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Eudragit E as coating material for the pH-controlled drug release in the topical treatment of inflammatory bowel disease (IBD).

During an attack of ulcerative colitis the colonic pH of normally 6.4-7.0 drops to values of 2.3-4.7. The objective of this study was to investigate an acid-soluble polymer (Eudragit E) as coating material for multiple units (mini tablets) with regard to its ability to allow drug release only under the acidic conditions of the inflamed colon. Mini tablets (diameter 3 mm) containing 20% (w/w) of the model drug dexamethasone with or without the mucoadhesive swelling agent carbomer 934 (neutralized) were coated in a small coating pan with different amounts of an organic solution of Eudragit E leading to coating thicknesses of 150-400 microm. Drug release from the Eudragit E-coated cores at pH 2.0-5.0 starts after 10-50 min due to the rapid dissolution of the Eudragit E film. At pH 6.8 lag times of drug release depend on the composition of the cores and the thickness of the coating film: In the case of the carbomer-containing cores drug release is induced by disruption of the coating film due to swelling of the cores and lag times (up to 20 h) increase overproportionately with increasing coating thickness. With no swelling agent in the cores drug release at pH 6.8 is delayed due to the low erosion/dissolution rate of Eudragit E. Lag times of drug release (up to 33 h) increase in a linear manner with increasing coating thickness. Thus, Eudragit E, protected against dissolution in the stomach by an enteric coating, is a suitable coating polymer for drug release in acidic regions such as the inflamed colon.

Administration, Topical↗

Diagnostic approach to IBD.

Inflammatory bowel disease, with Crohn's disease and ulcerative colitis as the two main disorders, is a heterogeneous group of disorders of unknown etiology. Clinical initial presentation is sometimes misleading and causing diagnostic delay which may be important. Identification of subgroups of patients on the basis of genetic, immunologic and clinical markers will be important for exact diagnosis, but also for new drug trials. The current diagnosis depends on clinical, radiographic, endoscopic and laboratory data. The introduction of serological markers such as pANCA and ASCA will allow an increase in the diagnostic accuracy at initial diagnosis of inflammatory bowel disease and may play a role in defining subgroups of the disease.

Barium Sulfate↗

Difficult differential diagnoses in IBD: ileitis and indeterminate colitis.

When considered in the appropriate clinical scenarios, the diagnoses of Crohn's disease or ulcerative colitis are usually straightforward. Most cases can be definitively diagnosed by the typical subacute or chronic history of symptoms, and radiographic, endoscopic, and histologic confirmation in the presence of negative stool studies; newer serologic assays are now available and are of value if the diagnosis remains uncertain. In this paper, we review distinguishing features in the diagnosis of ileitis and the distinction to be made in conclusively diagnosing ulcerative vs. Crohn's colitis.

Adult↗

Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD.

6-mercaptopurine (6-MP) and its parent drug azathioprine (AZA) have been proven to be effective for both steroid-dependent and chronically active, or steroid-resistant inflammatory bowel disease, as well as for the prevention of relapse. Concerns about toxicity, delayed onset of action, and therapeutic failure (1 out of 3 patients) have restricted their use. Recent pharmacogenetic advances have led to the development of novel strategies to optimize and individualize therapy with AZA and 6-MP, maximizing efficacy while minimizing toxicity. We have defined a range of optimal therapeutic 6-MP metabolite levels, as well as an association of metabolite levels with medication-induced toxicity and the genotype of the main catabolic enzyme, thiopurine methyltransferase (TPMT). Measurement of 6-MP metabolite levels and TPMT molecular analysis provide clinicians with useful tools for optimizing therapeutic response to 6-MP/AZA, as well as for identifying individuals at increased risk for drug-induced toxicity.

Antimetabolites↗

Mucosal T cells as a target for treatment of IBD.

Interleukin-7 (IL-7) is an indispensable cytokine for the development of lymphocyte lineage cells. However, the potential role of IL-7 in peripheral nonlymphoid tissues was unclear before our study. We have demonstrated that intestinal epithelial cells produce IL-7 and that IL-7 serves as a regulatory factor for proliferation of mucosal lymphocytes expressing IL-7 receptor (IL-7R). Recent studies demonstrated that intestinal epithelial cell-derived IL-7 plays a crucial role in the organization of mucosal lymphoid tissues and regulating the normal immune response in intestinal mucosa. In a previous study, we demonstrated that IL-7 transgenic mice developed chronic colitis. Here, we have demonstrated the essential role of mucosal IL-7/IL-7R-dependent signals in the development of chronic intestinal inflammation. Our results indicate that mucosal IL-7/IL-7R-dependent signals are involved in the development of chronic intestinal inflammation in both the mouse model and human disease of the intestinal mucosa. Therefore, current studies indicate that therapeutic approaches by specific targeting of IL-7R-expressing mucosal T cells may be feasible in the treatment of human ulcerative colitis.

Animals↗