多巴胺能系统与炎症性肠病

多巴胺(dopamine,DA)是一种儿茶酚胺类的神经递质.多项研究表明多巴胺能信号通路是促进中枢神经系统和免疫系统之间平衡的关键因素,某些免疫细胞自身可以产生和释放DA.DA受体广泛表达于多种免疫细胞,DA能系统受损可能影响免疫稳态,从而影响自身免疫性疾病的发生和进展.这使得DA和炎症性肠病(inflammatory...     

Pregnancy and inflammatory bowel disease.

Conclusions about the relationship between the pathophysiology and treatment of inflammatory bowel disease and the physiology and management of pregnancy are based on the results of several large physician surveys and retrospective chart reviews. Patients with active disease fare worse than those with inactive disease. There is little evidence that pregnancy affects the course of inflammatory bowel disease or that inactive inflammatory bowel disease affects the course of pregnancy. Judicious medical therapy is effective in controlling inflammatory bowel disease during pregnancy. Sulfasalazine or steroid therapy should not be withdrawn in a patient who needs it to achieve or maintain a quiescent state of inflammatory bowel disease during the course of pregnancy. Immunosuppressive therapy should be avoided. Aggressive medical therapy with total parenteral nutrition in a team approach with a gastroenterologist, surgeon, and perinatologist usually avoids the need for surgical intervention during pregnancy with a good fetal outcome in a patient whose disease is active. Contraception against pregnancy need only be considered in those patients whose disease is so severe that operative therapy is imminent.     

Ultrastructural study of inflammatory bowel disease.

Ultrastructural changes that occurred in chronic active ulcerative colitis and Crohn's disease were investigated and compared to normal as well as to higher grades of dysplasia in adenomas and carcinomas. A greater number of immature absorptive cells, undifferentiated and intermediate cells were seen as compared to normal. One case of Crohn's and two cases of chronic ulcerative colitis including one with coexisting carcinoma showed increased number of vesicles and electron-dense bodies (EDB) in the absorptive cells and increased heterogeneity of mucin droplets in goblet cells and presence of atypical secretory cells (ASC). Higher grades of dysplasia characterised by large numbers of atypical secretory cells were not seen in the present series and provide no relationship between the atypical ultrastructural features and increased risk of malignancy. However, the number of cases investigated is too small and a large series is required to clarify the significance of observations such as increased number of electron-dense bodies and vesicles in the apical cytoplasm and presence of atypical secretory cells.     

Cyclosporine and inflammatory bowel disease: buying time.

Cyclosporine is an effective drug in acute exacerbations of corticosteroid resistant ulcerative colitis, but its efficacy to maintain disease remission is not clear. Cyclosporine may not be as effective in Crohn''s disease. However, being a rapidly acting immunosuppressant, cyclosporine may be a valuable therapeutic option in the short-term to treat corticosteroid resistant Crohn''s disease and ulcerative colitis.     

Chronic inflammatory bowel disease in childhood.

The diagnosis of Crohn''s disease in childhood has been facilitated by the use of fibreoptic endoscopy with biopsies, complemented by double-contrast radiology. Clinical suspicion leads initially to several relevant blood tests. These are followed by endoscopy and multiple colonic biopsies or barium follow-through studies depending on whether large-bowel or small-bowel disease is suspected. The present approach to diagnosis is based on corroborative investigative techniques-endoscopy, radiology, and histology, The availability of paediatric colonoscopes of small diameter should make it possible for paediatricians to perform limited examinations, but when more extensive endoscopy is indicated the child should be referred to special centres.     

Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad

The complex interaction of genetic, microbial, and environmental factors may result in continuous activation of the mucosal immune system leading to inflammatory bowel disease (IBD). Most present treatments for IBD involve altering or suppressing the aberrant immune response; however, the role of the intestinal microbiota in the pathophysiology of IBD is becoming more evident. The epithelial layer is essential for the proper functioning of the gastrointestinal tract, and its increased permeability to the luminal antigens may lead to the inflammatory processes and mucosal damage observed in IBD. Factors affecting the efficacy of the epithelial barrier include presence of pathogenic bacteria (e.g., Helicobacter spp.), presence of probiotic bacteria, availability of selected nutrients, and others. Defective function of the mucosal barrier might facilitate the contact of bacterial antigens and adjuvants with innate and adaptive immune cells to generate prolonged inflammatory responses. This review will briefly describe the complex structure of the epithelial barrier in the context of bacterial-mucosal interactions observed in human IBD and mouse models of colitis.     

Hypoxia and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a general term to describe inflammatory diseases of the gastrointestinal tract such as Crohn's disease and ulcerative colitis. IBD affects approximately 1 in 200 individuals and exerts a significant health and quality of life burden on patients. Surgical intervention can be curative in ulcerative colitis but there is currently no cure for Crohn's disease. Since this is the case, and the fact that patients are often diagnosed at a young age, IBD exerts a significant financial burden on the health care system, and society as a whole.The underlying pathology of IBD is complex and involves a combination of genetic, environmental and microbial factors. Regardless of the underlying causes of the condition, this disease is universally characterized by disruption to the protective epithelial barrier separating the intestinal lumen above from the mucosal immune system below. Once this barrier becomes compromised a sequence of events ensues, that can occur in repetitive cycles to ensure long-term and serious damage to the gut.The role of hypoxia and hypoxia-dependent signalling pathways are increasingly appreciated to play a role in the physiology and pathophysiology of the intestine. The intestinal epithelium normally exists in a state of physiological hypoxia, with additional tissue hypoxia a feature of active inflammatory disease. Furthermore, recent pre-clinical animal studies have clearly supported the rationale for pharmacologically manipulating the oxygen-sensitive hypoxia-inducible factor (HIF) pathway in models of IBD. Thus, this review will discuss the contribution of hypoxia sensitive pathways in the pathology of IBD. Finally we will discuss the emerging evidence for manipulation of hypoxia-sensitive pathways in the treatment of IBD.     

Cytokines in inflammatory bowel disease

Over the past decade, much has been learned regarding the role of various cytokines in the pathogenesis of inflammatory bowel disease. Several cytokine 'knockout' models in mice have been shown to develop colitis, while alterations in the production of various cytokines has been documented in human Crohn's disease and ulcerative colitis. In recent years, attempts have been made to treat these diseases through modulation of cytokine production or action. This review focuses on the cytokines that have been implicated in the pathogenesis of inflammatory bowel disease. The evidence for and against a role for particular cytokines in intestinal inflammation is reviewed, as is the experimental and clinical data suggesting that cytokines are rational targets for the development of new therapies.     

Somatostatin in inflammatory bowel disease

Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed.     

Nematode modulation of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease arising due to a culmination of genetic, environmental, and lifestyle-associated factors and resulting in an excessive pro-inflammatory response to bacterial populations in the gastrointestinal tract. The prevalence of IBD in developing nations is relatively low, and it has been proposed that this is directly correlated with a high incidence of helminth infections in these areas. Gastrointestinal nematodes are the most prevalent parasitic worms, and they efficiently modulate the immune system of their hosts in order to establish chronic infections. Thus, they may be capable of suppressing unrelated inflammation in disorders such as IBD. This review describes how nematodes, or their products, suppress innate and adaptive pro-inflammatory immune responses and how the mechanisms involved in the induction of anti-nematode responses regulate colitis in experimental models and clinical trials with IBD patients. We also discuss how refinement of nematode-derived therapies should ultimately result in the development of potent new therapeutics of clinical inflammatory disorders.