Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cyt...Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.展开更多
The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease （IBD） and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycop...The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease （IBD） and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein （P-gp） functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom （i.e. glucocorticoids） central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract （G-I） with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdrl knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a metaanalysis of the available findings obtained with two SNPs polymorphism （C3435T and G2677T/A） in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC （OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively）. In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.展开更多
This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had b...This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.展开更多
文摘Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.
基金Supported by a grant from the Health Minister of Health N°RF03GA01,RC0503GA20
文摘The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease （IBD） and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein （P-gp） functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom （i.e. glucocorticoids） central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract （G-I） with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdrl knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a metaanalysis of the available findings obtained with two SNPs polymorphism （C3435T and G2677T/A） in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC （OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively）. In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.
文摘This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.
