Characterization of human cartilage in degenerated spine disease with differential scanning calorimetry

The purpose of this study was to further characterize the altered metabolism spondylolisthesis that promotes disease progression. Degenerative human cartilage (intervertebral disc, facet joint and vertebral end-plate) was obtained during 15 posterior lumbar spine interbody fusion procedures performed at the University of Szeged. The thermal properties of samples were determined by differential scanning calorimetry (Mettler-Toledo DSC 821^e). Greatest change in the enthalpy was observed in the intervertebral disc samples: −1600.78 J g⁻¹. Denaturation caused by heating in the normal human hyaline cartilage needed −1493.31 J g⁻¹ energy. Characterization of the altered metabolism that promotes disease progression should lead to future treatment options.     

Determination of intracellular glutathione and cysteine using HPLC with a monolithic column after derivatization with monobromobimane

An optimized high‐performance liquid chromatography (HPLC) method is used to show that, as myoblasts differentiate into multinucleated muscle fibers, there is a shift to a more oxidized cell redox state. The HPLC method incorporated derivatization with monobromobimane for the determination of the reduced (GSH) and oxidized (GSSG) forms of glutathione and the reduced (Cys) and oxidized (CysSS) forms of cysteine. The derivatization was optimized to improve the sensitivity of the approach; the limits of detection for glutathione and cysteine were 3 × 10^?8 and 5 × 10^?8 M , respectively. Copyright © 2009 John Wiley & Sons, Ltd.     

中国数字人体男性数学模型建立及外辐射模拟

基于中国数字人男一号高分辨人体结构数据集，通过最小包围盒方法获取中国数字人体男性体素模型各器官空间位置和尺寸信息，建立了中国数字人体男性数学模型，并通过变形实现了不同身高模型的构建。采用蒙特卡罗方法进行了不同能量下光子中子的外部辐射模拟。通过结果对比发现，数学模型与体素模型模拟结果趋势一致，但器官位置和质量对剂量影响较大，低能级下尤为明显。对于不同身高模型，小型个体剂量大于大型个体，深层器官剂量较浅层器官对器官尺寸更为敏感。数学模型定义简单，存储空间小，有利于人体辐射剂量的快速计算。     

人力资本与经济增长关系实证分析——以浙江省为例

本文针对浙江省人力资本水平与经济增长水平不相匹配的经济现象,利用浙江省1985—2004年统计数据,论证了浙江人力资本与经济增长之间的关系.通过建立人力资本评价体系,运用因子分析法测算出浙江人力资本综合指数H;运用计量分析方法,论证了人力资本与经济增长之间存在着长期协整关系;通过建立模型,得出以下基本结论:浙江人力资本对经济增长有显著影响,其人力资本的产出弹性大于物资资本的产出弹性,简单劳动力的产出弹性为负值,表明人力资本对经济增长的拉动力要大于物质资本,简单劳动力已经处于过剩或饱和状态,提高劳动力素质尤为重要.对此,本文提出了相应的政策建议.     

Identification and structural elucidation of in vitro metabolites of atazanavir by HPLC and tandem mass spectrometry

Atazanavir (marketed as Reyataz®) is an important member of the human immunodeficiency virus protease inhibitor class. LC‐UV‐MSⁿ experiments were designed to identify metabolites of atazanavir after incubations in human hepatocytes. Five major (M1–M5) and seven minor (M7–M12) metabolites were identified. The most abundant metabolite, M1, was formed by a mono‐oxidation on the t‐butyl group at the non‐prime side. The second most abundant metabolite, M2, was also a mono‐oxidation product, which has not yet been definitively identified. Metabolites, M3 and M4, were structural isomers, which were apparently formed by oxidative carbamate hydrolysis. The structure of M5 comprises the non‐prime side of atazanavir which contains a pyridinyl‐benzyl group. Metabolite M6a was formed by the cleavage of the pyridinyl‐benzyl side chain, as evidenced by the formation of the corresponding metabolic product, the pyridinyl‐benzoic acid (M6b). Mono‐oxidation also occurred on the pyridinyl‐benzyl group to produce the low abundance metabolite M8. Oxidation of the terminal methyl groups produced M9 and M10, respectively, which have low chemical stability. Trace‐level metabolites of di‐oxidations, M11 and M12, were also detected, but the complexity of the molecule precluded identification of the second oxidation site. To our knowledge, metabolites M6b and M8 have not been reported. Copyright © 2013 John Wiley & Sons, Ltd.     

LC‐MS/MS determination and pharmacokinetic study of lacidipine in human plasma

A robust, specific and fully validated LC‐MS/MS method as per general practices of industry has been developed for estimation of lacidipine (LAC) with 100 μL of human plasma using lacidipine‐¹³C8 as an internal standard (IS). The API‐4000 LC‐MS/MS was operated under the multiple reaction‐monitoring mode. A simple liquid–liquid extraction process was used to extract LAC and IS from human plasma. The total run time was 3.0 min and the elution of LAC and IS occurred at 1.96 and 1.97 min; this was achieved with a mobile phase consisting of 5 mm ammonium acetate buffer–acetontrile (15:85 v/v) at a flow rate of 0.60 mL/min on a Zorbax SB C₁₈ (50 × 4.6 mm, 5 µm) column. A linear response function was established for the range of concentrations 50–15,000 pg/mL (r > 0.998) for LAC. The current developed method has negligible matrix effect and is free from unwanted adducts and clusters which are formed owing to system such as solvent or mobile phase. The developed assay method was applied to an oral pharmacokinetic study in humans and successfully characterized the pharmacokinetic data up to 72 h. Copyright © 2013 John Wiley & Sons, Ltd.     

Rapid and sensitive LC‐MS/MS method for determination of megestrol acetate in human plasma: application to a human pharmacokinetic study

A rapid, simple and fully validated LC‐MS/MS method was developed and validated for the determination of megestrol acetate in human plasma using tolbutamide as an internal standard (IS) after one‐step liquid–liquid extraction with methyl‐tert‐butyl‐ether. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 385.5 → 267.1 for megestrol acetate and m/z 271.4 → 155.1 for IS. Chromatographic separation was performed on a YMC Hydrosphere C₁₈ column with an isocratic mobile phase, which consisted of 10 mm ammonium formate buffer (adjusted to pH 5.0 with formic acid)–methanol (60:40, v/v) at a flow rate of 0.4 mL/min. The achieved lower limit of quantitation (LLOQ) was 1 ng/mL (signal‐to‐noise ratio > 10) and the standard calibration curve for megestrol acetate was linear (r > 0.99) over the studied concentration range (1–2000 ng/mL). The proposed method was fully validated by determining its specificity, linearity, LLOQ, intra‐ and inter‐day precision and accuracy, recovery, matrix effect and stability. The validated LC‐MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of megestrol acetate after oral administration of a single dose 800 mg of megestrol acetate (Megace?) to five healthy Korean male volunteers under fed conditions. Copyright © 2012 John Wiley & Sons, Ltd.     

Simultaneous determination of sitagliptin and simvastatin in human plasma by LC‐MS/MS and its application to a human pharmacokinetic study

A simple, rapid and sensitive liquid chromatography–tandem mass spectrometric (LC‐MS/MS) assay method has been developed and validated for simultaneous quantification of sitagliptin and simvastatin in human plasma. Carbamazepine was used as an internal standard (IS). The analytes and IS were extracted from the human plasma by liquid–liquid extraction technique. The reconstituted samples were chromatographed on an Alltima HP C₁₈ column using an isocratic solvent mixture [acetonitrile–5 mm ammonium acetate (pH 4.5), 85:15 (v/v)] at a flow rate of 1.0 mL/min. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curves obtained were linear (r² ≥ 0.99) over the concentration range of 0.10–501 and 0.05–105 ng/mL for sitagliptin and simvastatin, respectively. The results of the intra‐ and inter‐day precision and accuracy studies were well within the acceptable limits. Both the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 3.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay was successfully applied to a pharmacokinetic study in human volunteers. Copyright © 2012 John Wiley & Sons, Ltd.     

Weighted risk capital allocations

By extending the notion of weighted premium calculation principles, we introduce weighted risk capital allocations, explore their properties, and develop computational methods. When achieving these goals, we find it particularly fruitful to relate the weighted allocations to general Stein-type covariance decompositions, which are of interest on their own.     

Using Ho3+ Fluorescence Enhancement as a Novel Probe in Monitoring of Human Serum Albumin

Abstract

In this work, for the first time, the fluorescence enhancement of Ho³⁺ ions is introduced as a novel probe for human serum albumin (HSA) determination in aqueous solution. Lanthanides express very specific luminescence emissions, due to their unfilled 4fⁿ electronic orbital, and thus, the fluorescence of the lanthanide ions can be radically improved when they are coordinated with the appropriate organic molecules. By applying this method, HSA can be determined up to 0.066 mg L^?1.