关键词： immunosuppressant   inflammatory bowel disease   melanoma skin cancer   nonmelanoma skin cancer   skin cancer   thiopurines  

摘要： Background and Aim The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients. Methods MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity. Results Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance. Conclusion Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.

关键词： Cannabinoid   JTE907   Lymphocytes   Treg   Colitis  

摘要： Cannabinoids are known to possess anti-inflammatory and immunomodulatory properties, but the mechanisms involved are not fully understood. CB2 is the cannabinoid receptor that is expressed primarily on hematopoietic cells and mediates the immunoregulatory functions of cannabinoids. In order to study the effect of JTE907, a selective/inverse agonist of CB2 with anti-inflammatory properties, on the differentiation of T cell subtypes, we used an in vitro system of Th lineage-specific differentiation of naive CD4(+) T lymphocytes isolated from the mouse spleen. The results indicate that JTE907 was able to induce the differentiation of Th0 cells into the Treg cell phenotype, which was characterized by the expression of FoxP3, TGF-beta and IL-10. P38 phosphorylation and STAT5A activation were found to mediate the signaling pathway triggered by JTE907 via the CB2 receptor in Th0 lymphocytes. In mice with DNBS-induced colitis, JTE907 treatment was able to induce an increase in the number of CD4(+) CD25(+) FoxP3(+) cells in the lamina propria after 24 h of disease onset and reduce disease severity after 48 h. Further, longer JTE907 treatment resulted in less severe colitis even when administered orally, resulting in less body weight loss, reduction of the disease score, prevention of NF-kappa B activation, and reduction of the expression of adhesion molecules. Collectively, the results of this study indicate that specific signals delivered through the CB2 receptor can drive the immune response towards the Treg cell phenotype. Thus, ligands such as JTE907 may have use as potential therapeutic agents in autoimmune and inflammatory diseases.

关键词： abdominal pain   anhedonia   BDI-II   Crohn's disease   depression   IBS-SSS   inflammatory bowel disease   irritable bowel syndrome   Rome IV criteria   SHAPS   ulcerative colitis  

摘要： Background Anhedonia is the lowered ability to experience pleasure from rewarding or enjoyable activities and is considered a symptom of depression. Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are frequently accompanied by psychiatric disorders such as depression. However, to our knowledge, studies have yet to investigate the anhedonia in these patients. Our aim was to study the level of anhedonia in patients with IBD and IBS in comparison with healthy controls (HC), and to relate anhedonia levels with the severity of abdominal pain. Methods We consecutively recruited IBD and IBS patients. All patients fulfilled the Snaith-Hamilton Pleasure Scale (SHAPS), a self-rating scale consisting of 14 items that cover the domains of social interaction, food, and drink, sensory experiences, achievement and pastimes, and the Beck Depression Inventory-II (BDI-II) to screen for depression. Moreover, we calculated abdominal pain on a (0-100) Visual Analog Scale (VAS) in all patients. Key Results We enrolled 120 patients (64 IBD and 56 IBS) and 81 HC. Among IBD patients, 34 had Crohn's disease and 30 ulcerative colitis. All patients as a whole had significantly higher SHAPS and BDI-II scores than HC (1.3 +/- 1.5 vs 0.8 +/- 0.1;P = 0.01 and 10.4 +/- 7.5 vs 5.9 +/- 4.9;P < 0.001, respectively), while no significant differences were found among groups. SHAPS score showed a significant correlation in only a few statements of BDI-II. In our cohort, a multivariate regression analysis showed that SHAPS score was significantly related to current abdominal pain (0-100 VAS) (P = 0.03) independent of gender and age. Conclusions and Inferences The level of anhedonia was higher in all patients compared to healthy controls. The more the subject is anhedonic, the higher the VAS scale for abdominal pain. This study suggests that anhedonia would need to be very carefully weighed in IBD and IBS patients.

关键词： children   Crohn's disease   origin   prevalence   ulcerative colitis  

摘要： Background The incidence and prevalence trends of inflammatory bowel disease (IBD) vary between developed and developing countries. Aim To investigate the prevalence and associated sociodemographic factors of IBD in Israeli Jewish adolescents Methods The files of the army medical corps were reviewed for adolescents recruited in 2002-2016 with confirmed IBD. Covariate data included birth date, patient and parental country of birth, number of children in the household, age at diagnosis, and socioeconomic status. Findings were compared with the remaining recruits without IBD. Results Of the 1,144,213 adolescents recruited, 2372 (0.2%) had IBD (Crohn's disease, 68%). Median age of the cohort was 17.1 years (interquartile range, 16.9-17.3). Over the study period, the annual point prevalence per 100,000 examinees significantly increased: total IBD, 58 to 373;Crohn's disease, 42 to 425;ulcerative colitis, 16 to 128. Mean age at IBD diagnosis decreased from 15.0 +/- 2.8 years in 2002-2008 to 14.3 +/- 3.1 years in 2009-2016 (P < 0.0001). Significance was maintained on separate analyses of Crohn's disease and ulcerative colitis. Both diseases were significantly less prevalent in subjects from families with at least one parent born in a developing country and >= 3 children. There was a significant association of lower socioeconomic status with lower prevalence of Crohn's disease (odds ratio 0.41, 95% confidence interval, 0.31-0.54) and ulcerative colitis (odds ratio 0.25, 95% confidence interval, 0.15-0.42). Conclusions The point prevalence of Crohn's disease and ulcerative colitis in Israeli Jewish adolescents increased six-fold and eight-fold, respectively, over 15 years along with a decrease in age at diagnosis.

关键词： CD   Crohn's disease   CLE   confocal laser endomicroscopy   IBD   inflammatory bowel disease   UC   ulcerative colitis  

关键词： autoimmunity   human   inflammation   mucosa   mucosal immunity   neutrophils   T Cells  

摘要： Inflammatory bowel disease (IBD) is characterized by activation of both the innate and adaptive immune system in genetically susceptible individuals, resulting in chronic intestinal inflammation. The triggers that initiate and perpetuate this continuous inflammation are the subject of much speculation and research, although the central role of the intestinal microbiota is recognized, and is even a target for treatment in some circumstances. The mainstay of modern IBD treatment is suppression of the immune response towards as yet unspecified antigens, and conventional therapy includes corticosteroids, 5-aminosalicylic acid (5-ASA), thiopurines and methotrexate. Reducing activity of specific mediators has proven efficacious, including adhesion molecules, such as the gut-homing integrin alpha(4)beta(7) expressed on the surface of circulating immune cells, and cytokines, such as tumour necrosis factor alpha (TNF-alpha). This has been achieved using biologic agents including monoclonal antibodies. Recent discoveries in immunology and neuroscience have revealed that signals in the peripheral nervous system regulate inflammation, including levels of TNF-alpha. The understanding of the mechanisms of the neuro-immune communication involved in inflammation control in the gut is evolving, but is as yet incomplete. Clinical studies using implanted vagus nerve stimulators for treatment of IBD show encouraging results. Accordingly, the neural reflex control of inflammation is emerging as a potential therapeutic target in treatment of IBD. Here, we review current therapeutic options and neural reflex control of gut immunity in the context of intestinal inflammation.

关键词： cannabidiol   Crohn disease   marijuana   ulcerative colitis  

摘要： Objectives: The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD). Methods: A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children's Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use. Results: The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 +/- 9 times;and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain. Conclusions: Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.

关键词： Amines   Anatomy   Biochemistry   Biogenic amines   Biology and life sciences   Catecholamines   Chemical compounds   Chemistry   Digestive system   Dopamine   Gastroenterology and hepatology   Gastrointestinal tract   Genetic mapping   Genetics   Genotyping   Heredity   Hormones   Inflammatory bowel disease   Medicine and health sciences   Molecular biology   Molecular biology techniques   Molecular genetics   Neurochemistry   Neuroscience   Neurotransmitters   Nucleotide sequencing   Organic chemistry   Organic compounds   Physical sciences   Proteins   Research and analysis methods   Research Article   Sequencing techniques   Serum proteins   Variant genotypes  

摘要： Inflammatory bowel diseases (IBD) are associated with altered neuronal regulation of the gastrointestinal (GI) tract and release of norepinephrine (NE). As sympathetic innervation of the GI tract modulates motility, blood flow, and immune function, changes in NE signaling may alter the risk of developing IBD. Dopamine beta-hydroxylase (D beta H), the enzyme responsible for NE production, has been suggested to play a critical role in IBD, however the exact mechanism is unknown. We hypothesized that genetic variants of D beta H could increase the risk of IBD. We performed genetic analysis on 45 IBD patients and 74 controls. IBD patients were screened by targeted exome sequencing and compared with NeuroX D beta H single nucleotide polymorphism (SNP) genotyping data of the controls. Serum D beta H protein levels for 15 IBD patients and 13 controls were evaluated using immunoblots and competitive ELISA. Seven SNPs were observed from D beta H targeted exome sequencing in the 45 IBD patients. A single non-synonymous SNP, rs6271 (Arg549Cys), had a significant association with IBD patients;the odds ratio was a 5.6 times higher SNP frequency in IBD patients compared to controls (p = 0.002). We also examined the function and availability of the protein in both the IBD and control patients' sera bearing D beta H Arg549Cys. Both control and IBD subjects bearing the heterozygote allele had statistically lower D beta H protein levels while the intrinsic enzyme activity was higher. This is the first report of a noradrenergic genetic polymorphism (rs6271;Arg549Cys) associated with IBD. This polymorphism is associated with significantly lower levels of circulating D beta H.

关键词： Anatomy   Biology and life sciences   Colitis   Colon   Cytokines   Developmental biology   Digestive system   Gastroenterology and hepatology   Gastrointestinal tract   Histology   Immune physiology   Immune system   Immunology   Inflammatory bowel disease   Innate immune system   Lymph nodes   Lymphatic system   Medicine and health sciences   Microbiology   Molecular development   Physiology   Probiotics   Research Article   Ulcerative colitis  

摘要： Recent studies have demonstrated the immunomodulatory effects of heat-killed lactic acid bacteria. The aim of this study was to evaluate the protective effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on a model of inflammatory bowel disease (IBD). A total of 28 female NC/Nga mice were divided into 4 treatment groups. Controls were fed a normal commercial diet. In the experimental groups, colitis was induced by rectal administration of dinitrobenzene sulfonic acid. Two groups were orally administered 2 and 17 mg/kg EF2001, respectively. EF-2001 treatment decreased the expression of several cytokines, including cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), interferon (IFN)-gamma, interleukin (IL)-1 beta, and IL-6 in inflamed colon compared to the DNBS alone group. In addition, EF-2001 suppressed DNBS-induced colonic tissue destruction. Therefore, this study strongly suggests that EF-2001 could alleviate the inflammation associated with mouse IBD.