IBD on PubMed

How to Prevent Depression? Current Directions and Future Challenges in Children with Chronic Medical Conditions.

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How to Prevent Depression? Current Directions and Future Challenges in Children with Chronic Medical Conditions.

Psychiatr Danub. 2016 Dec;28(4):441-451

Authors: Felnhofer A, Kothgassner OD, Klier C

Abstract
With its high rates of chronicity and concomitant economic costs to society, depression ranges among the most prevalent mental disorders. Several trials have succeeded in demonstrating the beneficial effects of early depression prevention programs for otherwise healthy children and adolescents. However, comparable programs for children and adolescents with a medical condition are still scarce. This paper discusses the situation of chronically ill children and adolescents who are at risk of developing comorbid depressive symptoms using the example of three conditions frequently encountered in pediatric psychosomatic medicine: diabetes, epilepsy and inflammatory bowel disease (IBD). Each patient group is introduced with regards to specific risk factors and correlates of depression. Also, existing customized depression prevention programs and according research trials are presented. Reviewing the body of literature, it becomes apparent that risk factor research and depression prevention are still in their infancy for these three patient groups. While new risk factor models and biomarker approaches emerge as a promising rationale for depression prevention, research is called upon to include randomized control trials as well as longitudinal designs in order to achieve more optimally tailored preventive interventions for children and adolescents with chronic medical conditions.

PMID: 27855438 [PubMed - in process]

Impact of Treatment-Related Beliefs on Medication Adherence in Immune-Mediated Inflammatory Diseases: Results of the Global ALIGN Study.

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Impact of Treatment-Related Beliefs on Medication Adherence in Immune-Mediated Inflammatory Diseases: Results of the Global ALIGN Study.

Adv Ther. 2016 Nov 16;

Authors: Michetti P, Weinman J, Mrowietz U, Smolen J, Peyrin-Biroulet L, Louis E, Schremmer D, Tundia N, Nurwakagari P, Selenko-Gebauer N

Abstract
INTRODUCTION: Medication adherence is critical in chronic immune-mediated inflammatory diseases (IMIDs) and could be affected by patients' treatment-related beliefs. The objective of this study was to determine beliefs about systemic medications in patients with IMIDs and to explore the association of those beliefs and other factors with adherence.
METHODS: This was a multi-country, cross-sectional, self-administered survey study. Included were adults diagnosed with one of six IMIDs receiving conventional systemic medications and/or tumor necrosis factor inhibitors (TNFi). Patients' necessity beliefs/concerns towards and adherence to treatments were assessed by the Beliefs about Medicines Questionnaire and four-item Morisky Medication Adherence Scale. Correlation of patients' beliefs about treatment and other factors with adherence were evaluated by multivariable regression analyses.
RESULTS: Among studied patients (N = 7197), 32.0% received TNFi monotherapy, 27.7% received TNFi-conventional combination therapy, and 40.3% received conventional medications. Across IMIDs, high adherence to systemic treatment was more prevalent in TNFi groups (61.3-80.7%) versus corresponding conventional treatment groups (28.4-64.7%). In at least four IMIDs, greater perception of the illness continuing forever (P < 0.001), of the treatment helping (P < 0.001), and more concerns about the illness (P < 0.01), but not clinical parameters, were associated with higher treatment necessity beliefs. Higher treatment necessity beliefs, older age, Caucasian race, and TNFi therapy were associated with high medication adherence in at least four IMIDs.
CONCLUSIONS: Treatment necessity beliefs were higher than concerns about current medication in patients with IMID. Illness perceptions had a greater impact on treatment necessity beliefs than clinical parameters. Older age, greater treatment necessity beliefs, and TNFi therapy were associated with high self-reported medication adherence in at least four IMIDs.
TRIAL REGISTRATION: ACTRN12612000977875.
FUNDING: AbbVie.

PMID: 27854054 [PubMed - as supplied by publisher]

Rate and Predictors of Mucosal Healing in Ulcerative Colitis Treated with Thiopurines: Results of a Multicentric Cohort Study.

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Rate and Predictors of Mucosal Healing in Ulcerative Colitis Treated with Thiopurines: Results of a Multicentric Cohort Study.

Dig Dis Sci. 2016 Nov 16;

Authors: Prieux-Klotz C, Nahon S, Amiot A, Sinayoko L, Galéano-Cassaz C, Chaussade S, Coriat R, Lahmek P, Abitbol V

Abstract
BACKGROUND AND AIMS: Mucosal healing (MH) with thiopurines has been poorly investigated in ulcerative colitis (UC). We aimed to assess MH rate in UC patients treated with thiopurine monotherapy.
PATIENTS AND METHODS: We retrospectively collected all UC patients treated with thiopurines more than 6 months who have undergone colonoscopy at baseline and after at least 6 months of treatment. Patients were recruited from January 2005 to May 2015 through a personal database and/or standardized hospital inpatient diagnostic dataset. Patients were excluded in case of any use of other immunomodulator or biological agent. MH was defined as a Mayo endoscopic subscore ≤1 and UCEIS ≤ 2. Histological healing (HH) was defined by the absence of epithelial polynuclear infiltrate, cryptic abscesses, or ulcerations.
RESULTS: Eighty patients (31 women, median age 43 [IQR 32-58]) were included. Median disease duration was 10.5 [6-16] years. At baseline, median full Mayo score, endoscopic subscore, and UCEIS were 8 [6.8-10], 3 [2-3], and 5 [3-6], respectively. MH was first assessed after a mean follow-up of 38 ± 31 months. Median full Mayo score, endoscopic subscore, and UCEIS decreased to 3.5 [1-6], 2 [0-2.2], and 2 [0-4], respectively. MH was achieved in 43.7%, HH in 38%. In multivariate analysis, predictors of MH were thiopurine exposure duration ≥2 years [odds ratio (OR) 2.9, CI 95% (1.1-7.6), p = 0.03] and a prior acute severe colitis [OR 5.9, CI 95% (1.1-32), p = 0.04]. Factors associated with MH during treatment were partial Mayo score ≤2 (NPV = 100%), BMI ≥ 25 kg/m(2) (NPV = 75%), and MCV ≥ 95 fL (NPV = 73%).
CONCLUSIONS: In UC, thiopurine monotherapy is associated with MH in 43.7% and HH in 38%.

PMID: 27853898 [PubMed - as supplied by publisher]

Altered expression of IL36γ and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung's disease.

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Altered expression of IL36γ and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung's disease.

Pediatr Surg Int. 2016 Nov 16;

Authors: Tomuschat C, O'Donnell AM, Coyle D, Puri P

Abstract
PURPOSE: Hirschsprung's disease associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function and abnormal microbiota are implicated in the pathogenesis of HAEC. IL-36γ, a member of the IL-1 superfamily, is involved in host defense and contributes to proinflammatory responses and development of inflammatory diseases. The IL36 receptor (IL1RL2) is an important mediator molecule in the inflammatory response. Animal data suggests that IL1RL2 is involved in mucosal healing. We designed this study to investigate the hypothesis that the IL-36γ axis is altered in HSCR.
METHODS: We investigated IL-36γ and IL1RL2 expression in ganglionic and aganglionic bowel of HSCR patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed.
MAIN RESULTS: qPCR and Western blot analysis revealed that IL-36γ is strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. ILR1L2 expression was significantly decreased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of IL36γ in the colonic epithelium of patients with HSCR compared to controls. IL1RL2 was localized in the colonic epithelium and showed a markedly decreased expression in all HSCR specimens.
CONCLUSION: To our knowledge, we report for the first time the expression of IL36γ and ILRL2 in the colon of patients with HSCR. The increased expression of IL36γ and the markedly decreased expression of IL1RL2 in the aganglionic and ganglionic bowel in HSCR may result in an increased inflammatory response and altered mucosal response healing leading to the susceptibility to develop HAEC.

PMID: 27853811 [PubMed - as supplied by publisher]

Clinical usefulness of narrow band imaging magnifying colonoscopy for assessing ulcerative colitis-associated cancer/dysplasia.

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Clinical usefulness of narrow band imaging magnifying colonoscopy for assessing ulcerative colitis-associated cancer/dysplasia.

Endosc Int Open. 2016 Nov;4(11):E1183-E1187

Authors: Nishiyama S, Oka S, Tanaka S, Sagami S, Hayashi R, Ueno Y, Arihiro K, Chayama K

Abstract
Background and study aims: Colitis-associated cancer/dysplasia (CC/D) can affect the life expectancy of patients with ulcerative colitis (UC). Although the utility of magnifying chromocolonoscopy has been shown, the use of optical magnification with narrow band imaging (NBI) for distinguishing CC/D from non-neoplastic lesions in patients with UC has not been reported. We evaluated whether endoscopic findings are distinguishing and thus assessed the clinical usefulness of NBI magnification for differentiating UC-associated lesions. Patients and methods: The study involved 27 patients diagnosed and treated at Hiroshima University Hospital between September 2005 and March 2015: a neoplasia group (16 lesions) and a non-neoplasia group (17 lesions). The neoplasias comprised 9 dysplastic lesions, 5 intramucosal carcinomas, and 2 submucosal carcinomas, and 17 non-neoplastic lesions. Targeted biopsy samples of suspicious lesions detected by conventional colonoscopy were classified pathologically as neoplastic or non-neoplastic, and NBI magnifying colonoscopy findings (i. e., the surface [unclear/regular/irregular/amorphous] and vascular [same as the background mucosa/regular/irregular/avascular] patterns) of the 2 lesion types were compared. Results: Irregular/amorphous surface patterns were significantly more common in neoplastic lesions than in non-neoplastic lesions (81 % [13/16] vs. 18 % [3/17], respectively, P < 0.001). Irregular/avascular vessel pattern tended to be more common in neoplastic lesions (75 % [12/16] vs. 41 % [7/17], respectively). The surface pattern correctly predicted 82 % of neoplastic lesions, and the vessel pattern correctly predicted 67 % of non-neoplastic lesions. The 2 endoscopic findings together correctly predicted 91 % of neoplastic lesions. Conclusion: Surface pattern, determined by magnifying colonoscopy with NBI, is useful for differenting between UC-associated neoplastic and non-neoplastic lesions.

PMID: 27853744 [PubMed - in process]

TIR-Domain-Containing Adapter-Inducing Interferon-β (TRIF) Regulates CXCR5+ T helper Cells in the Intestine.

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TIR-Domain-Containing Adapter-Inducing Interferon-β (TRIF) Regulates CXCR5+ T helper Cells in the Intestine.

J Clin Cell Immunol. 2016 Oct;7(5):

Authors: Kanagavelu S, Flores C, Hagiwara S, Ruiz J, Hyun J, Cho EE, Sun F, Romero L, Shih DQ, Fukata M

Abstract
OBJECTIVE: Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigen-specific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine.
METHOD: CD4(+)CXCR5(+) T cells, B cells, and plasma cells in the Peyer's patches (PPs) of WT and TRIF-deficient (Trif(LPS2)) mice were analyzed by flow cytometry at the baseline, 9 days post primary infection, and 7 days post-secondary infection with Y. enterocolitica. Y. enterocolitica-specific CD4(+)CXCR5(+) T cells were generated in vitro by co-culturing peritoneal macrophages with splenic naïve T cells in the presence of Y. enterocolitica lysate. WT and Trif(LPS2) mice received CD4(+)CXCR5(+) T cells isolated either from Y. enterocolitica-primed WT mice or generated in vitro. These mice were infected with Y. enterocolitica and followed up to 4 weeks. Y. enterocolitica-specific IgA and IgG were measured in stool and serum samples, respectively.
RESULTS: At baseline, CD4(+)CXCR5(+) T cell proportion was higher but the proportion of B cells and plasma cells was lower in the PPs of Trif(LPS2) mice compared to WT mice. After infection, the proportion of plasma cells also became higher in the PPs of Trif(LPS2) mice compared to WT mice. Corresponding increase of Y. enterocolitica-specific stool IgA but not serum IgG was found in Trif(LPS2) mice compared to WT mice. Both in vivo isolated and in vitro generated CD4(+)CXCR5(+) T cells induced protective immunity against Y. enterocolitica infection.
CONCLUSION: Our results reveal a novel role of TRIF in the regulation of humoral immunity in the intestine that can be utilized as a basis for a unique vaccine strategy.

PMID: 27853628 [PubMed - in process]

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

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Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

Sci Rep. 2016 Nov 17;6:37082

Authors: Becker E, Bengs S, Aluri S, Opitz L, Atrott K, Stanzel C, Castro PA, Rogler G, Frey-Wagner I

Abstract
Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate pro-inflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.

PMID: 27853192 [PubMed - in process]

Non-alcoholic fatty liver disease and colorectal cancer.

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Non-alcoholic fatty liver disease and colorectal cancer.

Postgrad Med J. 2016 Nov 16;:

Authors: Mikolasevic I, Orlic L, Stimac D, Hrstic I, Jakopcic I, Milic S

Abstract
As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%-95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript.

PMID: 27852946 [PubMed - as supplied by publisher]

Prevalence of IgG-4-associated cholangiopathy based on serum IgG-4 levels in patients with primary sclerosing cholangitis and its relationship with inflammatory bowel disease.

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Prevalence of IgG-4-associated cholangiopathy based on serum IgG-4 levels in patients with primary sclerosing cholangitis and its relationship with inflammatory bowel disease.

Turk J Gastroenterol. 2016 Nov;27(6):547-552

Authors: Taghavi SA, Majd SK, Sianati M, Sepehrimanesh M

Abstract
BACKGROUND/AIMS: Autoimmune cholangiopathy is part of a fibro-inflammatory immunoglobulin G-4 (IgG-4)-related systemic disease that causes biliary tract strictures. Its clinical presentation is quite similar to that of more common diseases such as primary sclerosing cholangitis (PSC) and pancreatobilliary malignancies. The aims of the present study were to evaluate the prevalence of IgG-4-associated cholangiopathy (IAC) in patients diagnosed with PSC and its relationship with inflammatory bowel disease (IBD).
MATERIALS AND METHODS: Serum IgG-4 levels were measured in 73 patients. Laboratory data and imaging and endoscopic results were collected from their medical records. The diagnosis of PSC was based on the results of imaging and laboratory data as well as clinical presentation.
RESULTS: Serum IgG-4 levels were elevated in 12 patients (16%); half of these patients had IBD. In the group of patients with normal serum IgG-4 levels, 39 patients (63.9%) had IBD (p=0.364). There were no significant statistical differences between PSC patients with normal and elevated serum IgG-4 levels in terms of age, smoking, presence of IBD, extension and severity of IBD, esophageal and gastric varices, Child and the model for end-stage liver disease (MELD) scores, and anatomical location of the biliary stricture (p>0.05). The prevalence of ascites was higher in patients with elevated serum IgG-4 levels (p=0.029).
CONCLUSION: Compared with previous reports, high serum IgG-4 levels were detected in a higher percentage of patients with a preliminary diagnosis of PSC (12% versus 16%). However, there were no clinical or imaging characteristics that could differentiate PSC patients with normal IgG-4 levels from PSC patients with higher IgG-4 levels.

PMID: 27852547 [PubMed - in process]

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

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Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

Turk J Gastroenterol. 2016 Nov;27(6):525-536

Authors: Can G, Tezel A, Gürkan H, Tozkır H, Ünsal G, Soylu AR, Ümit HC

Abstract
BACKGROUND/AIMS: Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population.
MATERIALS AND METHODS: Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohn's disease patients, 157 ulcerative colitis patients, and 89 healthy controls.
RESULTS: The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohn's disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohn's disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohn's disease. The presence of rs10758669 (AC) was protective against perianal Crohn's disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohn's disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohn's disease and rs11209026 in ulcerative colitis were associated with disease-related operation.
CONCLUSION: This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.

PMID: 27852544 [PubMed - in process]

Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study.

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Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study.

Scand J Gastroenterol. 2016 Nov 17;:1-8

Authors: Huppertz-Hauss G, Høivik ML, Jelsness-Jørgensen LP, Opheim R, Henriksen M, Høie O, Hovde Ø, Kempski-Monstad I, Solberg IC, Jahnsen J, Hoff G, Moum B, Bernklev T

Abstract
OBJECTIVE: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn's disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort.
METHODS: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses.
RESULTS: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p < .001, and CD 17.5 versus 13.3, p < .001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression.
CONCLUSION: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.

PMID: 27852169 [PubMed - as supplied by publisher]

Co-delivery of zinc and 5-aminosalicylic acid from alginate/N-succinyl-chitosan blend microspheres for synergistic therapy of colitis.

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Co-delivery of zinc and 5-aminosalicylic acid from alginate/N-succinyl-chitosan blend microspheres for synergistic therapy of colitis.

Int J Pharm. 2016 Nov 13;:

Authors: Duan H, Lü S, Qin H, Gao C, Bai X, Wei Y, Wu X, Liu M, Zhang X, Liu Z

Abstract
The present study developed novel zinc ion cross-linked alginate/N-succinyl-chitosan (NSC) blend microspheres (MS) for co-delivery of zinc and 5-Aminosalicylic acid (5-ASA) for synergistic therapy of colitis. Physicochemical characterization of blend MS was assessed using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and energy dispersive X-ray spectrometer (EDS). In vitro release studies demonstrated that blend MS has a pH-dependent release property. Both 5-ASA and zinc have lower release in acid medium and higher release in colonic environment. The therapeutic efficacy of zinc cross-linked blend MS was evaluated using induced-colitis rat models, and showed a superior treatment effect in alleviating inflammation of colitis rats. No systemic toxicity was observed after oral administration of blend MS. Therefore, zinc ion cross-linked alginate/N-succinyl-chitosan blend MS appeared to be a good candidate for co-delivery of zinc and 5-ASA to colon, and had great potential application in inflammatory bowel diseases (IBD) treatment.

PMID: 27851980 [PubMed - as supplied by publisher]

Accelerated Infliximab Infusion: Safety, Factors Predicting Adverse Events, Patients' Satisfaction and Cost Analysis. A Cohort Study in IBD Patients.

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Accelerated Infliximab Infusion: Safety, Factors Predicting Adverse Events, Patients' Satisfaction and Cost Analysis. A Cohort Study in IBD Patients.

PLoS One. 2016;11(11):e0166443

Authors: Mazzuoli S, Tricarico D, Demma F, Furneri G, Guglielmi FW

Abstract
BACKGROUND: Standard Infliximab infusion consists of a 2-hour intravenous administration. Recently, Infliximab shortened infusion has been included in the Infliximab label as possible maintenance regimen for patients tolerating Infliximab induction therapy.
AIM: To verify if accelerated 1-hour Infliximab infusions are as safe as standard administrations, in patients with Inflammatory Bowel Disease.
METHODS: Seventy-four patients treated between September 2008 and November 2014 were evaluated. Patients were eligible for 1-hour infusion if they had no history of infusion reactions during the previous 2-hour infusions.
RESULTS: Twenty-three patients received 2-hour infusions, 16 patients received 1-hour infusions, 35 patients received 2-hour infusions followed by 1-hour infusions. A total of 1,123 Infliximab infusions were administered. The proportion of patients experiencing infusion reaction was: 4% over the 1-hour infusions and 9% over the 2-hour (P = 0.318). Adverse reaction/infusion rate was 0.55% over the 1-hour infusions and 0.66% over the 2-hour (P = 0.835). In the logistic model, accelerated infusion was the only statistically significant predictor of infusion reaction risk reduction (-90%; P = 0.024). Mean satisfaction was 8/10 (±0.84) with 1-hour regimen and 6/10 (±0.56) with 2-hour infusions (P = 0.000). The mean total cost was reduced by 47% with the 1-hour regimen (133.54€ and 250.86€ for 1-hour and 2-hour infusions, respectively).
CONCLUSIONS: Accelerated Infliximab infusion does not increase the acute infusion reaction incidence. In patients with inflammatory bowel disease, the 1-hour regimen should be preferred to 2-hour protocol also due to positive effects on indirect costs and patient's satisfaction.

PMID: 27851772 [PubMed - in process]

Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis.

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Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis.

Inflamm Bowel Dis. 2016 Nov 14;

Authors: Zhou Y, Li Y, Zhou B, Chen K, Lyv Z, Huang D, Liu B, Xu Z, Xiang B, Jin S, Sun X, Li Y

Abstract
BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process.
METHODS: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-α and interleukin-2 were examined by Luminex.
RESULTS: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-α and interleukin-2 were also decreased.
CONCLUSIONS: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.

PMID: 27849634 [PubMed - as supplied by publisher]

CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease.

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CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease.

J Immunol. 2016 Nov 14;:

Authors: Kadivar M, Petersson J, Svensson L, Marsal J

Abstract
γδ T cells have been attributed a wide variety of functions, which in some cases may appear as contradictory. To better understand the enigmatic biology of γδ T cells it is crucial to define the constituting subpopulations. γδ T cells have previously been categorized into two subpopulations: CD8αα(+) and CD8(-) cells. In this study we have defined and characterized a novel subset of human γδ T-cells expressing CD8αβ. These CD8αβ(+) γδ T cells differed from the previously described γδ T cell subsets in several aspects, including the degree of enrichment within the gut mucosa, the activation status in blood, the type of TCRδ variant used in blood, and small but significant differences in their response to IL-2 stimulation. Furthermore, the novel subset expressed cytotoxic mediators and CD69, and produced IFN-γ and TNF-α. In patients with active inflammatory bowel disease the mucosal frequencies of CD8αβ(+) γδ T cells were significantly lower as compared with healthy controls, correlated negatively with the degree of disease activity, and increased to normal levels as a result of anti-TNF-α therapy. In conclusion, our results demonstrate that CD8αβ(+) γδ T cells constitute a novel lymphocyte subset, which is strongly enriched within the gut and may play an important role in gut homeostasis and mucosal healing in inflammatory bowel disease.

PMID: 27849165 [PubMed - as supplied by publisher]

Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

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Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

Nat Commun. 2016 Nov 16;7:13386

Authors: Padovani D, Hessani A, Castillo FT, Liot G, Andriamihaja M, Lan A, Pilati C, Blachier F, Sen S, Galardon E, Artaud I

Abstract
Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases.

PMID: 27848965 [PubMed - in process]

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation.

New papers on PubMed -

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation.

Mucosal Immunol. 2016 Nov 16;:

Authors: Arimura K, Takagi H, Uto T, Fukaya T, Nakamura T, Choijookhuu N, Hishikawa Y, Yamashita Y, Sato K

Abstract
Disruption of intestinal homeostasis can lead to inflammatory bowel diseases endowed susceptibility genes and environmental factors affecting intestinal accumulation and activation of colitogenic phagocytes. Plasmacytoid dendritic cells (pDCs) are immune cells that had been proposed to control innate and adaptive immunity through the massive secretion of type I interferon (IFN-I). However, the contribution of pDCs to the progression of intestinal inflammation remains unclear. Here we show a critical role of pDCs in the initiation of acute colonic inflammation using T-cell-independent acute colitis model with a selective ablation of pDCs. Although pDCs accumulated in the inflamed colon upon mucosal injury, deficiency of pDCs attenuated the development of acute colitis independent of IFN-I signaling, accompanied by the diminished colonic production of proinflammatory cytokines. Furthermore, deficiency of pDCs impaired the mobilization of colitogenic phagocytes into the inflamed colon possibly mediated by the abrogated mucosal production of C-C chemokine receptor 2 ligand. Thus, our findings highlight a critical role of pDCs in the induction of the colonic inflammation that regulates the colonic accumulation of inflammatory phagocytes leading to the initiation and exacerbation of acute colitis, and they may serve a key role in controlling gut mucosal immune homeostasis.Mucosal Immunology advance online publication 16 November 2016. doi:10.1038/mi.2016.96.

PMID: 27848952 [PubMed - as supplied by publisher]

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