Search

Hypertonic glucose in a peritoneal dialysate may modulate cell metabolism in the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). To examine the effects of high glucose concentration and hyperosmolarity, rat mesothelial cells were cultured for 3 or 6 days in media containing either 5, 25 or 50 mM glucose or 5 mM glucose containing 20 or 45 mM mannitol. Fibronectin gene expression was investigated by Northern blot analysis. By day 6, fibronectin mRNA levels increased compared to 5 mM glucose controls with increasing glucose concentration (25 mM, 193%; 50 mM, 314%); high osmolarity due to mannitol did not increase mRNA levels (20 mM and 45 mM mannitol yielded 75 and 104%, respectively). Thus, hypertonic glucose augments fibronectin gene expression in peritoneal mesothelial cells due to the higher concentrations of glucose and not to hyperosmolarity. This glucose-driven increase in fibronectin expression may contribute to the peritoneal fibrosis in CAPD patients.

Memory T cells respond in several functionally different ways from naive T cells and thus function as efficient effector cells. In this study we showed that primed T cells were more resistant to Fas-mediated activation-induced cell death (AICD) than naive T cells using OVA-specific TCR transgenic DO10 mice and Fas-deficient DO10 lpr/lpr mice. We found that apoptosis was efficiently induced in activated naive T cells at 48 and 72 h after Ag restimulation (OVA peptide; 0.3 and 3 μM), whereas apoptosis was not significantly increased in activated primed T cells at 24–72 h after Ag restimulation. We further showed that the resistance to AICD in primed T cells was due to the decreased sensitivity to apoptosis induced by Fas-mediated signals, but TCR-mediated signaling equally activated both naive and primed T cells to induce Fas and Fas ligand expressions. Furthermore, we demonstrated that primed T cells expressed higher levels of Fas-associated death domain-like IL-1β-converting enzyme inhibitory protein (FLIP), an inhibitor of Fas-mediated apoptosis, at 24–48 h after Ag restimulation than naive T cells. In addition, Bcl-2 expression was equally observed between activated naive and primed T cells after Ag restimulation. Thus, these results indicate that naive T cells are sensitive to Fas-mediated AICD and are easily deleted by Ag restimulation, while primed/memory T cells express higher levels of FLIP after Ag restimulation, are resistant to Fas-mediated AICD, and thus function as efficient effector cells for a longer period.

Excess protein intake enhances the progression of renal failure. The oral carbonaceous adsorbent, AST-120, was found experimentally and clinically to retard the progression of renal failure. This study was designed to determine whether deterioration of renal function by dietary protein loading can be prevented or mitigated by this oral adsorbent. Rats with uremia induced by partial renal infarction were fed a normal or high-protein diet for 70 days with or without AST-120, in which the inorganic phosphate content was adjusted to the same level. The survival rate deteriorated with the high dietary protein, but was improved from 30% to 100% with AST-120. Dietary protein loading reduced renal function, based on creatinine clearance. AST-120 improved renal function and renal histopathology not only in the normal diet group but in the high-protein group as well. The progression of renal failure induced by protein loading is thus shown to be prevented by oral AST-120. The mechanism for its action remains to be clarified.