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.

关键词： inflammatory bowel disease   genetics   myelosuppression   thiopurine  

摘要： IMPORTANCE Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). OBJECTIVE To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). DESIGN, SETTING, AND PARTICIPANTS Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. EXPOSURES Genetic variants associated with TIM. MAIN OUTCOMES AND MEASURES Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 x 10(9)/L or less or a decline in absolute neutrophil cell count to 1.0 x 10(9)/L or less leading to a dose reduction or drug withdrawal. RESULTS Among 1077 patients (398 affected and 679 unaffected;median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years];540 [50%] women;602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients;odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 x 10(-9)). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients;OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 x 10(-8)), which was replicated in a different c

关键词： Chronic fatigue syndrome (CFS)   Myalgic encephalomyelitis (ME)   Inflammatory bowel disease   Oxidative and nitrosative stress (O&NS) pathways   Microbiota-gut-brain interactions   Bacterial translocation   Immunoinflammatory pathways  

摘要： BackgroundSimilarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. This study investigated the risk of incident CFS among patients with *** conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of *** exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012)=2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001;Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR=3.23, 95% CI 2.12-4.91), were older than 35years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR=2.50, 95% CI 1.63-3.84) after *** findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS.

关键词： Clinical trials   Microbiome   Exercise   Body composition  

摘要： Background: Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease. Methods: A randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 +/- 6.5 years and Body Mass Index of 28.9 +/- 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing. Results: Improved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41 mls/kg/min;post-intervention: 46.01 mls/kg/min;p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase;p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the alpha- and beta- diversity of gut microbiota and associated metabolic pathways were evident. Conclusions: Moderate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects.

摘要： The article outlines five facts about inflammatory bowel disease in children and adolescents. Topics include the diagnostic delay common in pediatric inflammatory bowel disease, the occurrence of extraintestinal manifestations of pediatric inflammatory bowel disease before diagnosis, and the relevance of fecal calprotectin testing in the diagnosis.

关键词： Iron deficiency anemia   intravenous iron   Crohn's disease   ulcerative colitis   child   adolescent  

摘要： Objectives: To evaluate the therapeutic response and adverse effects of Noripurum EV (R) in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency *** and methods: Cohort study involving patients with Crohn's disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV (R). Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30 mu g/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100 mu g/l and transferrin saturation <16%. The total dose of Noripurum EV (R) was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic ***: Noripurum EV (R) was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p<.001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0-6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p=.031) than those who did not (31.2%). No adverse events were ***: Noripurum EV (R) in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.