The reason for the heterogeneity in ARF associated with renal hypouricaemia remains unknown. Further studies, especially on molecular mechanisms, are required to establish the best guidance against ARF recurrence.

TNF-a inducing protein (Tipa) is secreted from Helicobacter pylori (H. pylori): it is a potent inducer of TNF-a and chemokine genes, mediated through NF-jB activation, and it also induces tumorpromoting activity in Bhas 42 cells. To investigate the carcinogenic mechanisms of H. pylori with Tipa, we first examined how Tipa acts on gastric epithelial cells. We found that fluorescent-Tipa specifically bound to, and then entered, the cells in a dose-and temperature-dependent manner, whereas deletion mutant of Tipa (del-Tipa), an inactive form, neither bound to nor entered the cells, suggesting the presence of a specific binding molecule. Mutagenesis analysis of Tipa revealed that a dimer formation of Tipa with a disulfide bond is required for both specific binding and induction of TNF-a gene expression. A confocal laser scanning microscope revealed some Tipa in the nuclei, but del-Tipa was not present, which indicated that an active form of Tipa can penetrate the nucleus and may be involved in the induction of TNF-a gene expression. Examination of Tipa production and secretion in 28 clinical isolates revealed that H. pylori obtained from gastric cancer patients secreted Tipa in significantly higher amounts than did H. pylori from patients with chronic gastritis, suggesting that Tipa is an essential factor in H. pylori inflammation and cancer microenvironment in the human stomach. Tipa is thus a new carcinogenic factor of H. pylori that can enter the nucleus through a specific binding molecule, and its mechanism of action is completely different from that of CagA.

Background: Glucose polymer is an active osmotic agent that is increasingly used as an alternative to glucose in peritoneal dialysis fluids. It was recently reported that the duration of peritoneal dialysis can be extended by using glucose polymer in patients with poor ultrafiltration. We previously demonstrated that high glucose levels damage the intercellular junctions of cultured human peritoneal mesothelial cells (HPMC), but little is known about the influence of glucose polymer. Therefore, we investigated the effects of glucose polymer on the intercellular junctions of HPMC. Methods: HPMC were isolated, cultured, and identified according to the modified method of Stylianou. M199 medium was supplemented with peritoneal dialysis solutions containing 7.5% glucose polymer or 1.5, 2.5, and 4.25% glucose. After 6 h, cell viability was assessed, intercellular junction proteins were examined by immunofluorescence techniques, and the concentration of transforming growth factor-β1 in the culture supernatant was determined. Results: Glucose significantly suppressed cell viability and significantly increased transforming growth factor-β1 production when compared with control or glucose polymer cultures. Peritoneal dialysis solutions containing 4.25% glucose caused the detachment of HPMC. Immunofluorescence of intercellular junction proteins (tight junctions: ZO-1, occludin, and claudin-1; adherens junctions: β-catenin) became weak and uneven after culture with glucose. On the other hand, glucose polymer caused little change in the immunofluorescence of these proteins when compared with control cultures. Conclusions: Glucose polymer seems to be less toxic to HPMC than glucose itself, suggesting that the glucose polymer may be better for peritoneal dialysis.

These results indicate the potential importance of ERK1/2 and p38 MAPK signaling pathways in Ang II-induced fibronectin expression in HPMC, and suggest the therapeutic potential of AT1 receptor blockers in the prevention or treatment of peritoneal fibrosis in patients on peritoneal dialysis.