Drug Therapy For Inflammatory Bowel Disease Research Articles

FDA-Approved Excipient N, N-Dimethylacetamide Attenuates Inflammatory Bowel Disease in In Vitro and In Vivo Models.

Inflammatory bowel disease (IBD) affects almost 7 million people worldwide and is increasing in incidence. While the precise pathogenesis of IBD remains unknown, the production of inflammatory cytokines and chemokines play a central role. We have previously found that N, N-dimethylacetamide (DMA), a widely used non-toxic drug excipient, suppresses cytokine and chemokine secretion in vitro and prevents inflammation-induced preterm birth in vivo. Using sandwich enzyme-linked immunosorbent assays (ELISAs), we tested whether DMA attenuates cytokine and chemokine secretion from LPS- or TNFα-stimulated human intestinal epithelial cells and human monocytes and HMGB1 release from RAW 264.7 cells. To test our hypothesis that the mechanism of DMA's effects in in vitro and in vivo models of IBD is inhibition of the NF-κB pathway, we used western blotting to track levels of the nuclear factor kappa B (NF-κB) inhibitory molecule I kappa B alpha (IκBα) in THP-1 human monocytes in the absence or presence of DMA. Finally, we induced colitis in C57Bl/6 mice with dextran sodium sulfate (DSS) and then tested whether i.p injections of DMA at 2.1 g/kg/day attenuates clinical and histopathologic signs of colitis. DMA attenuated cytokine and chemokine release from human intestinal epithelial cells and human monocytes and HMGB1 release from RAW 264.7 cells. Importantly, DMA prevented degradation of IκBα in THP-1 cells, thereby suggesting one mechanism for DMA's effects. Finally, we show here, for the first time, that DMA attenuates clinical and histologic features of DSS-induced colitis. Based on these data, DMA should be further explored in preclinical and clinical trials for its potential as novel drug therapy for IBD.

Adherence to treatment in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a common pathology that reduces the quality and duration of a patient’s life. The cornerstone of treatment of IBD patients is polypharmacotherapy based on the use of salicylates, antibiotics, immunomodulatory and biological drugs, and topical dosage forms. Multicomponent treatment has shown to reduce the quality of life and negatively affect adherence to drug therapy in IBD patients.One of the leading causes of treatment failure is low treatment adherence, which leads to disease progression, disability, and increased financial costs. Currently, there are many factors that affect adherence to therapy, some of them are modifiable, which creates opportunities to improve the effectiveness of existing medical interventions. However, the available data on the level of adherence in IBD patients are not numerous and homogeneous, so a low level of adherence to drug therapy in IBD patients is registered in 7–72% of cases.An important issue in understanding adherence in IBD patients is a lack of research on the level of adherence to counselling and lifestyle modification. However, the course of IBD, treatment features related to the duration of therapy and necessary lifestyle modifications (nutrition), as well as regular monitoring of laboratory and instrumental parameters determine the need to assess adherence to lifestyle modification and counselling along with adherence to drug therapy.

MSC therapy for inflammatory bowel disease

Inflammatory bowel disease (IBD) belongs to the group of diseases characterized by idiopathic inflammation of the digestive tract organs. Two basic IBD types are distinguished: ulcerative colitis and Crohns disease. The IBD symptoms including vomiting and diarrhea, abdominal pain, rectal bleeding, anemia have a significant negative impact on the general patients state of health. Besides, IBD patients are susceptible to the risk of a number of serious diseases such as colorectal cancer, thrombosis and primary sclerosing cholangitis. More than 4 million people in the USA and Europe suffer from IBD, with 70000 new cases diagnosed yearly in the USA only.
 In some cases, a surgical removal of the damaged digestive tract fragments is required to treat severe IBD forms. However, drug therapy of IBD has mainly been used in the last decades. The rate of remission with application of traditional IBD therapy is estimated as 20-30%, and is still no higher than 50% with the combined therapy. Cell therapy has been proven to be a very promising approach in the IBD treatment. In our review, we discuss mesenchymal stromal cells (MSC) and the most important preclinical and clinical results of their application for the IBD therapy.

Low prevalence of Helicobacter pylori infection in Chinese Han patients with inflammatory bowel disease

AIM: To investigate the prevalence of Helicobacter pylori (H pylori) infection in Chinese Han patients with inflammatory bowel disease (IBD) and analyze possible associations between H pylori infection and drug therapy for IBD as well as between H pylori infection and the phenotypes of Crohn's disease (CD).

The Prevalence ofHelicobacter pyloriInfection in Korean Patients with Inflammatory Bowel Disease, a Multicenter Study

The prevalence of Helicobacter pylori (H. pylori) infection has been reported to be lower in individuals with inflammatory bowel disease (IBD) in some Western countries. We investigated H. pylori infection in Korean patients with IBD and any possible associations of H. pylori infection with drug therapy for IBD and the phenotype of Crohns disease (CD). We studied 316 unselected patients with IBD, including 169 ulcerative colitis (UC) patients and 147 with CD, and the control group consisted of 316 age- and gender-matched healthy people who received a comprehensive medical examination for a regular checkup purpose. Infection rates of H. pylori as detected by the urea breath test were compared between the IBD patients and the controls. A statistically significant difference in H. pylori infection rate was noticed between the IBD patients (25.3%) and the controls (52.5%; p<0.001), and between UC (32.0%) and CD patients (17.7%; p=0.04). Among the IBD patients, the age group of <60 and individuals with a history of taking metronidazole (13.0%; p=0.038) or ciprofloxacin (6.7%; p=0.001) were found to have a meaningfully lower infection rate, but those who did not take antibiotics still showed H. pylori infection rate significantly lower than the controls (CD 22.0% vs. UC 33.8% vs. Control 52.5%, p<0.001). With an exception of age, phenotypic characteristics showed no significant relations with H. pylori infection rate in CD patients. Korean patients with IBD, particularly CD, were found to have a significantly lower H. pylori infection rate than the controls. This association was more evident in those <60 years old, which suggested that H. pylori infection might be deemed to lower possible risks of IBD in younger adults.

Inflammatory bowel disease: Immunodiagnostics, immunotherapeutics, and ecotherapeutics

Treatment options for inflammatory bowel disease (IBD) reflect a continuing shift from empiricism to strategies based on improved understanding of the pathophysiology of disease. In susceptible individuals, IBD appears to be the result of defective regulation of mucosal immune interactions with the enteric microflora. This has prompted research directed at the interface of the traditional disciplines of immunology, microbiology, and epithelial cell biology. Whereas immunodiagnostics have been of limited clinical value in IBD, assessments of mucosal rather than systemic immune function are promising. Therapeutically, there is an increasing trend toward more aggressive and earlier use of immunomodulatory agents, particularly for prevention of relapse, with cytokine manipulation as a bridge therapy to achieve remission in patients with acute severe disease. Although most drug treatments are directed toward altering the host response, the rationale for manipulating the enteric flora appears sound and will be the basis of additional future therapeutic strategies. Notwithstanding the widening range of options for drug therapy in IBD, other outcome modifiers and well-established principles of managing chronic disease are as important as ever.GASTROENTROLOGY 2001;120:622-635