Project description:To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins. In summary, until now the disease activity is not sufficiently controlled in a relevant fraction of the patients with IBD. Thus, there is an urge for the development of new substances in the therapy of ulcerative colitis and Crohn's disease. Fortunately, new oral and parenteral substances are in the pipeline. This review will focus on oral substances, which have already passed phase II studies successfully at this stage. In this article, we summarize data regarding AJM300, phosphatidylcholine (LT-02), mongersen, ozanimod, filgotinib and tofacitinib. AJM300 and ozanimod were tested in patients with ulcerative colitis and target lymphocyte trafficking through inhibition of the α subunit of integrin, respectively binding to the sphingosine-1-phosphate receptor (subtypes 1 and 5) on lymphocytes. Mongersen was utilized in patients with Crohn's disease and accelerates the degradation of SMAD7 mRNA, which consequently strengthens the mainly anti-inflammatory signalling pathway of transforming growth factor β1. Various Janus kinase (JAK) inhibitors were developed, which inhibit the intracellular signalling pathway of cytokines. For example, the JAK1 blocker filgotinib was tested in Crohn's disease, whereas the JAK1/3 inhibitor tofacitinib was tested in clinical trials for both Crohn's disease and ulcerative colitis. A different therapeutic approach is the substitution of phosphatidylcholine (LT-02), which might recover the colonic mucus. Taken together, clinical trials with these new agents have opened avenues for further clinical studies and it can be expected that at least some of these agents will be finally approved for clinical therapy.
Project description:Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract caused by interactions between genetic, environmental, immunological, and microbial factors. While the incidence and prevalence of IBD in Asian populations were relatively lower than those in Western countries, they appear to be gradually increasing. A Westernized diet, high socioeconomic status, improvement of hygiene, and development of vaccination could affect the increases in IBD incidence and prevalence in Asian countries. This review describes the latest trends in the incidence and prevalence of IBD in Asia. Studying the epidemiology of IBD in Asia may unravel the etiopathogenesis of and risk factors for IBD.
Project description:The burden of inflammatory bowel disease (IBD) in Asia has been increasing over the past decades. Although patients with IBD show heterogenous phenotypes depending on the individual characteristics, no significant differences have been established in the IBD phenotypes of Western and Asian populations. However, despite the much lower incidence of IBD in Asia than in Western countries, the incidence has been rapidly increasing in Asia while remaining stable in Western countries. The incidence of ulcerative colitis (UC) showed an earlier and a more marked increase than the incidence of Crohn disease (CD), but the UC-to-CD ratio has recently decreased because of a relative increase in the incidence of CD in Asia. While CD shows a significant male predominance, UC only shows a slight male predominance. A recent study reported that the incidence of IBD in Asia showed a bimodal age distribution with increasing IBD prevalence, similar to the findings of Western studies. CD in Asian patients, especially those in East Asia, is characterized by ileocolonic involvement and perianal fistula. The frequency of extraintestinal manifestations, including primary sclerosing cholangitis, appears to be lower in Asia, but this finding should be interpreted with caution due to the transient and nonspecific nature of these manifestations. Although familial aggregation is lower in East Asia, it may also be explained by the low prevalence of IBD in Asia. Thus, more studies should focus on the differences in phenotypes in Asian IBD patients versus Western patients.
Project description:T cell subsets are considered central orchestrators of inflammation and homeostasis in the intestine and are established targets for the treatment of inflammatory bowel disease. While approaches aimed at the neutralization of T cell effector cytokines have provided significant benefits for pediatric and adult patients, more recent strategies aimed at inhibiting the infiltration of pathogenic T cell subsets have also emerged. In this review, we describe current knowledge surrounding the function of T cell subsets in pediatric inflammatory bowel disease and outline approaches aimed at targeting T cell trafficking to the intestine which may represent a new treatment option for pediatric inflammatory bowel disease.
Project description:Expression profiling of human colon mucosa samples aquired from inflammatory bowel disease patients and healthy controls. Expression profiling was done using Illumina Human HT-12 arrays, and data analysis was performed using tools from the Bioconductor package
Project description:The prevalence of inflammatory bowel disease (IBD) in childhood is increasing with a phenotype now established as one of complicated and extensive disease. Adolescent patients form a significant proportion of those requiring lifelong care. One of the most important steps in establishing a personal ability to effectively manage chronic disease is appropriate education, communication and a good relationship with healthcare professionals and a successful transition programme and subsequent transfer to adult care underpins this. It is vital to build trust and include parental input while transferring responsibility to the young person Although the literature confirms that the majority of paediatric gastroenterology units now have planned provision for transfer, the quality and appropriateness of these services have not been assessed or audited. This article discusses the drivers for establishing and improving transition services from both the patient's and healthcare provider's perspective. This heterogeneity of provision of healthcare for adolescents needs to be addressed and the experience of young people themselves is good evidence of this need. Barriers to optimal care need to be identified and managed and healthcare providers need to 'buy in' to establishing a flexible, patient focused achievable service for their patient population.
Project description:Samples for microarray analysis were derived from terminal ileum and colonic tissues from probands with Crohn´s disease and Ulcerative Colitis and control patients, respectively. IBD tissue biopsies from non-inflamed regions 10 cm distant from pathological areas were selected. To minimize inter-individual differences in gene expression and to enrich for IBD-specific transcriptional events, 2.5 µg of total RNA from terminal ileum and colon transversum from four individuals of each patient and control group were used for pooling. Keywords = IBD Keywords = Crohn´s disease Keywords = Ulcerative Colitis Keywords: other