Absorption characteristics of compounds with different molecular weights after application to the unilateral kidney surface in rats

The aim of the present study is to clarify the absorption mechanism of a drug from the kidney surface membrane in rats. We studied the absorption characteristics of phenolsulfonphthalein (PSP) and other compounds with different molecular weights after their application to the rat kidney surface in vivo, employing a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm2). The time course of free PSP amounts remaining in the diffusion cell obeyed first-order kinetics at a dose of 1 mg, and its rate constant ka was calculated to be 0.0137 min?1. Absorption ratios of PSP in 4 h were calculated (from the amount recovered from the diffusion cell) to be 91.4, 96.4 and 97.7% at doses of 0.5, 1 and 1.5 mg, respectively. The area under the curve for the plasma concentration profile of free PSP was proportional to the application dose. It is thus suggested that the absorption process of PSP from the rat kidney surface does not approach saturation at a dose of 1.5 mg. Also, no significant difference was seen in the ka values within the dose range of 0.5?1.5 mg, which were estimated by curve-fitting the plasma concentration profiles of free PSP in a two-compartment model with first-order absorption. Furthermore, we examined the importance of molecular weight on the absorption from the kidney surface using fluorescein isothiocyanate-dextrans (FDs) with molecular weights of 4400 (FD-4), 11,000 (FD-10), 40,500 (FD-40) or 69,000 (FD-70), including the organic anions bromphenol blue and bromosulfonphthalein. The absorption ratios of FDs from the rat kidney surface in 6 h decreased with an increase in the molecular weight (76.1% for FD-4, 54.4% for FD-10, 11.5% for FD-40 and 3.9% for FD-70). A linear relationship was observed between ka and the reciprocal value of z the square root of the molecular weight of these compounds. The limit of absorption from the rat kidney surface was extrapolated to be at a molecular weight of approximately 130,000

Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition)

The version of record of this article, first published in Annals of Nuclear Medicine, is available online at Publisher’s website: https://doi.org/10.1007/s12149-024-01916-6.Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients’ caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer

sdLDL-C and Cardiovascular Events

Aim: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. Methods: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. Results: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. Conclusions: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL

Diagnostic Criteria of FMD and NID

Background - Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results - We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions - We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects

A design methodology for approximate multipliers in convolutional neural networks: A case of MNIST

In this paper, we present a case study on approximate multipliers for MNIST Convolutional Neural Network (CNN). We apply approximate multipliers with different bit-width to the convolution layer in MNIST CNN, evaluate the accuracy of MNIST classification, and analyze the trade-off between approximate multiplier’s area, critical path delay and the accuracy. Based on the results of the evaluation and analysis, we propose a design methodology for approximate multipliers. The approximate multipliers consist of some partial products, which are carefully selected according to the CNN input. With this methodology, we further reduce the area and the delay of the multipliers with keeping high accuracy of the MNIST classification

Combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular subtype after inferior vena cava stent placement for a patient with Budd–Chiari syndrome

We report a case of combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular subtype arising about 15 years after placement of an inferior vena cava stent for primary Budd–Chiari syndrome. Pre-surgical differentiation of the tumor from hepatocellular carcinoma was difficult because of elevated levels of alpha-fetoprotein and hypervascularity in the arterial phase. Histopathological examination revealed atypical cells forming ductal and alveolar structures showing a vague border with the surrounding liver. Immunostaining showed positive results for epithelial membrane antigen, mainly localized to the apical surface of the tubules, representing a characteristic finding for combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular subtype. Combined hepatocellular-cholangiocarcinoma with stem cell features arising in the liver with hepatic damage from Budd–Chiari syndrome is not common, but diagnosis is important to manage the malignancy, which shows different clinical behaviors from hepatocellular carcinoma