Yasushi Utsunomiya

Suppressive Effect of Superoxide Dismutase on Adriamycin Nephropathy

A single intravenous injection of adriamycin (ADR) results in marked proteinuria and glomerular morphological changes that are similar to minimal-change disease in humans. We examined the effect of superoxide dismutase (SOD) on ADR-induced proteinuria. ADR in a dose of 7.5 mg/kg body weight significantly increased urinary protein by day 14; proteinuria rapidly increased thereafter. Concurrent administration of SOD (50 mg/kg) over 30 min prior to and 30 min following ADR injection markedly reduced proteinuria. Twenty-one days after the treatment with SOD, the amount of urinary protein was 108.6 +/- 43.1 mg/24 h in the experimental animals, while it was 221.6 +/- 102.9 mg/24 h in the ADR control group (p less than 0.05). There were also less severe glomerular morphologic changes in the SOD group versus ADR controls. The protective effects of SOD provide indirect evidence that oxygen free radicals are important mediators of ADR-induced proteinuria.

Immunohistochemical characterization of glomerular inflammatory cells and expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses

According to previous report, adhesion of CD8‐positive cells and macrophages to glomerular endotherial cells through the lymphocyte function‐associated antigen‐1 (LFA‐1)/intercellular adhesion molecule‐1 (ICAM‐1) pathway is crucial for the initiation and subsequent progression of anti‐glomerular basement membrane (anti‐GBM) antibody‐induced glomerulonephritis (anti‐GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA‐1/ICAM‐1 expression were examined in anti‐GBM nephritis induced in WKY rats with monoclonal anti‐GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8‐positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM‐1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA‐1‐positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti‐GBM nephritis.

Mizoribine oral pulse therapy for a patient with polyarticular juvenile idiopathic arthritis

Mizoribine (MZR) is a novel immunosuppressive agent developed in Japan. It has been used in patients with renal transplantation, lupus nephritis, nephrotic syndrome and rheumatoid arthritis. 1 There are several reports on the effi cacy of MZR in patients with juvenile idiopathic arthritis (JIA). However, the clinical application of MZR for JIA remains low compared with that of methotrexate (MTX) or other disease-modifying antirheumatic drugs. Recently, some studies have shown that MZR oral pulse therapy may be of benefi t to a proportion of patients with fl areup of lupus nephritis as an alternative to an increased dose of corticosteroids. 2 The authors speculated that the mild clinical effi cacy of MZR may be attributable to low peak blood levels and that oral pulse therapy may achieve a suffi ciently high peak blood concentration of MZR. The authors of the present report, therefore, attempted MZR oral pulse therapy for a patient with JIA, and assessed its effi cacy and safety.