[Acute hepatitis C infection with prolonged intrahepatic cholestasis and remarkable progression of fibrosis mimicking fibrosing cholestatic hepatitis].

We report the case of a 71-year-old woman with acute hepatitis C infection and persistent viremia since 2 years. Her clinical course was characterized by general fatigue and prolonged jaundice with unusually high serum bilirubin levels. Liver histology showed lymphocyte infiltration, marked fibrosis, and severe cholestasis in the periportal zone, findings mimicking fibrosing cholestatic hepatitis (FCH). Fibrosing cholestatic hepatitis is a life-threatening form of recurrent hepatitis C infection that typically occurs in immunosuppressed patients. Here we report the rare case of an immunocompetent patient who developed this condition.

Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors.

INTRODUCTION: Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. METHODS: The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. RESULTS: Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. CONCLUSION: The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.

Comparison of patient acceptance of sodium phosphate versus polyethylene glycol plus sodium picosulfate for colon cleansing in Japanese.

BACKGROUND AND AIM: In Japan, patient acceptance of bowel preparation methods before colonoscopy remains unknown. This study was conducted to evaluate the patient acceptance of sodium phosphate (NaP) tablets and polyethylene glycol solution (PEG) with sodium picosulfate. METHODS: One hundred patients were randomized into one of the following two groups: the NaP tablet first-use group or the PEG with sodium picosulfate first-use group in a crossover design trial. Patient acceptance and incidence of adverse events were evaluated using a questionnaire. Colon-cleansing effectiveness was also evaluated. RESULTS: Patients' overall impressions of the preparations were significantly different between the NaP tablet (77.9%, 67/86) and PEG with sodium picosulfate (60.5%, 52/86; P = 0.001). Nausea incidence as an adverse event was significantly different between the two regimens (P = 0.03). Colon-cleansing effectiveness was not significantly different between the two regimens. CONCLUSIONS: The results of this crossover study showed that patient acceptance was similar to those previously reported in a parallel-group comparison. In Japanese patients, preference for and acceptance of NaP tablets was significantly higher than that for PEG with sodium picosulfate solution.

Significant role of ceramide pathway in experimental gastric ulcer formation in rats.

Ceramides have emerged as key participants in the signaling pathway of cytokines and apoptosis. We previously revealed that phorbol 12-myristate 13-acetate (PMA) induced experimental ulcers in rat gastric mucosa. In this study, we investigated the role of ceramide in ulcer formation and its relation to the activation of transcription factors and apoptosis. PMA was subserosally injected to rat glandular stomach. Fumonisin B1 (FB1), an inhibitor of ceramide synthase, was administered together with the PMA. The time course of ceramide content was quantified using thin layer chromatography and the number of apoptotic cells was determined by immunohistochemistry. The activation of transcription factor nuclear factor-kappaB (NF-kappaB) or activator protein-1 (AP-1) was evaluated using an electrophoretic mobility shift assay. The administration of FB1 attenuated PMA-induced gastric ulcer formation in a dose-dependent manner. Before the ulcers became obvious, the ceramide content (C18 and C24 ceramide) increased significantly in the gastric wall. The activation of NF-kappaB and AP-1 and an increase in the number of apoptotic cells were also observed. Both of these were significantly inhibited by the coadministration of FB1. However, NF-kappaB inhibitors attenuated gastric ulcer formation without affecting the ceramide content or the number of apoptotic cells. Ceramide formation in the stomach significantly contributes to PMA-induced tissue damage, possibly via the activation of transcription factors and an increase in apoptosis in the gastric mucosa. However, after the increase in ceramide levels, the NF-kappaB and apoptosis pathways may be separately involved in ulcer formation.