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Summary. Ischaemic colitis is known to be a severe emergency complication of interferon (IFN) therapy. However, as ischaemic colitis is an infrequent complication of IFN therapy, limited information is available regarding the safety of resuming IFN therapy after resolution of ischaemic colitis and subsequent recurrence. Here, we report two cases of ischaemic colitis during IFN therapy for chronic hepatitis C. Ischaemic colitis was fully healed within 1 week after its onset and IFN withdrawal, and IFN therapy was resumed following patients' wishes to do so. Ischaemic colitis did not recur after the resumption of IFN therapy, and sustained virological response was achieved in both patients. In this report, we also summarize the findings of 11 cases of IFN-associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Background Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. Aim To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. Methods Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 μg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. Results Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. Conclusion Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background and aim: SAMP1/Yit mice spontaneously develops intestinal inflammation. Previously, we demonstrated that the signal transducer and activator of transcription (STAT)-3/suppressor of cytokine signalling (SOCS)-3 pathway is pivotal in human inflammatory bowel disease. In our studies in SAMP1/Yit mice, the aim was to investigate whether STAT3 activation contributes to ileitis and to examine the therapeutic effects of this signal blockade. Methods: Intestinal expression of phospho-STAT3 in SAMP1/Yit mice and control AKR/J mice was examined by western blotting and immunohistochemistry. SOCS3 and interleukin 6 (IL-6) mRNA were determined by northern blotting and reverse transcription-polymerase chain reaction, respectively. We also examined the effects of intravenously injected hyper-IL-6, an IL-6/soluble IL-6 receptor fusion protein, and of soluble gpl 30-Fc, a specific inhibitor of soluble IL-6 receptor signalling, on STAT3 phosphorylation and disease severity in SAMP1/Yit mice. Results: Phospho-STAT3 was expressed strongly during the disease course in SAMP1/Yit mice but only transiently in AKR/J mice. Phospho-STAT3 was localised to epithelial and mononuclear cells in the diseased intestine of SAMP1/Yit mice. SOCS3 as well as IL-6 mRNAs were expressed in affected intestine. Administration of hyper-IL-6 caused disease exacerbation and enhancement of STAT3 phosphorylation. In contrast, soluble gp130-Fc administration ameliorated the disease and suppressed STAT3 phosphorylation. Conclusion: STAT3 signalling is critical in the development of intestinal inflammation in SAMP1 /Yit mice. Blockade of this signalling pathway by soluble gp130-Fc may have therapeutic effects in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

The presence and the role of soluble gp130, the soluble form of a component of the interleukin (IL)-6 receptor complex, were investigated in inflammatory bowel disease. The serum concentrations of soluble gp130 were increased in ulcerative colitis (active disease, median, 93·5 ng/ml; interquartile range, 26–125 ng/ml; inactive disease, 81 ng/ml, 24·8–137·3 ng/ml) and to a lesser extent in Crohn's disease (active disease, 66 ng/ml, 44·4–87·6 ng/ml; inactive disease, 63 ng/ml, 43·5–82·5 ng/ml) compared to normal controls (43 ng/ml, 27–59 ng/ml). Paired analysis of serum samples showed a decrease of IL-6 and soluble IL-6 receptor concentrations in both diseases and an increase of soluble gp130 concentrations, especially in ulcerative colitis, just after the resolution of disease exacerbation. Size fractionation of the serum revealed that a part of the IL-6 co-eluted with soluble gp130 and soluble IL-6 receptor. The IL-6-induced proliferation of murine B9 hybridoma was enhanced by recombinant soluble IL-6 receptor, whereas the proliferation was inhibited by recombinant soluble gp130. These results indicate that soluble gp130 may function as a natural inhibitor of the IL-6 actions in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal kinase (JNK) participates in intracellular signalling cascades that mediate inflammatory responses. Therefore, the JNK signalling may be involved in gastric injury and inhibition of this pathway may form the basis of a new strategy for the treatment of gastric injury. The aim of this study was to determine whether JNK participates in the formation of gastric lesions in an experimental model. Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. The amount of phospho-JNK in the rat stomach was determined using immunohistochemistry and Western analysis. Animals received subcutaneous injections of a specific JNK inhibitor SP600125 or vehicle and the extent of mucosal damage in the stomach was determined. Western analysis revealed early phosphorylation of JNK and, to a lesser extent, p38 as well as late phosphorylation of the p42/44 extracellular signal-related kinases during the development of gastric lesions. JNK was phosphorylated in epithelial cells and in occasional mononuclear cells present at lesion sites. These cells were rarely found in samples from control specimens. Treatment with SP600125 significantly reduced the extent of gastric lesions. These findings indicate that experimental gastric injury is associated with activation of the JNK signalling pathway, and also suggest that JNK inhibitors may play a role in the treatment of gastric injury in humans. [ABSTRACT FROM AUTHOR]

The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6-dependent immune processes observed in inflammatory bowel disease. [ABSTRACT FROM PUBLISHER]

IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001). In patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.01; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1β (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF-α) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-α in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Microscopic examination of a sigmoid colon biopsy specimen from the patient revealed cryptitis and inflammatory cells in the lamina propria; we also observed apoptotic cells (Fig.). GLO:EUW/01jan20:jgh14742-fig-0002.jpg PHOTO (COLOR): 2 Microscopic examination of a sigmoid colon biopsy specimen revealed cryptitis, inflammatory cells in the lamina propria, and apoptotic cells (arrow). gl. [Extracted from the article]

The purpose of this in vitro study was to evaluate the accuracy of reproducing color gradation for ceramic restorations using a spectrophotometer and a prototype computer program. Ten shade tabs from the Vitapan 3D Master shade guides were selected and measured at 4 regions from cervical to incisal. For each shade tab measured, 3 tooth shape ceramic specimens were fabricated. The color of the 10 shade tabs and their corresponding 3 tooth shape ceramic specimens were then measured in 10 incremental areas from gingival to incisal. The color differences between the shade tabs and their corresponding ceramic specimens were calculated. The color differences were then analyzed using Repeated Measured ANOVA. Three prosthodontists visually assessed the clinical acceptability of the corresponding ceramic specimens to the matched shade tabs. The mean color differences were clinically acceptable (below 3.6 îï) for incremental areas from 3 to 10, but not clinically acceptable for areas 1 and 2 (gingival area). The visual assessment resulted in all fabricated samples having a clinically acceptable color match to their corresponding shade tab. [ABSTRACT FROM AUTHOR]