关键词： ACT   Acceptance and Commitment Therapy   ACT-ED   Acceptance and Commitment Therapy plus inflammatory bowel disease education   DASS   Depression Anxiety and Stress Scale   HRQoL   health-related quality of life   IBD   inflammatory bowel disease  

关键词： Nanoparticulate systems   Targeted drug delivery   Inflammatory bowel disease   Inflammation  

摘要： Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory set of conditions that can affect the entire gastrointestinal (GI) tract and is associated with an increased risk of colorectal cancer. To date there is no curative therapy for IBD;therefore life-long medication can be necessary for IBD management if surgery is to be avoided. Drug delivery systems specific to the colon have improved IBD treatment and several such systems are available to patients. However, current delivery systems for IBD do not target drugs to the site of inflammation, which leads to frequent dosing and potentially severe side effects, that can adversely impact patients' adherence to medication. There is a need for novel drug delivery systems that can target drugs to the site of inflammation, prolong local drug availability, improve therapeutic efficacy, and reduce drug side effects. Nanoparticulate (NP) systems are attractive in designing targeted drug delivery systems for the treatment of IBD because of their unique physicochemical properties and capability of targeting the site of disease. This review analyzes the microenvironment at the site of inflammation in IBD, highlighting the pathophysiological features as possible cues for targeted delivery;discusses different strategies and mechanisms of NP targeting IBD, including size-, charge-, ligand-receptor-, degradation- and microbiome-mediated approaches;and summarizes recent progress on using NPs towards improved therapies for IBD. Finally, challenges and future directions in this field are presented to advance the development of targeted drug delivery for IBD treatment. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Topical drug delivery   PLGA   Cyclosporine-A   Crohn's disease   Chronic colitis  

摘要： The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. CYA as incorporated in poly-(lactic-co-glycolic-Acid) (PLGA) nano- and mirocarriers, respectively, each homogeneous in size and providing controlled drug release over 24 h at intestinal pH-value. For comparative reasons, a commercial formulation (Sandimmun Neoral (R)) was included in the study. In an acute model of DSS-induced inflammation in Balb/c mice, up to three doses were administered for each formulation: 50 mg/kg, 25 mg/kg and 12.5 mg/kg. Drug-free particles were included as control. The following parameters were evaluated: body weight, colon length, colon weight/length ratio, cytokine expression and histological analysis. Plasma levels of CYA were analysed to compare systemic bioavailability. While disease parameters, such as, e.g. colon length, always improved with an optimum dose of 25 mg/kg, the commercial and the microparticulate formulations led to measurable plasma levels and adverse effects in terms of body weight loss at the highest dose. In contrast, when administering the same doses as nanoparticles, plasma concentrations remained always below the detection limit, and the body weight of the animals remained unchanged. In conclusion, this study corroborates the potential of nanocarriers enabling an improved topical delivery of CYA to the inflamed gut mucosa after

关键词： AJM300   filgotinib   fingolimod   inflammatory bowel diseases   mongersen   oral therapy   ozanimod   phosphatidylcholine   tofacitinib  

摘要： 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 or 47 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 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 1. 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. T

摘要： The development of new therapies for inflammatory bowel disease is plagued by high costs, potential side effects, and variable levels of effectiveness. Fecal microbial transplant in inflammatory bowel diseases can offer an alternative to traditionally developed pharmacologic therapies and has demonstrated the ability to induce disease remission in randomized control trials. However, questions remain about the ultimate role of this therapy in disease management, including long term safety, and the optimal composition of transplanted stool.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Smoking   Alcohol   Post-operative recurrence  

摘要： In the era of increasing use of immunosuppressive and biologic therapy for inflammatory bowel disease, environmental influences remain important independent risk factors to modify the course of the disease, affect the need for surgery and recurrence rates post-surgical resection. The effect of smoking on inflammatory bowel disease has been established over the decades, however the exact mechanism of how smoking affects remains as area of research. Alcohol is also among the socio-environmental factors which has been recognised to cause a flare of symptoms in inflammatory bowel disease patients. Nonetheless, the exact relation to date is not fully understood, and various paradoxical results from different studies are still a point of controversy. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Psychological functioning   Sleep   Physical activity   Exergaming   Inflammatory bowel diseases   Healthy controls   Peadiatrics  

摘要： People with Inflammatory Bowel Disease (IBD) are at risk for mental health issues, poor sleep quality and limited engagement in physical activity (PA). Standard treatment consists of immune modulating pharmaceuticals though evidence is growing that aerobic exercise training (AET) could serve as an adjuvant option to reduce disease symptoms and improve mental health. The aim of the present exploratory trial was to investigate possible AET effects on psychological functioning, symptoms of depression, sleep and physical activity in paediatric patients with IBD. Twenty-one paediatric patients with IBD and 23 gender- and age-matched healthy controls (HC) were assessed. The IBD group was further split into a "remission-group" (IBD-RE;n = 14) and an "active disease group" (IBD-AD;n = 7). All participants completed an 8-week AET exergame intervention reaching 60-80% of maximum heart rate for 5 days per week. At baseline and after 8 weeks, psychological functioning, depressive symptoms, objective sleep EEG, subjective sleep and objective and subjective PA were assessed. AET improved the exercise capacity of all participants. Self-reported fitness and daily physical activity increased in IBD-AD, but not in IBD-RE and HC. No improvements were observed for psychological functioning, depressive symptoms or subjective sleep. Objective sleep improved, deep sleep increased, light sleep decreased, and in the IBD-AD group the number of arousals after sleep onset decreased. Descriptively, the IBD-AD group reported lower psychological functioning and poorer subjective sleep quality. Among paediatric patients with IBD and healthy controls, an exergaming intervention has the potential to improve exercise capacity, self-reported fitness, daily physical activity, and aspects of objective sleep. Results suggest that children and adolescents in an active state of IBD are at increased risk of poor psychological functioning and poor sleep quality. (C) 2017 Elsevier Ltd. All rights reserved.