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Among the frequencies of ecNOS intron 4 gene polymorphism, a allele displayed a significantly higher frequency in cases with end-stage renal failure (ESRF) not caused by diabetic nephropathy. ecNOS gene polymorphism in intron 4 appears, therefore, to affect the progression of renal failure in non- diabetic renal diseases, but the same conclusion could not be drawn in diabetic nephropathy.

These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Oxidative stress during ischemia-reperfusion acute renal failure (IR-ARF) was noninvasively evaluated with in vivo electron paramagnetic resonance (EPR) imaging. Female ICR mice underwent left nephrectomy and 30-min ischemia-reperfusion of the right kidney. Oxidative stress was evaluated as organ reducing activity with the half-lives of the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) using 1) conventional L-band EPR, which showed organ-reducing activity in the whole abdominal area; and 2) EPR imaging, which showed semiquantitative but organ-specific reducing activity. The results were compared with the reducing activity of organ homogenate and phosphatidylcholine hydroperoxide (PC-OOH) concentrations. Half-lives of carbamoyl-PROXYL in the whole upper abdominal area, measured by L-band EPR, were prolonged on day 3 after ischemia-reperfusion and recovered to the level of nontreated mice on day 7. This trend resembled closely that of serum creatinine and blood urea nitrogen concentration. The EPR imaging-measured carbamoyl-PROXYL half-life was also prolonged on day 3 in both the kidney and the liver. However, in the kidney this showed only partial recovery on day 7. In the liver, this convalescence was more remarkable. The ex vivo studies of organ reducing activity and PC-OOH agreed with the results from EPRI, but not with those from L-band EPR. These results indicate that renal reducing activity shows only partial recovery on day 7 after ischemia-reperfusion, when serum creatinine and blood urea nitrogen have recovered. EPR imaging is an appropriate and useful method for the noninvasive evaluation of oxidative stress in the presence of renal injury.

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To clarify the organ in which methylguanidine is synthesized, high doses of creatinine, which is known to stimulate the synthesis of methylguanidine, were administered to male Wistar rats intraperitoneally. Various tissues of the rats were frozen by a freeze clamp method before and 1, 2 and 3 h after injection, and methylguanidine was determined by high-pressure liquid chromatography using 9,10-phenanthrenequinone for fluorometric determination. We found evidence that the liver, kidney, lung, muscle, red blood cells and gut flora synthesize methylguanidine. In addition, we measured the synthesis of methylguanidine in isolated hepatocytes prepared from normal rats following the addition of creatinine, arginine and guanidinoacetic acid to the incubation medium. Synthesis of methylguanidine was observed only in those incubations which contained creatinine, and was dependent on the concentration of creatinine in the media and on the incubation period. Isolated rat hepatocytes also synthesized guanidine in the presence of guanidinoacetic acid. These results indicate that the liver is one of the organs which synthesize methylguanidine and also that creatinine is the precursor.