Exploring the mechanism of interaction between 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one and human serum albumin: Spectroscopic, calorimetric and molecular modeling studies

In this paper, binding interaction of 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (EMMD) with human serum albumin (HSA) under physiological conditions was investigated by using spectroscopy, isothermal titration calorimetry (ITC) and molecular modeling techniques. The results of spectroscopic studies suggested that EMMD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. ITC investigations indicated that drug-protein complex was stabilized by hydrophobic forces and hydrogen bonds, which was consistent with the results of molecular modeling studies. Competitive experiments indicated the displacement of warfarin by EMMD, which revealed that the binding site of EMMD to HSA was located at subdomain IIA.     

Anti-inflammatory property of n-hexadecanoic acid: structural evidence and kinetic assessment

Ester bond hydrolysis of membrane phospholipids by Phospholipase A₂ and consequent release of fatty acids are the initiating steps of inflammation. It is proposed in this study that the inhibition of phospholipase A₂ is one of the ways to control inflammation. Investigations are carried out to identify the mode of inhibition of phospholipase A₂ by the n‐hexadecanoic acid. It may help in designing of specific inhibitors of phospholipase A₂ as anti‐inflammatory agents. The enzyme kinetics study proved that n‐hexadecanoic acid inhibits phospholipase A₂ in a competitive manner. It was identified from the crystal structure at 2.5 Å resolution that the position of n‐hexadecanoic acid is in the active site of the phospholipase A₂. The binding constant and binding energy have also been calculated using Isothermal Titration Calorimetry. Also, the binding energy of n‐hexadecanoic acid to phospholipase A₂ was calculated by in silico method and compared with known inhibitors. It may be concluded from the structural and kinetics studies that the fatty acid, n‐hexadecanoic acid, is an inhibitor of phospholipase A₂, hence, an anti‐inflammatory compound. The inferences from the present study validate the rigorous use of medicated oils rich in n‐hexadecanoic acid for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda.     

Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease

OBJECTIVE: To assess the safety and tolerability of three different dosing schedules of memantine in patients with moderate to severe Alzheimer's disease (AD). METHOD: This 12-week, randomised, double-blind study, investigated three dosing schedules of memantine: OD1 (20 mg once daily with a 1-step up-titration); OD3 (20 mg once daily with a 3-step up-titration); and BID3 (10 mg twice daily with a 3-step up-titration as currently recommended in the memantine labelling). The study comprised 78 patients with moderate to severe AD (DSM-IV-TR criteria; MMSE score < or = 18), 70% of whom were on stable dosing of acetylcholinesterase inhibitor (AChEI) initiated > or = 3 months prior to study start. Safety and tolerability were assessed by the number of withdrawals, adverse events (AEs) and monitoring of vital signs. RESULTS: The number of patient withdrawals was low: 3 of 27 in OD1, 1 of 25 in OD3 and 2 of 26 in BID3. One or more AEs were reported in 9 patients in OD1, 7 patients in OD3 and 12 patients in BID3. Most AEs were mild or moderate, and typical for the population studied; no clinically important differences in AEs or vital signs were observed between the different dosing schedules. There were no between-group differences in efficacy, as assessed by clinical global severity and clinical global change. These results are consistent with the good safety profile of memantine observed in larger studies. CONCLUSIONS: Although relatively small in size, the study indicates that once-daily dosing and twice-daily dosing of memantine are similar in terms of safety and tolerability.     

盐酸普罗帕酮含量测定方法改进

目的：建立盐酸普罗帕酮非水滴定中革除汞盐的含量测定方法。方法：采用以无水甲酸-醋酐（1：50）为溶剂的高氯酸电位滴定法。结果：革除汞盐后方法含量测定结果与原方法结果基本一致,可以代替原方法。结论：方法简便、易行,可用于盐酸普洛帕酮的质量控制。     

眼内灌注液中氯化钙含量测定方法改良

目的对眼内灌注液中氯化钙含量测定终点判断方法的改良。方法按文献[1]方法加入试剂和被测物,然后加热再按规定测定氯化钙含量。结果测定终点突跃明显,终点容易判断,误差较小。结论本方法准确可靠。     

Study of the Adhesion of Neurodegenerative Proteins on Plasma-Modified and Coated Polypropylene Surfaces

Abstract

The inner polymeric surface of an ELISA titration well is plasma-modified and coated with different surfactant molecules. The titration of neurodegenerative proteins markers (prion, Tau and β-synuclein), previously demonstrated as more efficient with such modified tubes, is related to the adhesion behaviour of these proteins and their corresponding capture antibodies. The adhesion process is studied in terms of anchoring and specific mechanisms. The proteins and antibodies binding onto such modified surfaces is related to the substrate hydrophilic character calculated from the angle contact measure, to the polymer surface charge measured through the streaming potential determination at different pH and the inner surface roughness determined from AFM images. Furthermore, the influence of the blocking agent used during the ELISA titration is also studied.     

桂益嗪片、服止宁片含量测定法的改进

服止宁片的含量测定采用分光光度法吸收系数太小(E_(1cm)~(1%)=10.7),采用示波极谱滴定法终点较直观。但用与原料药含量测定方法一致的非水滴定法,可消除某些可能的系统误差。此法简便、可靠。本文报告用适量酒石酸掩蔽消除片剂辅料中硬脂酸镁等碱性辅料的干扰,且无须事先分离提取,可用非水滴定法直接测定片剂的含量。     

A simplified method for the preparation of EAC14 intermediate cells using human serum treated with methylprednisolone

The inhibitory effect of methylprednisolone 21-succinate ester (MPS) on the activities of complement components in human serum was studied by incubating human serum with various concentrations of MPS at 37 degrees C for 30 min and then measuring the residual activity of each component in human serum. The formation of EAC1 and EAC14 by C1 and C4 respectively, were only weakly inhibited by MPS at a final concentration of 10 mg/ml. In contrast, the same concentration of MPS completely inhibited the capacity of C2, C3, C5 and C6-9 to induce respective succeeding intermediates. On the basis of these findings a simplified method was devised for the preparation of EAC14 intermediates using human serum pretreated with MPS.     

双突跃电位滴定法测定壳聚糖脱乙酰度的影响因素

研究了双突跃电位滴定法测定壳聚糖脱乙酰度的准确性以及壳聚糖溶液质量浓度、粘度、不同脱乙酰度等因素对滴定终点测定结果的影响.结果表明:壳聚糖样品质量浓度控制在2～6g/L,利用双突跃电位滴定法可以测定壳聚糖的脱乙酰度,不同样品脱乙酰度测定结果RSD(相对标准偏差)小于0.61%(n=3),该方法具有较高地准确性,可以用于壳聚糖生产和加工过程中的质量控制与检测.