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

Risk for atrial fibrillation in patients with hypertrophic cardiomyopathy: Association with insulin resistance

SummaryBackgroundWe undertook a cross-sectional study to test the hypothesis that patients with hypertrophic cardiomyopathy (HCM) who have impaired left ventricular (LV) diastolic function are insulin resistant. We also evaluated the relation between the development of atrial fibrillation (AF) and insulin resistance (IR) in patients with HCM.Methods and resultsEighty-eight patients with HCM (71 men, 17 women) were enrolled in the study. IR was estimated using the homeostasis model assessment (HOMA) index. Echocardiographically determined left atrial (LA) dimension was measured as a marker of LA size. The ratio of trasmitral early LV filling velocity to early diastolic mitral annulus velocity (E/e′) was also measured as a marker of LV diastolic function. Twenty-seven patients (31%) had IR. Multivariate logistic regression analyses showed that independent determinants of AF were increased LA size [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.2–9.8] and impaired LV diastolic function [OR 4.6, 95% CI 1.6–12.8]. The strongest determinant of LA size was the HOMA index (p=0.0005). Similarly, the HOMA index (p=0.0019) was an independent determinant of LV diastolic function.ConclusionIR is highly prevalent among non-diabetic patients with HCM. A possible mechanism by which IR affects the development of AF is mediated through its association with increased LA size or impaired LV diastolic function. IR may be an important underlying mechanism for the genesis of AF in HCM

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

EVALUATION OF SOCIAL ENVIRONMENTAL EFFICIENCY ON RECYCLING OF CONSTRUCTION SLUDGES AS GROUND MATERIALS

我が国では環境意識の高まりから廃棄物リサイクルが推進されているものの，リサイクルにはコストを要するため，その市場性が問われている．一方，廃棄物リサイクルを実施する本質は環境負荷の削減である．本研究では直接コストに加え，環境負荷を環境コストとして内部化することで，廃棄物リサイクルを社会的に評価する社会環境効率性評価手法を検討・試作する．具体的に，廃棄物リサイクルには様々な不確実要素が絡み合っているため，感度分析およびモンテカルロシミュレーションを用いることで不確実性をも考慮した社会環境効率性評価を実施した．その結果，特に再資源化等率の低い建設汚泥に着目したところ，建設汚泥のリサイクルの社会環境的な有意性を定量的に評価することができた

Experimental study on properties of liquefied stabilized soil produced with different types of solidifiers and thickeners

Liquefied soil stabilization methods have been applied in a wide range of construction projects especially in Japan for the effective geotechnical reuse of construction-generated soil. However, after the placement of the liquefied stabilized soil is complete, water often rises to the surface and causes the bleeding phenomenon. Chromium oxide, which is produced in the manufacturing process of iron ore and steel scrap, is sometimes added to the cement solidifier (OPC solidifier) that is mixed into the liquefied stabilized soil. The environmental conditions under which the cement solidifier and construction-generated soil encounter each other change the transformation of the chromium oxides, i.e., they leach as hexavalent chromium. Hexavalent chromium is more likely to be leached when the pH is low or the moisture content is high. These are some of the environmental issues related to the application of liquefied stabilized soil. In this study, the addition of a thickener for liquefied stabilized soil is proposed; it is used to prevent segregation while maintaining fluidity. Specifically, the authors conduct various laboratory experiments, and then perform several physical analyses using the specimens after the experiments to investigate how the addition of the thickener has changed the properties of the liquefied stabilized soil. The authors also examine the properties of each type of liquefied stabilized soil by comparing it to normal liquefied stabilized soil when the amount of OPC solidifier in the liquefied stabilized soil is reduced, and instead, a solidifier mixing with waste glass powder and blast furnace slag is used to make the liquefied stabilized soil