成人発症の微小変化型ネフローゼ症候群に対するプレドニゾロン初期投与量と，寛解，再発，及び感染症との関連

Background: A dose of 0.5-1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD. Methods: We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics. Results: Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H. Conclusion: The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.博士（医学）・甲第803号・令和3年12月21日© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/

Measurement of phosphatidylcholine hydroperoxides in solution and in intact membranes by the ferric-xylenol orange assay

Formation of a colored complex between ferric iron and xylenol orange (XO) has been used for the determination of hydroperoxides (FOX method). Original or modified FOX methods were performed on aqueous or organic solutions consisting of a single phase. However, for lipid peroxides in heterogeneous samples, such as biological materials, much of the lipid is sequestered in a separate phase. Organic solvent extraction of these lipids is often incomplete and may result in additional peroxidation during the extraction procedure. In this study, we applied the FOX assay for measurement of the membrane phosphatidylcholine hydroperoxides (PC-OOH) in separated phases. The presence of membranous egg yolk phosphatidylcholine (EYPC) in 60% MeOH shifted the broad peak at 560 nm of Fe³⁺–XO complex to 610 nm with a sharp peak associated with the increased intensity of the absorbance. The shift of the peak is useful to measure the unknown amounts of Fe³⁺ because the uncomplexed XO considerably contributed to the absorbance of the peak at 560 nm but did not affect the absorbance at 610 nm. EYPC was required to form the membranes to shift the peak because the shift occurred in 60% MeOH but did not by the treatment with detergents or in 90% MeOH in which EYPC did not form the membranes. The molar absorption coefficient (Ɛ 610) was 32,700 M⁻¹ cm⁻¹, which was about twice the molar absorption co efficient (Ɛ 560) reported. We applied this method to the assay of PC-OOH prepared from EYPC and obtained the molar absorption coefficients (Ɛ 610), which were 79,100 and 115,700 M⁻¹ cm⁻¹ in the presence and absence of BHT, respectively. This finding allows the determination of PC-OOH concentration even in chemically complex systems.8 page(s

Measurement of Lipid Hydroperoxides by the Ferric-Xylenol Orange Method (1) Characteristics of the Ferric-Xylenol Orange/Membrane Phosphatidylcholine Complex

The ferric-xylenol orange (FOX) method for measurement of hydroperoxides is based on a technique that employs reduction of peroxides in an acidic condition by Fe2+ and formation of the colored ferric-xylenol orange (XO/Fe3) product with a peak at 560 nm. The 560 nm absorbance peak of XO/Fe3+ shifts to a 610 nm peak with high absorption intensity in the presence of phosphatidylcholine. This is useful for quantification of peroxides such as phospholipid hydroperoxides. Based on this finding, we recently reported a modified FOX method. We now show by measurements of absorbance, broadening of the electron paramagnetic resonance spectrum, changes in the vesicle size and their zeta potentials, the effects of detergents, and manipulation of the membrane lipid composition that the XO/Fe3 -phosphatidylcholine complex forms only in the presence of intact phosphatidylcholine membranes. The phosphate group on the phospholipid plays a role in this interaction which may involve an electron transfer from the phosphate to the Fe3+. A positively charged quaternary amine on the phosphatidylcholine is also necessary to give a peak absorbance at 610 nm. Our observations are consistent with binding of one X0/Fe3+ COmplex to about 3 molecules of the egg yolk phosphatidylcholine carrying a zero net charge.6 page(s

Efficient Intramolecular Cyclizations of Phenoxyethynyl Diols into Multisubstituted α,β-Unsaturated Lactones

AgOTf-catalyzed intramolecular cyclization of phenoxyethynyl diols proceeded under mild conditions to afford the multisubstituted α,β-unsaturated-γ-lactones in 55–98% yields. This method was also applicable to the synthesis of α,β-unsaturated-δ-lactones. A similar cyclization proceeded when AgOTf was replaced with a stoichiometric amount of <i>N</i>-bromosuccinimide to furnish the α-bromo-substituted α,β-unsaturated lactones

Anomalous Dependence of Translational Diffusion on the Water Mole Fraction for Solute Molecules Dissolved in a 1‑Butyl-3-methylimidazolium Tetrafluoroborate/Water Mixture

Translational diffusion coefficients of carbon monoxide (CO), diphenylacetylene (DPA), and diphenylcyclopropenone (DPCP) were determined in mixtures of 1-butyl-3-methylimidazolium tetrafluoroborate ([C4mim]BF4) and water using transient grating spectroscopy at different mole fractions of water (xw). While DPA exhibited a larger diffusion coefficient than DPCP at low water mole fractions (xw < 0.7), as observed for conventional liquids and ionic liquids (ILs), it was smaller at high mole fractions (xw > 0.9). The apparent molecular radius of DPA determined using the Stokes–Einstein equation at xw > 0.9 is close to the radius of an IL cluster in a water pool as determined from small-angle neutron scattering experiments (J. Bowers et al., Langmuir, 2004, 20, 2192–2198), suggesting that the DPA molecules are trapped in IL clusters in the water pool and move together. The solvation state of DPCP in the mixture was studied using Raman spectroscopy. Dramatically strong water/DPCP hydrogen bonding was observed at higher water mole fractions, suggesting that DPCP is located near the cluster interfaces. The large diffusion coefficient of DPCP suggests that hopping of DPCP between IL clusters occurs through hydrogen bonding with water

腎細動脈のヒアリノーシスは、大動脈の内膜肥厚とは異なり、腎生検で証明された糖尿病性腎症患者の心血管イベントに関連する。

Aims: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. Methods: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy‐proven diabetic nephropathy, with a median follow‐up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. Results: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow‐up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan–Meier analysis than those without these lesions (P = 0.005, log‐rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. Conclusions: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.博士（医学）・乙第1464号・令和2年9月30日© 2020 Diabetes UKThis is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/dme.14301], which has been published in final form at [https://doi.org/10.1111/dme.14301]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions