Browsing by Subject "Ulcerative colitis"

Now showing 1 - 8 of 8
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    Effector T Helper Cell Subsets in Inflammatory Bowel Diseases
    (Frontiers Media, 2018-06-01) Imam, Tanbeena; Park, Sungtae; Kaplan, Mark H.; Olson, Matthew R.; Pediatrics, School of Medicine
    The gastrointestinal tract is a site of high immune challenge, as it must maintain a delicate balance between tolerating luminal contents and generating an immune response toward pathogens. CD4+ T cells are key in mediating the host protective and homeostatic responses. Yet, CD4+ T cells are also known to be the main drivers of inflammatory bowel disease (IBD) when this balance is perturbed. Many subsets of CD4+ T cells have been identified as players in perpetuating chronic intestinal inflammation. Over the last few decades, understanding of how each subset of Th cells plays a role has dramatically increased. Simultaneously, this has allowed development of therapeutic innovation targeting specific molecules rather than broad immunosuppressive agents. Here, we review the emerging evidence of how each subset functions in promoting and sustaining the chronic inflammation that characterizes IBD.
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    Gastrointestinal complications after kidney transplantation
    (Baishideng Publishing Group Inc., 2020-10-14) Gioco, Rossella; Corona, Daniela; Ekser, Burcin; Puzzo, Lidia; Inserra, Gaetano; Pinto, Flavia; Schipa, Chiara; Privitera, Francesca; Veroux, Pierfrancesco; Veroux, Massimiliano; Surgery, School of Medicine
    Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease (IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.
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    Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis
    (Springer, 2015-12) Masuoka, Howard C.; Vuppalanchi, Raj; Deppe, Ross; Bybee, Phelan; Comerford, Megan; Liangpunsakul, Suthat; Ghabril, Marwan; Chalasani, Naga; Department of Medicine, IU School of Medicine
    BACKGROUND AND AIM: Hepatocyte apoptosis or necrosis from accumulation of bile salts may play an important role in the disease progression of primary sclerosing cholangitis (PSC). The aim of the current study was to measure serum markers of hepatocyte apoptosis (cytokeratin-18 fragments--K18) and necrosis (high-mobility group protein B1--HMGB1) in adults with PSC and examine the relationship with disease severity. METHODS: We measured serum levels of K18 and HMGB1 in well-phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was assessed biochemically, histologically, and PSC Mayo risk score. Quantification of hepatocyte apoptosis was performed using TUNEL assay. RESULTS: The mean age of the study cohort was 49.7 ± 13.3 years and comprised of 67% men and 93% Caucasian. Serum K18 levels were significantly higher in the PSC patients compared to control (217.4 ± 78.1 vs. 157.0 ± 58.2 U/L, p = 0.001). However, HMGB1 levels were not different between the two groups (5.38 ± 2.99 vs. 6.28 ± 2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total bilirubin (r = 0.61, p ≤ 0.001), and albumin (r = -0.4, p = 0.02). Serum K18 levels also correlated with the level of apoptosis present on the liver biopsy (r = 0.8, p ≤ 0.001) and Mayo risk score (r = 0.4, p = 0.015). CONCLUSION: Serum K18 but not HMGB1 levels were increased in PSC and associated with severity of underlying liver disease and the degree of hepatocyte apoptosis.
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    Inflammatory bowel disease: Looking beyond the tract
    (SAGE, 2019) Chams, Sana; Badran, Reina; Sayegh, Skye El; Chams, Nour; Shams, Ali; Hajj Hussein, Inaya; Medicine, School of Medicine
    Inflammatory bowel disease is a chronic inflammatory condition that encompasses Crohn's disease and ulcerative colitis. Inflammatory bowel disease is not exclusive to the gastrointestinal system, as it has been identified to be associated with extraintestinal manifestations that encompass every other organ system in the human body. This review article will comprehensively review the current knowledge on extraintestinal manifestations of inflammatory bowel disease. In addition, it will discuss the recommendations for screening and surveillance for extraintestinal manifestations in these patients since early appropriate diagnosis is imperative in preventing morbidity and cancer development.
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    MicroRNA in inflammatory bowel disease: Translational research and clinical implication
    (Baishideng Publishing Group Co, 2015-11-21) Fisher, Kurt; Lin, Jingmei; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Idiopathic inflammatory bowel disease (IBD) predominantly includes ulcerative colitis and Crohn's disease. The pathogenesis of IBD is complex and not completely understood. MicroRNAs belong to a class of noncoding small RNAs that post-transcriptionally regulate gene expression. Unique microRNA expression profiles have been explored in IBD. In this review, we focus on the unique microRNA expression pattern in both tissue and peripheral blood from IBD patients and emphasize the potential diagnostic and therapeutic applications. The discovery of microRNAs has contributed to our understanding of IBD pathogenesis and might lead to clinical advance in new therapeutics.
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    Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model
    (Baishideng Publishing Group, 2018-07-28) Qi, Qin; Liu, Ya-Nan; Jin, Xiao-Ming; Zhang, Lin-Shuang; Wang, Cun; Bao, Chun-Hui; Liu, Hui-Rong; Wu, Huan-Gan; Wang, Xiao-Mei; Anatomy and Cell Biology, School of Medicine
    AIM: To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis. METHODS: A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls (HC), ulcerative colitis model group (UC), UC with 7 d of moxibustion (UC-7), UC with 14 d of moxibustion (UC-14), UC with mesalazine gavage (UC-W), HC with 7 d of moxibustion (HC-7), HC with 14 d of moxibustion (HC-14). Moxibustion was applied to the bilateral Tianshu (ST25). Gut microbiome profiling was conducted by 16S rRNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS: Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term (7 d) but no longer term (14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12 (IL-12) (P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, IgA, tumour necrosis factor-α and its receptors 1 (TNFR1) and TNFR2 (P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10 (P < 0.01) and transforming growth factor-β (P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion. CONCLUSION: Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity.
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    The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis
    (Taylor & Francis, 2017-11-02) Qazi, Taha; Amaratunga, Thelina; Barnes, Edward L.; Fisher, Monika; Kassam, Zain; Allegretti, Jessica R.; Medicine, School of Medicine
    Several studies have suggested worsening in inflammatory bowel disease (IBD) activity following fecal microbiota transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity. Results: Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10–21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13–36%)) was higher compared with FMT for IBD (11.1% (95% CI 7–17%)). Rates of worsening in IBD after lower GI FMT delivery revealed a higher rate of worsening in IBD activity (16.5% (95% CI: 11–24%)) compared with upper GI delivery (5.6% (95% CI: 2–16%)). Rates of worsening in high quality studies and randomized controls trials (RCTS) suggested a marginal risk of worsening in IBD activity (4.6%, (95% CI: 1.8–11%). Rates of IBD worsening are overall marginal across high quality RCTS. It is unknown if the FMT itself led to the worsening of IBD in this small fraction or if this represents alternative etiologies.
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    Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response
    (Springer Nature, 2019-01-03) Haberman, Yael; Karns, Rebekah; Dexheimer, Phillip J.; Schirmer, Melanie; Somekh, Judith; Jurickova, Ingrid; Braun, Tzipi; Novak, Elizabeth; Bauman, Laura; Collins, Margaret H.; Mo, Angela; Rosen, Michael J.; Bonkowski, Erin; Gotman, Nathan; Marquis, Alison; Nistel, Mason; Rufo, Paul A.; Baker, Susan S.; Sauer, Cary G.; Markowitz, James; Pfefferkorn, Marian D.; Rosh, Joel R.; Boyle, Brendan M.; Mack, David R.; Baldassano, Robert N.; Shah, Sapana; Leleiko, Neal S.; Heyman, Melvin B.; Grifiths, Anne M.; Patel, Ashish S.; Noe, Joshua D.; Aronow, Bruce J.; Kugathasan, Subra; Walters, Thomas D.; Gibson, Greg; Thomas, Sonia Davis; Mollen, Kevin; Shen-Orr, Shai; Huttenhower, Curtis; Xavier, Ramnik J.; Hyams, Jeffrey S.; Denson, Lee A.; Pediatrics, School of Medicine
    Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.