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NCX-456, but not mesalamine, administration resulted in a marked reduction in clinical, histological, and immunologic signs of colitis in both models. NCX-456 inhibited the release of T-helper type 1-derived cytokines and increased the release of the regulatory T cell-derived cytokines interleukin 10 and transforming growth factor beta. In vitro analyses showed that NCX-456 inhibited proliferation and caused selective apoptosis of the subset of activated lamina propria T-helper type 1 cells, whereas it was ineffective for regulatory T-cell function and survival.
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Between January 1988 and December 1989 a total of 60 patients (37 men, 23 women, mean age 34.8 years) were selected in whom the diagnosis of Crohn's disease had been known for at least 2 years. A further criterion for inclusion was remission for at least one year in patients who had been operated or for one month in the nonoperated ones. Furthermore, the latter must have had at least one recurrence during the last year. They were in turn assigned to be treated with 5-ASA (2.4 g daily by mouth) or not treated (control). The activity and localization of Crohn's disease were defined according to the "Crohn's disease activity index" (CDAI) and the "laboratory index" (LI), as well as by endoscopy and (or) radiology. The patients were examined every 6 months for 4 years. A recurrence was diagnosed if the CDAI was more than 150 or had increased to at least 60 points above the initial value and the LI was above 100.
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The mean decline in ECC of 0.3 mL/min/yr in patients with CD does not exceed the decline expected from physiologic aging. Furthermore, the cumulative dose of 5-ASA was not a predictor for change in renal function. However, as interstitial nephritis caused by 5-ASA may rarely occur, we still advocate measurements of serum creatinine before and during treatment.
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In the present study, hydroxypropyl methyl cellulose grafted with polyacrylamide (HPMC-g-PAM) hydrogel was evaluated in vitro as a potential carrier for controlled release of 5-amino salicylic acid (5-ASA). The graft copolymer was developed by grafting PAM chains onto HPMC backbone using potassium persulphate as initiator. The swelling behaviour of hydrogel based tablet was investigated as a function of pH and time in various buffer solutions similar to that of gastric and intestinal fluids. The % equilibrium swelling was found to be higher in case of simulated intestinal fluid (pH=7.4) and lower in simulated gastric fluid (pH=1.2), making an ideal matrix as required for colon specific drug delivery. The drug release study was performed at various pH values akin to the condition of GI tract. The release kinetics of 5-ASA showed non-Fickian diffusion behaviour. This indicates that the release is controlled by a combination of polymer relaxation or erosion of the matrix and diffusion of the drug from the swollen matrix.
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Nonadherence occurred in 102 of 356 participants (28.7%). Adherence increased significantly with more aggressive therapies (median Medicine Adherence Report Scale: 5-aminosalicylates 18, thiopurines 19, biological 20; P < 0.0001). Nonadherence was not associated with anxiety and depression or disease-related patient knowledge. Adherent patients had significantly higher belief of necessity for medication (P < 0.0001) and a trend toward lower concerns about medication (P = 0.08). Membership of an IBD patient organization was associated with better adherence (P < 0.0001). Concerns about medication rose significantly with more aggressive therapies (P = 0.009), but belief of necessity was similar for all medications.
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Orofacial manifestations of Crohn's disease can be difficult to diagnose and treat. We report a case in which the orofacial lesions occurred 7 years prior to the diagnosis of underlying inflammatory bowel disease. The patient was refractory to mesalamine and systemic corticosteroids but responded to infliximab, the chimeric monoclonal antibody to tumor necrosis factor (TNF-alpha). A review of the literature of the orofacial granulomatoses is presented as well.
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Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study.
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Mesalamine resulted in a dose-dependent decrease in PN-induced apoptosis, whether mesalamine was administered before (>10 micromol/L; IC50, 16 micromol/L), simultaneously (25-200 micromol/L; IC50, 24 micromol/L), or 30 minutes (200 micromol/L) after PN exposure. Mesalamine protected the epithelial barrier function of T84 cells against PN. Mesalamine rapidly degraded PN, whereas the half-life of NO was not affected.
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Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce.
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Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients.