聚氯乙烯中环氧大豆油的迁移

基于分子结构力学方法,应用APDL（ANSYS Parametric Design Language）参数化编程,建立了含S W（Stone Wales）缺陷的单壁碳纳米管有限元模型。提出方向角的概念以表征缺陷的不同类型。对一系列含S W缺陷的单壁碳纳米管进行轴向拉伸和纯扭转的仿真计算,揭示出缺陷类型、数量和排列方式对其力学性能的影响规律。结果表明,弹性和剪切模量都会因缺陷的存在而出现不同程度的折损,特殊情况下反而上升,可从能量观点加以解释。缺陷的类型和排列方式决定其对弹性和剪切模量的影响趋势;当缺陷的类型和排列方式一定时,弹性和剪切模量的折损率与缺陷数量大致成正比。所得结论对实际含缺陷碳纳米管力学性能的评估和缺陷状况的预测均具有指导意义。     

含黄芩苷注射剂中突发性热原污染的去除研究

目的 优选含黄芩苷的注射剂中突发性污染的热原去除工艺。方法 采用动态浊度法和HPLC法检测不同浓度活性炭及不同截留分子量的超滤膜使用前后黄芩苷药液中细菌内毒素及有效成分含量,分别计算细菌内毒素去除率和黄芩苷回收率。结果 在热原突发污染情况下,测得0.10%,0.50%,1.00% 3种浓度活性炭对黄芩苷药液的细菌内毒素去除率分别为80.2%,91.7%和95.6%,同时黄芩苷回收率分别为90.8%,73.1%和51.3%;黄芩苷药液经5和10 kDa相对截留分子量的超滤膜的细菌内毒素去除效率均接近100%,黄芩苷回收率分别为52.6%和94.3%。结论 该实验明确了各种浓度活性炭都不能有效去除黄芩苷类药液的热原且对黄芩苷吸附率很高,而超滤法对黄芩苷药液热原的去除效果较好且成分回收率也很高,为中药注射剂生产工艺中去除热原提供依据。     

地塞米松对一氧化碳中毒迟发性脑病患者脑脊液中转化生长因子β_1与结缔组织生长因子的干预及意义

目的研究地塞米松对一氧化碳中毒迟发性脑病(DEACMP)患者脑脊液中转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)的干预及其意义。方法选取35例DEACMP患者为观察组,入院第1天、第29天留取脑脊液,并于第1天及之后隔日1次椎管注射地塞米松。同时选取35例同期入院的神经系统非脱髓鞘疾病患者为对照组,于入院第1天留取脑脊液。用酶联免疫吸附法测定脑脊液TGF-β1、CTGF水平;2组患者均于入院第1天行头颅CT。入院第29天判定疗效。结果观察组患者头颅CT均显示不同程度的脑室周围白质脱髓鞘改变;对照组患者头颅CT未见脑室周围白质脱髓鞘改变。与对照组入院第1天时比较,观察组入院第1天和第29天时脑脊液TGF-β1、CTGF水平均显著增高,差异均有统计学意义(P<0.05);观察组入院第29天时脑脊液TGF-β1、CTGF水平均显著低于入院第1天时,差异均有统计学意义(P<0.05)。结论 DEACMP患者发病机制可能与TGF-β1、CTGF过表达有关。地塞米松可能通过抑制TGF-β1、CTGF的过表达起到治疗DEACMP的作用。     

高动脉血二氧化碳分压延长顺式阿曲库铵肌松效果

目的:观察动脉血二氧化碳分压(PaCO2)对顺式阿曲库铵肌松效果的影响。方法:择期全麻下腹腔镜胆囊切除手术患者60例,年龄18～60岁,体重指数(BMI)18～24 kg/m2,ASAⅠ～Ⅱ级,随机分为A组(PaCO2控制目标为30～35 mmHg);B组(PaCO2控制目标为45～50 mmHg),每组30例。TOF-Watch加速度仪监测肌松。咪哒唑仑、芬太尼、丙泊酚和顺式阿曲库铵0.15 mg/kg(3ED95)静注行常规麻醉诱导气管插管。记录顺式阿曲库铵肌松最大作用持续时间、恢复指数及T1自25%至TOF中第4个肌颤搐与第1个肌颤搐的比值(TOFR)为0.9的恢复时间。结果:两组患者一般资料差异无统计学意义(P>0.05)。A、B两组肌松达到最大作用持续时间差异无统计学意义,A组恢复指数和T1自25%至TOFR为0.9的恢复时间均明显短于B组(P<0.05)。结论:高动脉血二氧化碳分压延长顺式阿曲库铵神经肌肉阻滞恢复时间。     

Synthesis of selectively labeled histidine and its methylderivatives with deuterium,tritium, and carbon‐14

Isotopologues of l ‐histidine and its N‐methylderivatives labeled with deuterium and tritium at the 5‐position in the imidazole ring were obtained using the isotope exchange method. The deuterium‐labeled isotopologues [5‐²H]‐l ‐histidine, [5‐²H]‐N^τ‐methyl‐l ‐histidine, [5‐²H]‐N^π‐methyl‐l ‐histidine, and [2,5‐²H₂]‐l ‐histidine were synthesized by isotope exchange method carried out in a fully deuterated medium with. The same reaction conditions were applied to synthesize [5‐³H]‐N^τ‐methyl‐l ‐histidine, [5‐³H]‐N^π‐methyl‐l ‐histidine, and [5‐³H]‐l ‐histidine with specific activity of 2.0, 5.0, and 2.6 MBq/mmol, respectively. The N^π‐[methyl‐¹⁴C]‐histamine was obtained with specific activity of 0.23 MBq/mmol in a one‐step reaction by the direct methylation of histamine by [¹⁴C]iodomethane.     

Gram‐scale synthesis and efficient purification of 13C‐labeled levoglucosan from 13C glucose

¹³C‐Labeled levoglucosan has been synthesized and purified in good yield, and on the gram scale in one step from commercially available ¹³C glucose. This one‐step protocol uses 2‐chloro‐1,3‐dimethylimidazolinium chloride that serves to selectively activate the anomeric carbon toward substitution reactions. The labeled glucose is then smoothly converted to the anhydroglucose. Purification is efficiently achieved on large scale by chromatography on silica gel.     

An alternative and robust synthesis of [13C4]Baraclude® (entecavir)

Stable isotope‐labeled [¹³C₄]entecavir (1) was prepared in 11 steps. Commercially available [¹³C]guanidine hydrochloride and diethyl[1,2,3‐¹³C₃]malonate were condensed to yield 2‐amino[2,4,5,6‐¹³C₄]pyrimidine‐4,6‐diol (8). This was converted to the desired purine (7) in five steps. Introduction of the chiral epoxide was followed by subsequent deprotection to give [¹³C₄]entecavir (1), in an overall yield of 5.7% from labeled precursors. The chemical purity of the title compound was determined to be >99% by HPLC. The isotopic distribution was determined by mass spectrometry to be 282[M + 4], 98.4%; 281[M + 3], 1.6%; and 278[M + 0], <0.1%. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of ozone and fine particulate matter (PM2.5) on rat system inflammation and cardiac function

In order to understand the toxic mechanisms of cardiovascular system injuries induced by ambient PM_2.5 and/or ozone, a subacute toxicological animal experiment was designed with exposure twice a week for 3 continuous weeks. Wistar rats were randomly categorized into 8 groups (n = 6): 1 control group, 3 groups exposed to fine particulate matters (PM_2.5) alone at 3 doses (0.2, 0.8, or 3.2 mg/rat), 1 group to ozone (0.81 ppm) alone and 3 groups to ozone plus PM_2.5 at 3 doses (0.2, 0.8, or 3.2 mg/rat). Heart rate (HR) and electrocardiogram (ECG) was monitored at approximately 24-h both after the 3rd exposure and the last (6th) exposure, and systolic blood pressure (SBP) was monitored at approximately 24-h after the 6th exposure. Biomarkers of systemic inflammation and injuries (CRP, IL-6, LDH, CK), heart oxidative stress (MDA, SOD) and endothelial function (ET-1, VEGF) were analyzed after the 6th exposure. Additionally, myocardial ultrastructural alterations were observed under transmission electron microscopy (TEM) for histopathological analyses. Results showed that PM_2.5 alone exposure could trigger the significant increase of CRP, MDA, CK, ET-1 and SBP and decrease of heart rate variability (HRV), a marker of cardiac autonomic nervous system (ANS) function. Ozone alone exposure in rats did not show significant alterations in any indicators. Ozone plus PM_2.5 exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose–response way. Meanwhile, abnormal ECG types were monitored in rats exposed to PM_2.5 with and without ozone and obvious myocardial ultrastructural changes were observed by TEM. In conclusion, PM_2.5 alone exposure could cause inflammation, endothelial function and ANS injuries, and ozone potentiated these effects induced by PM_2.5.     

Carboxylated mesoporous carbon microparticles as new approach to improve the oral bioavailability of poorly water-soluble carvedilol

The main objective of this study was to develop carboxylated ordered mesoporous carbon microparticles (c-MCMs) loaded with a poorly water-soluble drug, intended to be orally administered, able to enhance the drug loading capacity and improve the oral bioavailability. A model drug, carvedilol (CAR), was loaded onto c-MCMs via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The physicochemical properties of the drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and HPLC. It was found that c-MCM has a high drug loading level up to 41.6%, and higher than that of the mesoporous silica template. Incorporation of CAR in both drug carriers enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. After loading CAR into c-MCMs, its oral bioavailability was compared with the marketed product in dogs. The results showed that the bioavailability of CAR was improved 179.3% compared with that of the commercial product when c-MCM was used as the drug carrier. We believe that the present study will help in the design of oral drug delivery systems for enhanced oral bioavailability of poorly water-soluble drugs.     

NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination

Multi-walled carbon nanotubes (MWCNT) have been reported to cause lung pathologies in multiple studies. However, the mechanism responsible for the bioactivity has not been determined. This study used nine different well-characterized MWCNT and examined the outcomes in vitro and in vivo. MWCNT, from a variety of sources that differed primarily in overall purity and metal contaminants, were examined for their effects in vitro (toxicity and NLRP3 inflammasome activation using primary alveolar macrophages isolated from C57Bl/6 mice). In addition, in vivo exposures were conducted to determine the inflammatory and pathogenic potency. The particles produced a differential magnitude of responses, both in vivo and in vitro, that was associated most strongly with nickel contamination on the particle. Furthermore, the mechanism of action for the Ni-contaminated particles was in their ability to disrupt macrophage phagolysosomes, which resulted in NLRP3 activation and subsequent cytokine release associated with prolonged inflammation and lung pathology.