15

The authors report two cases of vascular colitis in Korean with a review of literature. Case I, 20 years old male had severe abdominal pain and bloody diarrhea. Case II was 57 years old male and complained severe abdominal pain. Barium enema colon study on each cases disclosed typical thumbprinting appearance of involved segment. Predisposing factor in case I appeared to be anaphylactoid purpura, and in case II distal obstruction due to adenocarcinoma. The mechanism of vascular was briefly discussed.

B-lymphocytes as key players in chemical-induced asthma.

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Vanessa De Vooght

Full Text Available T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE. We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO mice or severe combined immunodeficiency (SCID mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI (20 µl/ear. On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+ were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl or vehicle (acetone/olive oil (AOO (controls. Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40 and consisted of B effector (Be2- (IL-4 and Be1-lymphocytes (IFN-γ. The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.

Managing Ulcerative Colitis – The Guidelines and Beyond

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Mitchell RKL Lie

2013-11-01

Full Text Available Management guidelines offer clinicians clear, evidence-based and often succinct treatment advice. For ulcerative colitis these guidelines describe the use of 5-ASA, corticosteroids, thiopurines, cyclosporine, and anti-TNFα therapies. However, guidelines do have some drawbacks, mainly a lack of concrete advice concerning patients resistant to these aforementioned therapies. This review gives a short overview of current guidelines and addresses treatment alternatives for conventional therapies.

Reproducible microtechnique for measuring stimulation of human lymphocytes by phytohemagglutinin

International Nuclear Information System (INIS)

Willard, K.E.; Lloyd, E.L.

1977-01-01

Methods based on tritiated thymidine incorporation were used for studies on the blastogenic transformation of human lymphocytes by phytohemagglutinin (PHA) in vitro. A stimulation index was calculated as the ratio of the radioactivity measured in lymphocytes to which PHA had been added to that in similar samples from which PHA was omitted. The stimulation indices have been shown to be reproducible to within 10 percent for the same individuals sampled at different times. The maximum mitotic indices for normal control subjects varied from 249 to 340. Seven to 11 different concentrations of PHA were used with each blood sample tested. The maximum index occurred, for most samples, at concentrations of PHA between 0.0625 μl and 1.0 μl/well. A systematic decrease in the maximum mitotic indices was found with increasing age in the range tested (19 to 58 years). Measurements of the single radium case 03 to 416, aged 70, with a residual body burden of 1.0 μCi 226 Ra gave a maximum value for the mitotic index of 44 at a concentration of 0.25 μl/well. This was a factor of 5 less than the value expected from our normal control subjects

Effect of postirradiation anoxia on radiosensitivity of lymphocytes

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Schrek, R.

1976-01-01

Radiosensitivity was measured by viable-lymphocyte counts and by uridine uptake. The viability of the lymphocytes was based on morphologic characteristics visualized by phase contrast microscopy of the cells in a special slide chamber. Low doses of x rays (10 to 1000 R) and incubation at 37 0 C killed lymphocytes in interphase with the production of pyknotic nuclei (nuclear death), and large doses (6000 R) produced nuclei with clear nucleoplasm (cytoplasmic death). Nuclear, but not cytoplasmic, death was inhibited by incubation of the irradiated cells at 27 0 C. Postirradiation anoxia had no effect on development of the nuclear and cytoplasmic death of lymphocytes irradiated with 100 to 6000 R. Anoxia had no effect on the early response of lymphocytes to phytohemagglutinin (PHA) [increase in ribonucleic acid (RNA) and protein synthesis] but inhibited completely the late effects [increase in deoxyribonucleic acid (DNA) synthesis and transformation into lymphoblastoid cells]. The PHA caused relative radioresistance of lymphocytes under aerobic conditions and, to a lesser extent, under anaerobic conditions. The slight radioresistance induced by PHA in anoxic lymphocytes apparently did not depend on an increase in DNA synthesis or on the transformation to lymphoblastoid cells

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

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Helieh S Oz

2013-06-01

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

Cape Gooseberry [Physalis peruviana L.] Calyces Ameliorate TNBS Acid-induced Colitis in Rats.

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Castro, Jenny; Ocampo, Yanet; Franco, Luis

2015-11-01

Physalis peruviana [cape gooseberry] is highly appreciated for its commercial value. The Colombian ecotype is in great demand in the international market, particularly for the unique morphological characteristics of the calyx, which has extended use as a traditional herbal remedy in Colombia because of its anti-inflammatory properties. In this work, the anti-inflammatory activity of the total ethereal extract of Physalis peruviana calyces was evaluated in preventive and therapeutic protocols in a TNBS acid-induced colitis rat model. Colitis was induced by intrarectal administration of TNBS. An evaluation of macroscopic and histopathological parameters in colonic tissue was performed, along with the determination of myeloperoxidase enzyme activity, cytokine levels and gene expression. Additionally, effects on nitric oxide release by lipopolysaccharide [LPS]-stimulated RAW264.7 macrophages and the scavenging activity of DPPH and ABTS free radicals were determined. The treatment with the Physalis peruviana extract produced a significant improvement in the colonic tissue at both macroscopic and histological levels. IL-1β and TNF-α production was reduced by the extract in both experimental approaches. The groups treated with Physalis peruviana showed a tendency to MUC2 up-regulation and down-regulation of COX-2, iNOS, NLRP3, IL-1β, IL-6 and IL-10 expression. Nitric oxide release in RAW264.7 macrophages was significantly inhibited. The Physalis peruviana extract showed intestinal anti-inflammatory activity in the TNBS-induced colitis model, placing this species' calyx, a natural derivative, as a promising source of metabolites that could be used in treatment for inflammatory bowel disease. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle.

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Xiao, Bo; Yang, Yang; Viennois, Emilie; Zhang, Yuchen; Ayyadurai, Saravanan; Baker, Mark; Laroui, Hamed; Merlin, Didier

2014-03-21

Treatment strategies for inflammatory bowel disease have been constrained by limited therapeutic efficacy and serious adverse effects owing to a lack of receptor for targeted drug delivery to the inflamed colon. Upon inflammation, CD98 expression is highly elevated in colonic epithelial cells and infiltrating immune cells. To investigate whether CD98 can be used as a colitis-targeted delivery receptor, we constructed CD98 Fab'-bearing quantum dots (QDs)-loaded nanoparticles (Fab'-NPs). The resultant Fab'-NPs had desired particle size (~458 nm) with a narrow size distribution and zeta-potential (approximately +19 mV), low cytotoxicity, and excellent fluorescence properties. Electron microscopy images provided direct evidence for the well-dispersed distribution of QDs within spherical Fab'-NPs. Cellular uptake experiments demonstrated that Fab'-NPs were efficiently internalized into Colon-26 and RAW 264.7 cells through the CD98-mediated endocytosis pathway, and showed that the targeting effect of CD98 Fab' markedly increased their cellular uptake efficiency compared with control pegylated QDs-loaded NPs (PEG-NPs). Furthermore, ex vivo studies showed much more effective accumulation of Fab'-NPs in colitis tissue than that of PEG-NPs. These findings suggest that because of inflammation-dependent over-expression of CD98, active colitis-targeted delivery can be accomplished using NPs decorated with CD98 antibody.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

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John E. Mullinax

2018-03-01

Full Text Available PurposeAdoptive cell therapy (ACT using tumor-infiltrating lymphocytes (TIL for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL.Experimental designThirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS, and overall survival (OS.ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92% received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011 TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%, four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months. Grade ≥ 3 immune-related adverse events included hypothyroidism (3, hepatitis (2, uveitis (1, and colitis (1.ConclusionIpilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

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Mullinax, John E; Hall, MacLean; Prabhakaran, Sangeetha; Weber, Jeffrey; Khushalani, Nikhil; Eroglu, Zeynep; Brohl, Andrew S; Markowitz, Joseph; Royster, Erica; Richards, Allison; Stark, Valerie; Zager, Jonathan S; Kelley, Linda; Cox, Cheryl; Sondak, Vernon K; Mulé, James J; Pilon-Thomas, Shari; Sarnaik, Amod A

2018-01-01

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 10 (2.3 × 10 10 to 1.0 × 10 11 ) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis

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Yuusuke Mitsuka

2010-07-01

Full Text Available The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean survival time of 12 months. The initial symptoms are poor and atypical. Because of its rare entity and little knowledge of its treatments, there are few reports of long-term survival. We encountered a very unique case with strong impression on radiological findings of malignant peritoneal methothelioma. We had misdiagnosed it because of the findings and because the time course was similar to that of ischemic colitis. The radiological findings on CT and enema disappeared within one week after antibiotic therapy.

Cooked navy and black bean diets improve biomarkers of colon health and reduce inflammation during colitis.

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Zhang, Claire; Monk, Jennifer M; Lu, Jenifer T; Zarepoor, Leila; Wu, Wendy; Liu, Ronghua; Pauls, K Peter; Wood, Geoffrey A; Robinson, Lindsay; Tsao, Rong; Power, Krista A

2014-05-01

Common beans contain non-digestible fermentable components (SCFA precursors) and phenolic compounds (phenolic acids, flavonoids and anthocyanins) with demonstrated antioxidant and anti-inflammatory potential. The objective of the present study was to assess the in vivo effect of cooked whole-bean flours, with differing phenolic compound levels and profiles, in a mouse model of acute colitis. C57BL/6 mice were fed a 20 % navy bean or black bean flour-containing diet or an isoenergetic basal diet (BD) for 2 weeks before the induction of experimental colitis via 7 d dextran sodium sulphate (DSS, 2 % (w/v) in the drinking-water) exposure. Compared with the BD, both bean diets increased caecal SCFA and faecal phenolic compound concentrations (Pdiets reduced mRNA expression of colonic inflammatory cytokines (IL-6, IL-9, IFN-γ and IL-17A) and increased anti-inflammatory IL-10 (Pdiets enhanced DSS-induced colonic damage as indicated by an increased histological injury score and apoptosis (cleaved caspase-3 and FasL mRNA expression) (Pdiets exerted both beneficial and adverse effects during experimental colitis by reducing inflammatory biomarkers both locally and systemically while aggravating colonic mucosal damage. Further research is required to understand the mechanisms through which beans exert their effects on colonic inflammation and the impact on colitis severity in human subjects.

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

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

2011-01-01

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

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

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Sabrina Cipriani

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

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

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Adrian D Vickers

Full Text Available Biological therapies are increasingly used to treat ulcerative colitis (UC.To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF therapy.A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance.Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI]: 2.19 [1.35-3.55], clinical remission (OR [95% CrI]: 2.81 [1.49-5.49], and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]; there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]. In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0].This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All

The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.

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Ida Casorelli

Full Text Available BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/- mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS. The Mutyh(-/- phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+ regulatory T cells were observed only in Mutyh(-/- mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

Randomised clinical trial: yoga vs written self-care advice for ulcerative colitis.

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Cramer, H; Schäfer, M; Schöls, M; Köcke, J; Elsenbruch, S; Lauche, R; Engler, H; Dobos, G; Langhorst, J

2017-06-01

Perceived stress seems to be a risk factor for exacerbation of ulcerative colitis. Yoga has been shown to reduce perceived stress. To assess the efficacy and safety of yoga for improving quality of life in patients with ulcerative colitis. A total of 77 patients (75% women; 45.5 ± 11.9 years) with ulcerative colitis in clinical remission but impaired quality of life were randomly assigned to yoga (12 supervised weekly sessions of 90 min; n = 39) or written self-care advice (n = 38). Primary outcome was disease-specific quality of life (Inflammatory Bowel Disease Questionnaire). Secondary outcomes included disease activity (Rachmilewitz clinical activity index) and safety. Outcomes were assessed at weeks 12 and 24 by blinded outcome assessors. The yoga group had significantly higher disease-specific quality of life compared to the self-care group after 12 weeks (Δ = 14.6; 95% confidence interval=2.6-26.7; P = 0.018) and after 24 weeks (Δ = 16.4; 95% confidence interval=2.5-30.3; P = 0.022). Twenty-one and 12 patients in the yoga group and in the self-care group, respectively, reached a clinical relevant increase in quality of life at week 12 (P = 0.048); and 27 and 17 patients at week 24 (P = 0.030). Disease activity was lower in the yoga group compared to the self-care group after 24 weeks (Δ = -1.2; 95% confidence interval=-0.1-[-2.3]; P = 0.029). Three and one patient in the yoga group and in the self-care group, respectively, experienced serious adverse events (P = 0.317); and seven and eight patients experienced nonserious adverse events (P = 0.731). Yoga can be considered as a safe and effective ancillary intervention for patients with ulcerative colitis and impaired quality of life. ClinicalTrials.gov identifier: NCT02043600. © 2017 John Wiley & Sons Ltd.

Muscadine Grape (Vitis rotundifolia) or Wine Phytochemicals Reduce Intestinal Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis.

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Li, Ruiqi; Kim, Min-Hyun; Sandhu, Amandeep K; Gao, Chi; Gu, Liwei

2017-02-01

The objective of this study was to determine the anti-inflammatory effects of phytochemical extracts from muscadine grapes or wine on dextran sulfate sodium (DSS)-induced colitis in mice and to investigate cellular mechanisms. Two groups of C57BL/6J mice were gavaged with muscadine grape phytochemicals (MGP) or muscadine wine phytochemicals (MWP), respectively, for 14 days. Acute colitis was induced by 3% DSS in drinking water for 7 days. An additional two groups of mice served as healthy and disease controls. Results indicated that MGP or MWP significantly prevented weight loss, reduced disease activity index, and preserved colonic length compared to the colitis group (p ≤ 0.05). MGP or MWP significantly decreased myeloperoxidase activity as well as the levels of IL-1β, IL-6, and TNF-α in colon (p ≤ 0.05). MGP or MWP caused down-regulation of the NF-κB pathway by inhibiting the phosphorylation and degradation of IκB in a dose-dependent manner. These findings suggest that phytochemicals from muscadine grape or wine mitigate ulcerative colitis via attenuation of pro-inflammatory cytokine production and modulation of the NF-κB pathway.

Dietary n-3 PUFA May Attenuate Experimental Colitis

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Cloé Charpentier

2018-01-01

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

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model.

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de Almeida, Ana Beatriz Albino; Sánchez-Hidalgo, Marina; Martín, Antonio Ramón; Luiz-Ferreira, Anderson; Trigo, José Roberto; Vilegas, Wagner; dos Santos, Lourdes Campaner; Souza-Brito, Alba Regina Monteiro; de la Lastra, Catalina Alarcón

2013-03-07

In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (pArctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of sinomenine on the expression of microRNA-155 in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice.

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Qiao Yu

Full Text Available Sinomenine, a pure alkaloid isolated in Chinese medicine from the root of Sinomenium acutum, has been demonstrated to have anti-inflammatory and immunosuppressive effects. MicroRNAs (miRNAs are gradually being recognized as critical mediators of disease pathogenesis via coordinated regulation of molecular effector pathways.After colitis was induced in mice by instillation of 5% (w/v 2,4,6-trinitrobenzenesulfonic acid (TNBS, sinomenine at a dose of 100 or 200 mg/kg was orally administered once daily for 7 days. We evaluated body weight, survival rate, diarrhea score, histological score and myeloperoxidase (MPO activity. The mRNA and protein expression levels of miR-155, c-Maf, TNF-α and IFN-γ were determined by quantitative RT-PCR and immunohistochemistry, respectively. Sinomenine (100 or 200 mg/kg-treated mice with TNBS-induced colitis were significantly improved in terms of body weight, survival rate, diarrhea score, histological score and MPO activity compared with untreated mice. Both dosages of sinomenine significantly decreased the mRNA and protein expression levels of c-Maf, TNF-α and IFN-γ, which elevated in TNBS-induced colitis. Furthermore, sinomenine at a dose of 200 mg/kg significantly decreased the level of miR-155 expression by 71% (p = 0.025 compared with untreated TNBS-induced colitis in mice.Our study evaluated the effects and potential mechanisms of sinomenine in the anti-inflammatory response via miRNA-155 in mice with TNBS-induced colitis. Our findings suggest that sinomenine has anti-inflammatory effects on TNBS-induced colitis by down-regulating the levels of miR-155 and several related inflammatory cytokines.

The behavior of pig lymphocyte populations in vivo

International Nuclear Information System (INIS)

Binns, R.M.; Licence, S.T.; Pabst, R.

1986-01-01

Lymphocyte migration provides the means of rapidly recognizing and responding to antigen and widely disseminating the resulting immune response. The porcine lymphoid system differs from that of man in structural inversion of lymph nodes and route of lymphocyte recirculation and the existence of two Peyer's patch types, one of which differs from the conventional pattern in structure, cell content and lack of lymphocyte traffic and in its regression in old age. Recirculating T and B lymphocytes enter and leave spleen and lymph nodes by the blood but Null cells do not; lymphocytes also migrate through nonlymphoid tissues. The lung is one such important site, with a small migration in and out of alveolar space and a large traffic associated with the blood vessel wall, predominantly involving T cells. Blood lymphocytes hardly traffic into the peritoneal cavity, yet major traffic of particulate material or cells is possible in this important site of abdominal defense, so often used for immunization, and follows a distinct, well defined route. Cells migrate out of subcutaneous tissue via the draining node. Lymphocytes are produced and emigrate into blood from labelled thymus. They differ in size and surface phenotype from both thymocytes and peripheral T cells. Lymphocytes also migrate from blood into most tissues. In most nonlymphoid tissues, entry relates to blood flow but in many lymphoid tissues it is an active process which differs in tempo and extent, eg, between different nodes and between the two Peyer's patch types

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

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

2018-02-24

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

A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients

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Alejandro Pérez-Pitarch

2015-03-01

Full Text Available Background: Infliximab, an anti-tumour necrosis factor approved for treatment of Crohn's disease and ulcerative colitis, is administered at predefined interdose-intervals. On insufficient response or loss of response, treatment can be intensified. The lack or loss of response is likely related to complex pharmacokinetics of infliximab. Aims: To explore optimal dosing strategies of infliximab in treatment-naïve patients with ulcerative colitis through predictive Monte Carlo simulations based on a validated population PK model. Methods: A population of 2,000 treatment-naïve patients was generated by Montecarlo simulation. Six dosing strategies for maintenance therapy were simulated on this population. Strategies 1 and 2 consisted on 5 mg/kg and 6 mg/kg doses, respectively, and 8 weeks inter-dose interval. Strategies 3 and 4 used Individualized doses, adjusted to albumin level, sex and body weight, and a fix inter-dose interval of 8 weeks to achieve a target trough concentration of 5 mg/L or 6 mg/L, respectively. Strategies 5 and 6 used a fix dose of 5 mg/kg and individualized inter-dose intervals, adjusted to the same covariates, to achieve a target concentration, of 5 mg/L or 6 mg/L, respectively. Results: Strategies 2-6 reached trough levels statistically higher than strategy 1 (p < 0.05. Strategy 5 proved to be the best dosing strategy. It was associated with a higher proportion of responder patients than strategy 1 (62 % vs. 40 % without reaching higher peak concentrations. Conclusions: Optimization of maintenance treatment of colitis with infliximab by a pharmacokinetic approach could benefit infliximab-naive patients with ulcerative colitis.

Pterostilbene 4′-β-Glucoside Protects against DSS-Induced Colitis via Induction of Tristetraprolin

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Yingqing Chen

2017-01-01

Full Text Available Pterostilbene, a dimethyl ester analog of resveratrol, has anti-inflammatory and antioxidative effects and alters cell proliferation. Tristetraprolin (TTP promotes the degradation of proinflammatory mediators via binding to adenosine and uridine- (AU- rich elements (ARE located in the 3′-untranslated regions of mRNAs. Here, we utilized pterostilbene 4′-β-glucoside (4-PG, a compound derived from pterostilbene, to investigate whether it has anti-inflammatory effects on dextran sulfate sodium- (DSS- induced colitis via TTP enhancement. TTP expression was increased in 4-PG dose- and time-dependent manners in RAW264.7 cells. The production of proinflammatory cytokine, such as TNF-α, was reduced by 4-PG in vitro. To investigate the role of TTP in the anti-inflammatory effects of 4-PG, we used DSS-induced colitis in TTP WT and KO mice as models. The expression levels of TTP and proinflammatory cytokines were determined in serum and colon tissue. 4-PG increased the expression of TTP while suppressing proinflammatory cytokines both in vitro and in vivo. These findings suggest that treatment with 4-PG mediates the anti-inflammatory effects of 4-PG on DSS-induced colitis via enhancing TTP expression.

Refractory ulcerative colitis complicated by cytomegalovirus infection successfully treated with valganciclovir

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Tiziana Larussa

2012-11-01

Full Text Available Cytomegalovirus (CMV infection is widespread in the general population. In patients with severe and/or steroid-refractory ulcerative colitis (UC, local reactivation of CMV can be detected in actively inflamed colonic tissue in approximately 30% of cases. However, the role of CMV in patients with UC is not clearly understood. There is evidence to show a possible role in exacerbating a colitis flare, whereas other studies describe CMV as an innocent bystander. We report the case of a patient with severe UC complicated by CMV infection who did not respond to conventional therapy. A complete diagnostic panel for CMV diagnosis, including tissue polymerase chain reaction and immunohistochemistry, was carried out. Three-week therapy with oral valganciclovir resulted in dramatic clinical and endoscopic improvement. Timing of diagnosis and treatment of CMV infection complicating UC is crucial in order to recognize the organ-disease and plan appropriate treatment.

Immune-related Colitis Induced by the Long-term Use of Nivolumab in a Patient with Non-small Cell Lung Cancer.

Science.gov (United States)

Yasuda, Yuichiro; Urata, Yoshiko; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Hattori, Yoshihiro; Tsuda, Masahiro; Sakuma, Toshiko; Negoro, Shunichi; Satouchi, Miyako

2018-05-01

We herein report a case of immune-related colitis induced by the long-term use of nivolumab. A 62-year-old Japanese man was treated with nivolumab at 3 mg/kg every 2 weeks for advanced lung adenocarcinoma. The patient was admitted to our hospital due to non-bloody watery diarrhea after the 70th dose of nivolumab. A biopsy specimen of the colon mucosa revealed evidence of colitis with cryptitis and crypt microabscesses. He was diagnosed with immune-related colitis and started on predonisolone 60 mg/day. Subsequently, his symptoms remarkably resolved. Consideration of immune-related adverse events up to several years after the initiation of nivolumab is important.

2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio

NARCIS (Netherlands)

Lin, Bochao Danae; Carnero-Montoro, Elena; Bell, Jordana T; Boomsma, Dorret I; de Geus, Eco J; Jansen, Rick; Kluft, Cornelis; Mangino, Massimo; Penninx, Brenda; Spector, Tim D; Willemsen, Gonneke; Hottenga, Jouke-Jan

2017-01-01

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and

Differentiation of B and T lymphocytes from precursor cells resident in the bone marrow

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Rosse, C; Press, O W

1978-01-01

A series of experiments in guinea pigs and mice established that proliferating progenitor cells for B and T lymphocytes are a resident population in the bone marrow. It was shown by the combined use of /sup 3/H-TdR radioautography and fluorescent-antibody staining of B and T cells that the majority of bone marrow (BM) lymphocytes are rapidly renewed (RR) B cells and null cells, whereas the thymus (THY) consists overwhelming of RR T lymphocytes; in spleen (SPL) and lymph node (LN) slowly renewed (SR) T and B cells predominate. The rate of B cell turnover in guinea pig bone marrow exceeds that in the SPL or LN, and the appearance of newly generated B cells in the SPL lags behind that in the BM. When systematically administered /sup 3/H-TdR was excluded by tourniquets from tibial and femoral BM no labeled B cells appeared in tibial or femoral marrow over 72 h. When tibial and femoral BM was labeled selectively with /sup 3/H-TdR, labeled B cells appeared in the SPL and LN over 72 h. (It was found in CBA mice that BM cell fractions enriched in lymphocytes (BML) responded to the T cell mitogen PHA in a manner qualitatively different from the response of SPL and LN cells. Experiments with athymic nude mice and with complement-mediated lysis of T and B cells established that PHA responsive cells in SPL and LN were T cells but in BML they were null lymphocytes. Target cells of PHA in BML responded to the mitogen by the generation of T-cell surface markers and blastogenesis; therefore they were identified as pre-T cells. BM pre-T cells are rapidly renewed and, in contrast to PHA responsive cells of SPL and LN, do not recirculate from blood to lymph. Both B and pre-T cells in the BM are division products of transitional cells. Among transitional cells of the marrow are included the progenitors of B and T lmyphhocytes and of all other types of hemopoietic cells.

Preventive Effect of TU-100 on a Type-2 Model of Colitis in Mice: Possible Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells

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Atsushi Kaneko

2013-01-01

Full Text Available Purpose. Crohn's disease (CD and ulcerative colitis (UC, the two major forms of inflammatory bowel disease (IBD, have histopathologically and immunologically different characteristics. We previously reported that a traditional Japanese medicine, daikenchuto (TU-100, ameliorated a trinitrobenzenesulfonic acid- (TNBS- induced type-1 model colitis exhibiting histopathological features of CD through adrenomedullin (ADM enhancement. Our current aims were to examine whether TU-100 ameliorates a type-2 model colitis that histologically resembles UC and identify the active ingredients. Methods. TU-100 was administered orally to mice with oxazolone- (OXN- induced type-2 model colitis. The morbidity was evaluated by body weight loss and the macroscopic score of colonic lesions. ADM was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon ulceration. ADM production by intestinal epithelial cells was increased by TU-100 addition. Screening to identify active ingredients showed that [6]-shogaol and hydroxy α-sanshool enhanced ADM production. Conclusions. TU-100 exerted a protective effect in OXN-induced type-2 model colitis, indicating that TU-100 may be a beneficial agent for treatment of UC.

Separation and properties of EA-rosette-forming lymphocytes in humans

NARCIS (Netherlands)

van Oers, M. H.; Zeijlemaker, W. P.; Schellekens, P. T.

1977-01-01

Human peripheral blood lymphocytes were separated into subpopulations enriched or depleted with respect to B lymphocytes (Ig-bearing cells), T lymphocytes, (cell forming rosettes with sheep erythrocytes: E-RFC) and Fc receptor-bearing lymphocytes (EA-RFC). From the distributions and recoveries of