Despite intensive treatment, steroid-resistant nephrotic syndrome (NS) often progresses to endstage renal disease. Therefore, a more accurate and quick histological diagnosis is required to properly treat such patients. The aim of this study was to introduce a novel approach to the histological diagnosis of pediatric NS by low vacuum scanning electron microscopy (LVSEM) and to describe the morphological differences in glomeruli between steroid-sensitive and steroid-resistant NS specimens. The subjects were three patients with steroid-sensitive NS and four patients with steroid-resistant NS. Conventional renal biopsy paraffin sections were stained with platinum-blue (Pt-blue) or periodic acid methenamine silver (PAM) and directly observed under LVSEM at magnifications between ×50 and ×10,000. The Pt-blue-stained sections showed three-dimensional structural alterations in glomerular podocytes and foot processes. PAM-stained sections showed changes in the structure and thickness of the glomerular basement membrane (GBM). Consequently, many round-shaped podocytes and elongated primary foot processes were exclusively recognized in steroid-resistant NS, although irregularities in foot process interdigitation, fusions, effacements, and microvillus transformations were observed in both steroid-sensitive and steroidresistant NS. Irregularities in thickness and the wrinkling of GBMs were clearly detected in steroid-resistant NS. The evaluation by LVSEM is probably useful for the renal histological diagnosis of pediatric NS.Nephrotic syndrome (NS) comprises proteinuria, hypoalbuminemia, hypercholesterolemia, and edema. Pediatric patients with NS are usually treated with corticosteroids (13). Patients who respond to steroids (steroid-sensitive NS) have good clinical outcomes, whereas patients who do not respond to steroids (steroid-resistant NS) are predisposed to the development of end-stage renal disease. Histopathologically, most pediatric patients with steroid-sensitive NS show minor glomerular abnormalities, and patients with steroid-resistant NS generally have focal segmental glomerulosclerosis (FSGS) (25). Under light microscopy (LM), minor glomerular abnormalities are defined as a slight or no increase in the mesangial matrix or cellularity without focal segmental glomerular collapse, scarring, endocapillary proliferation, or adhesions. FSGS shows focal and segmental glomerular collapse, scarring, endocapillary proliferation, or adhesions of glomeruli with minimal abnormalities (21). However, it is not clear whether the glomeruli with no obvious changes in FSGS are different from those in minor glomerular abnormalities. In addition, it is difficult to diagnose FSGS when the NS biopsy section does not include glomeruli with the typical alterations of FSGS described above, although the differential diagnosis between minor glomerular abnormalities and FSGS is very
We studied the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
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