Fecal calprotectin is a clinically relevant biomarker of mucosal healing in patients with quiescent ulcerative colitis.

BACKGROUND AND AIM: Calprotectin is an abundant protein in neutrophils, which infiltrate the mucosa during inflammation. Fecal calprotectin (FC) level has shown correlation with disease activity in ulcerative colitis (UC) patients. Additionally, FC level is expected to indicate mucosal healing (MH). This study was to see the significance of FC for predicting MH in patients with quiescent UC. METHODS: A total of 112 patients with quiescent UC were included. After taking blood and stool samples, patients underwent total colonoscopy, and the Mayo endoscopic subscore was recorded. FC was measured by fluorescence enzyme immunoassay. C-reactive protein, hemoglobin, erythrocyte sedimentation rate, and serum albumin were measured as conventional biomarkers. MH was defined as Mayo 0 or 0 and 1, and receiver-operator characteristic analyses were undertaken to determine the significance levels of measurements. RESULTS: Data from 105 patients were available. Eleven patients showed Mayo ≥ 2. The median (interquartile range) of FC level of all patients was 115 µg/g (45.4-420). The area under the curve (AUC) in receiver operator characteristic analysis of FC to predict Mayo 0 and 1 was 0.869 with a cut-off value of 200 µg/g yielding 67% sensitivity and 91% specificity, which were the best among all biomarkers. However, the power of FC to predict Mayo 0 was modest; the AUC was 0.639 and cut-off value 194 µg/g with 71% sensitivity and 58% specificity. CONCLUSIONS: Based on the findings of this study, we believe that FC is a clinically relevant biomarker of MH in patients with quiescent UC. Other favorable features of FC test include feasibility and non-invasiveness.

Effects of Dietary Plant-Origin Glucosylceramide on Bowel Inflammation in DSS-Treated Mice.

The effects of dietary plant-origin glucosylceramide (GlcCer) on symptoms similar to those of inflammatory bowel diseasewere investigated in dextran sulfate sodium salt (DSS)-treated mice. Dietary GlcCer suppressed decreases in body weight due to DSS administration. To determine its effects on the colon, we examined its surface under a microscope following toluidine blue staining. Dietary GlcCer decreased DSS-induced chorionic crypt injury and elevated myeloperoxidase levels. Moreover, dietary GlcCer significantly suppressed the production of cytokines by the intestinal mucosa. These results provide evidence for the suppression of DSS-induced inflammation by dietary GlcCer.

A case of Degos disease: demonstration of C5b-9-mediated vascular injury.

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.

The Effect of Oral Intake of Low-Temperature-Processed Whey Protein Concentrate on Colitis and Gene Expression Profiles in Mice.

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology and can lead to inflammation and cancer. Whey proteins contain many bioactive peptides with potential health benefits against IBD. We investigated the effect of low-temperature-processed whey protein concentrate (LWPC) on the suppression of IBD by using a dextran sodium sulfate (DSS)-induced colitis model in BALB/c mice. Oral intake of LWPC resulted in improved recovery of body weight in mice. Histological analysis showed that the epithelium cells of LWPC-treated mice were healthier and that lymphocyte infiltration was reduced. The increase in mucin due to the LWPC also reflected reduced inflammation in the colon. Transcriptome analysis of the colon by DNA microarrays revealed marked downregulation of genes related to immune responses in LWPC-fed mice. In particular, the expression of interferon gamma receptor 2 (Ifngr2) and guanylate-binding proteins (GBPs) was increased by DSS treatment and decreased in LWPC-fed mice. These findings suggest that LWPCs suppress DSS-induced inflammation in the colon by suppressing the signaling of these cytokines. Our findings suggest that LWPCs would be an effective food resource for suppressing IBD symptoms.

Elevation of carcinoembryonic antigen coinciding with disease activity of ulcerative colitis.

We report on three cases of ulcerative colitis who presented with increased levels of serum carcinoembryonic antigen (CEA) during the active stage. All cases were pancolitis with a moderate to severe disease course. After remission induction with medical therapies, serum CEA levels decreased to the normal reference range. Immunohistochemical analyses demonstrated the existence of CEA not only along with the apical surface of the colonic epithelia but also at the cytosol of the inflamed epithelia where goblet cells were depleted during the active stage. We speculate that CEA was up-regulated by inflammatory response particularly in the process of epithelial regeneration.

The impact of disease activity of Crohn's disease during pregnancy on fetal growth.

Although it is known that women with inflammatory bowel disease have an increased risk of adverse outcome of pregnancy, the relationship between disease activity during pregnancy and the adverse outcome is not well known. A 29-year-old woman with Crohn's disease presented with flare-up at the end of the first trimester. Although the disease had been rendered inactive by maintenance infusion of infliximab, the drug was discontinued at the time of conception because of the patient's fear of the adverse effects of infliximab. Because retardation of fetal growth was observed at the flare-up, we re-started infliximab therapy. As disease activity reduced with therapy, the retardation of fetal growth subsequently improved. The patient finally delivered a newborn of 2550 g in weight and no adverse outcome was noted. The case supports the notion that disease activity is a risk factor for adverse outcome in pregnancy and that infliximab may be safely used in pregnancy.

Prokinetics influence the pharmacokinetics of rabeprazole.

BACKGROUND: Proton pump inhibitors (PPIs) are unstable at a low PH. Accelerated transfer of PPIs to the upper small intestine may influence the pharmacokinetics of PPIs. AIM: To see if concomitant use of mosapride citrate with rabeprazole sodium influences the pharmacokinetics of the PPI. METHODS: Two-way crossover pharmacokinetic studies were conducted in 9 healthy subjects. 20 mg of rabeprazole was given orally and plasma was obtained before and 1, 2, 3, 4, 5, 6 and 8 h after the dosing. Two weeks later, 5 mg of mosapride was given concomitantly with rabeprazole and plasma was collected as above. The plasma concentrations of rabeprazole were determined by high-performance liquid chromatography. The maximum plasma concentrations (C(max)) and the area under the time-plasma concentration curve (AUC) of rabeprazole, and the time to maximum plasma concentration (t(max)) were compared in the presence or absence of mosapride. RESULTS: Concomitant use of mosapride resulted in significant increases of mean C(max) and mean AUC with ratios of 1.57 and 1.47, respectively. The median t(max) changed from 4 to 3 h, although the change was not significant. CONCLUSIONS: Mosapride significantly influenced pharmacokinetics of rabeprazole. Co-administration of mosapride could have some favorable effect in PPIs-based therapy.