Ultrastructure of glomerular basement membrane by quick-freeze and deep-etch methods

Ultrastructure of glomerular basement membrane by quick-freeze and deep-etch methods. The glomerular basement membrane of rat kidneys were three-dimensionally observed by quick-freeze and deep-etch replica methods at high resolution. The middle layer (lamina densa) was composed of 6 to 10nm fibrils which formed a meshwork structure. The space between the fibrils had polygonal shape. The average long dimension of the space between fibrils was 17nm and the short one was 13nm. At the outer layer (lamina rara externa), fibrils connected podocytes perpendicularly with the meshwork of the middle layer. At the inner layer (lamina rara interna), similar perpendicular fibrils also connected endothelial cells with the meshwork of the middle layer. This is the first report to visualize the three-dimensional meshwork structure of the middle layer (the lamina densa) in situ. The function of anchoring podocytes to the lamina densa was suggested in the perpendicularly arranged fibrils of the outer layer. The quick-freeze and deep-etch method is useful in analyzing filamentous ultrastructure in glomeruli, and will be applied to clarifying pathological ultrastructure in kidney diseases

PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling

The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor α (PPARα), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARα in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARα resulted in high susceptibility to glomerulonephritis. To investigate whether PPARα activation improves the disease activity of MsPGN, we examined the protective effects of a PPARα agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARα, which outweighed the PPARα deterioration associated with the nephritic process. The PPARα activation appeared to suppress the NF-κB signaling pathway in glomeruli by the induction of IκBα, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARα-related medicines against MsPGN. PPARα-related medicines might be useful as a treatment option for CKD

Kidney dysfunction induced by protein overload nephropathy reduces serum sulfatide levels in mice

We recently proposed serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure (ESRF), based on the possible antithrombotic properties of this molecule. In this earlier study, the level of serum sulfatides was gradually decreased in parallel with kidney dysfunction; however the precise mechanism underlying this decrease was unknown. The aim of the present study was to investigate the mechanism underlying the decrease in serum sulfatide levels caused by kidney dysfunction in an experimental animal model. To produce a kidney dysfunction animal model, we prepared a mouse model of protein overload nephropathy. Using high-throughput analysis combined with matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, we measured the levels of sulfatides in the sera, livers, small intestines and kidneys of protein overload nephropathy mice. As the disease progressed, the levels of sulfatides in sera decreased. Also, the levels in livers and small intestines decreased in a similar manner to those in sera, to approximately 60% of the original levels. On the contrary, those in kidneys increased by approximately 1.4-fold. Our results indicate that kidney dysfunction affects the levels of sulfatides in lipoprotein-producing organs, such as livers and small intestines, and lowers the levels of sulfatides in sera.ArticleNEPHROLOGY. 14(7):658-662 (2009)journal articl

反復性女子膀胱炎患者に認められた膀胱三角部の扁平上皮化生について

膀胱鏡に膀胱三角部に白斑を示した44例の反復性膀胱炎の女子の同部生検をおこない検討した.組織学的に白斑部の上皮はさまざまなGradeの扁平上皮化生を示し, 粘膜下は線維下傾向を示したが, その傾向は, 頻回な膀胱炎症状既往を有する例ほど著しかった.軽～中等度の扁平上皮化生を示した群では尿道部細菌を認めたが, 重症な扁平上皮化生を示した群ではそれを認めなかった.以上よりみて, 尿道部細菌は扁平上皮化生の発生や初期の進展のひとつの要因と見做しうるが, 一層進展した上皮化生は, 同部細菌とは無関係に, 単に頻回な症状のくり返しのみで生じうることが推測されたUrocystic mucosal biopsies of the white patch on the trigone in 44 women complaining of dysuria and frequency with or without bacteriuria showed varying degrees of squamous metaplasia as well as submucosal fibrosis. The patients with more frequent episodes of such symptoms in the past had more severe squamous metaplasia with submucosal fibrosis. Introital bacteria were found in almost all patients with mild or moderate development of squamous metaplasia, but not in those with severe lesions. These facts suggest that introital bacteria may be one of the causative factors for the initiation and early development of these abnormal mucosal changes. However, the further progression to severe mucosal alteration seems to be independent of any bacteria and this severe mucosal alteration may result in recurrence of such symptoms

(Studi Toksisitas Akut dan Subakut dari Ekstrak Minyak Buah Merah pada Tikus Sprague Dawley)

Pandanus conoideus is exclusively grown in Papua island and its neighbor areas and its fruit (buah merah) has been utilized as food supplement by the native Papua people for a long period. recently it was found that its extract oil (SMB) contains contents of carotenoids ,especially a novel micronutrient beta-cryptoxanthin .we consider that SBM is a potent chemopreventive supplement against some types of cancer and provide health benefits for chronic diseases .in the present studies, we evaluated acute ad subacute toxicities of SBM using Sprague Dawley rats.Oral acute toxicity of SBM using female rats was not observed and LD 50 was more than 2 ml/kg in subacute toxicity study ,SMB was orally administered at 0.1,0.3 and 1.0 ml/kg to male and female rats for consecutive 4 weeks .no findings associated with SBM observed we consecutive 4 weeks .no findings associated with were observed we conclude that SBM is a safe food supplement