Lipid peroxidation may be involved in the pathogenesis of focal segmental glomerulosclerosis (FSGS). In the present study we examined whether lipid-soluble antioxidants, probucol and vitamin E, could inhibit renal injury in rats with chronic puromycin aminonucleoside (PA) nephrosis and dietary hypercholesterolemia by protecting lipoproteins from oxidation. Male Sprague-Dawley rats received six intraperitoneal injections of PA over a 10 week period and were fed a high cholesterol (HC) diet (PA-HC) or the same diet supplemented with either 1% probucol or vitamin E (100 IU/kg) for 32 weeks. For comparison, a group of rats received PA injections and a normal diet (PA-normal) with or without probucol or vitamin E. Another group rats received saline injections instead of PA and were fed a HC diet (Sal-HC) with or without probucol or vitamin E. At the end of the experiment, proteinuria, FSGS and tubulointerstitial lesions were present in the untreated rats with PA-HC or PA-normal. The magnitude of these lesions was significantly greater in the PA-HC rats than the PA-normal. In contrast to the PA-HC group with hypercholesterolemia, the PA-normal group did not show hypercholesterolemia from week 16 onwards. The rats with PA-HC alone showed significantly higher renal cortical malondialdehyde (MDA) levels and greater susceptibility of plasma very low density lipoprotein (VLDL) + low density lipoprotein (LDL) to the copper-mediated oxidation than the rats with PA-normal or Sal-HC alone. The administration of probucol or vitamin E in the rats with PA-HC significantly reduced the susceptibility of plasma VLDL + LDL to in vitro oxidation, renal cortical MDA level, proteinuria, mesangial volume density and magnitude of FSGS and interstitial lesions. Immunohistochemical staining of renal tissue showed focal segmental distribution of oxidized LDL (Ox-LDL) in the glomeruli of rats with PA-HC. Administration of probucol or vitamin E reduced the intensity of Ox-LDL staining. The staining with ED1 demonstrated that infiltrating glomerular macrophages were significantly more prevalent in the untreated rats with PA-HC than PA-normal or Sal-HC. Treatment with probucol or vitamin E significantly reduced the number of glomerular macrophages in the rats with PA-HC. These results suggest that alimentary hypercholesterolemia aggravates the renal damage in association with increased renal lipid peroxides in chronic PA nephrosis, and that dietary probucol or vitamin E attenuates renal injury in rats with PA-HC possibly by making lipoproteins resistant to oxidation and by inhibiting intraglomerular macrophage infiltration.
In membranous nephropathy (MN), the glomerular basement membrane (GBM) is thickened due to accumulation of GBM material between and around the subepithelial immune deposits. Alterations in the GBM components in relation to subepithelial deposits and GBM thickening are not clearly defined. The GBM distribution of classical and novel [α4(IV)] chains of type IV collagen, laminin, and fibronectin have been studied in seven patients with MN and in three normal controls by a quantitative immunogold technique. In normal kidneys, the labelling of type IV collagen or fibronectin was distributed predominantly along the endothelial side of the GBM; α4(IV) was found in the lamina densa; and laminin was concentrated in the epithelial zone of the GBM (P<0·01). In MN, there were increased immunogold densities for classical and novel type IV collagen chains, laminin, and fibronectin in the spikes of MN patients compared with controls (P<0·05). Furthermore, gold particle labelling for the α4(IV) collagen chain was increased in the middle zone (P<0·01) and that for fibronectin was increased in the endothelial and middle zones of the GBM (P<0·05) compared with normal controls. These findings suggest that subepithelial immune deposits stimulate glomerular epithelial cells (GEC), resulting in enhanced secretion of classical and novel type IV collagen chains, laminin, and fibronectin, forming spikes in MN; of these newly formed components, only novel type IV collagen appears to migrate towards the middle zone of the GBM, contributing to thickening of this zone. The results also suggest that fibronectin, possibly derived from the circulation, is related to thickening of the endothelial zone of the GBM, which in turn might be related to progressive glomerulosclerosis. © 1997 by John Wiley & Sons, Ltd.
The objectives of the study were to introduce and investigate the reliability of a new flap for postauricular defects using the retroauricular artery perforator.Twenty auricles from 10 Asian human cadavers were dissected to examine the retroauricular perforator distribution and diameter. Fourteen patients with postauricular defects underwent reconstruction using the retroauricular artery perforator from 2013 to 2015. After locating the position of the perforator by ultrasound Doppler blood flow detection, a suitable flap was designed according to the defect's size, condition, and distance from the pedicle. The flap was meticulously elevated, rotated appropriately, and sutured to the defect. The donor site was then closed.Cadaver dissection showed that the posterior auricular artery produces at least 2 constant branches with an external diameter of 0.84 ± 0.25 mm at the origin. These branches proceed toward the mastoid process at the height of the auriculocephalic angle to nourish the skin and fascia. A total of 14 clinical cases were available for 3 to 12 months postoperative follow-up. All flaps survived completely, maintaining good skin color, perfect outer contour, and complete patient satisfaction with the aesthetic results after initial treatment.Retroauricular artery perforator-based island flaps appear to be ideal for 1-stage reconstruction of postauricular skin defects.
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