Prediction of color changes in acetaminophen solution using the time–temperature superposition principle

A prediction method for color changes based on the time–temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l’Eclairage (CIE) LAB color space (a*, b*, L* and ΔE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time–temperature shift factor of a*, b*, L* and ΔE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and ΔE*ab at 40?°C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R² values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time.     

三波长分光光度法测定小儿退热栓中扑热息痛的含量

本文介绍了用氯仿－无水乙醇作为溶剂，不经分离提取，利用ＵＶ－１６０Ａ分光光度计（注：机内带电脑）进行三波长分光光度法测定，排除小儿退热栓中基质和微量抗氧剂的干扰，直接测定扑热息痛的含量，此法简单，快速和准确。     

Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization,in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68⁺ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-γ and TNF-α, whereas CD163⁺ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204⁺ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B⁺ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.     

基于代谢组学研究对乙酰氨基酚片对中国健康成人胆汁酸谱的影响

目的：研究健康成人多次口服对乙酰氨基酚片后胆汁酸代谢的变化。方法：招募10名健康受试者,收集受试者口服对乙酰氨基酚前后的血清标本,分为给药前组（PD）,第5次给药后组（FD）及第8次给药后组（ED）,采用高效液相串联质谱（LC-MS/MS）的方法,定量检测血清胆汁酸谱,并结合代谢组学的主成分分析（PCA）,正交偏最小二乘法判别分析（OPLS-DA）,研究多次口服对乙酰氨基酚后健康成人胆汁酸代谢谱的变化,检测各组肝功能生化指标,观察在给药前后肝功能生化指标的变化。 结果：在给药前和给药后人血清的胆汁酸谱发生了变化,牛磺鹅去氧胆酸（TCDCA）,甘氨胆酸（GCA）,甘氨鹅脱氧胆酸（GCDCA）,牛磺熊去氧胆酸（TUDCA）的浓度与给药前的基线相比显著升高（P<0.05）,肝功能生化指标无明显的变化。采用代谢组学的方法筛选出的差异代谢物GCA,GCDCA为口服对乙酰氨基酚后胆汁酸改变最敏感的指标。结论：GCA和GCDCA或可作为对乙酰氨基酚致早期肝损伤的潜在生物标志物。     

HPLC法测定药物共晶中茶碱和对乙酰氨基酚的研究

建立了高效液相色谱法分离茶碱和对乙酰氨基酚双组分体系的最佳条件是:C18色谱柱(250 mm×4.6 mm,5μm,120),以十八烷基键合硅胶为固定相;流动相为0.01 mol/L磷酸二氢钾溶液(用磷酸溶液调节pH至3.05)(A)-甲醇(B)(体积比为80∶20);检测波长为245 nm和270 nm;流速为1.0 mL/min;柱温为25℃;进样量为20μL。实验结果表明:对乙酰氨基酚回归方程为y=0.651 1x+6.610 4,R2=0.994 5;茶碱回归方程为y=0.939 2x-5.575 1,R2=0.998,他们的线性范围是5~500μg/mL。该方法为茶碱、对乙酰氨基酚双组分体系研究提供依据,为其溶解度的测定提供方法支撑,作为高效液相色谱分离方法,分析快速,灵敏度高,重现性好。     

Electrochemical waste water treatment: Electrooxidation of acetaminophen

Oxidation of acetaminophen at boron-doped diamond (BDD) and at Ti/SnO₂ anodes in a plug-flow divided electrochemical reactor led to electrochemical combustion, whereas at Ti/IrO₂ benzoquinone was the exclusive product except at very long electrolysis times. The difference is explicable in terms of the different mechanisms of oxidation: direct oxidation at the anode for Ti/IrO₂ vs. indirect oxidation involving electrogenerated hydroxyl radicals at BDD and Ti/SnO₂. At BDD, at which the efficiency of degradation of acetaminophen was greatest, the rate of electrolysis at constant concentration was linearly dependent on the current, and at constant current linearly dependent on the concentration. Current efficiencies for mineralization up to 26% were achieved without optimization of the cell design.     

凝胶包埋大鼠肝细胞用于醋氨酚肝毒性研究

以传统的多孔板贴壁培养为比较对象，采用醋氨酚为肝毒性药物模型,评价胶原凝胶包埋培养大鼠肝细胞用于药物肝毒性研究的可行性.结果发现，虽然多孔板培养和凝胶包埋培养肝细胞均表现出对醋氨酚肝毒性的浓度依赖性，但前者对毒性的敏感程度比后者小得多.在同样低浓度（2.5 mmol/L）的醋氨酚作用24 h后，胶原凝胶包埋的细胞活率下降到了对照组的35％，单层贴壁培养细胞的活率仅下降到了对照组的88％；以尿素和白蛋白合成能力表征的肝功能也出现同样趋势.此外，N-乙酰半胱氨酸（NAC）与甘草酸（GA）与醋氨酚一起加到培养基中能显著抑制醋氨酚导致的肝毒性，进一步说明凝胶包埋培养肝细胞可以反映保肝药物的临床作用.     

离子液体-石墨烯修饰碳纤维微电极电化学研究

实验制备了离子液体-石墨烯修饰碳纤维微电极,采用循环伏安法和差分脉冲伏安法测定对乙酰氨基酚(ACOP)在该修饰电极上的电化学行为。结果显示,修饰后电极的稳定性和重现性明显增加。ACOP在修饰电极上的氧化峰电流与扫速的平方根基本成正比,氧化过程受扩散控制。采用差分脉冲伏安法测定ACOP标准品梯度浓度溶液,在5×10-7~1×10-4mol/L浓度范围内,其氧化峰电流与其浓度呈现良好的线性关系良好。     

Importance of Kupffer Cells in the Development of Acute Liver Injuries in Mice

Kupffer cells reside within the liver sinusoid and serve as gatekeepers. They produce pro- and anti-inflammatory cytokines and other biologically important molecules upon the engagement of pattern recognition receptors such as Toll-like receptors. Kupffer cell-ablated mice established by in vivo treatment with clodronate liposomes have revealed many important features of Kupffer cells. In this paper, we review the importance of Kupffer cells in murine acute liver injuries and focus on the following two models: lipopolysaccharide (LPS)-induced liver injury, which is induced by priming with Propionibacterium acnes and subsequent challenge with LPS, and hypercoagulability-mediated acute liver failure such as that in concanavalin A (Con A)-induced hepatitis. Kupffer cells are required for LPS sensitization induced by P. acnes and are a major cellular source of interleukin-18, which induces acute liver injury following LPS challenge. Kupffer cells contribute to Con A-induced acute liver failure by initiating pathogenic, intrasinusoidal thrombosis in collaboration with sinusoidal endothelial cells. The mechanisms underlying these models may shed light on human liver injuries induced by various etiologies such as viral infection and/or abnormal metabolism.