RBL-2H3细胞脱颗粒模型评价注射用丹参多酚酸的安全性

目的 通过RBL-2H3肥大细胞脱颗粒模型考察注射用丹参多酚酸及丹参多酚酸B、D的致敏性。方法 RBL-2H3肥大细胞分为对照（PBS）组、C48/80 （阳性对照,4 mg/mL）组和梯度浓度（0.025、0.050、0.100、0.200、0.400、0.800 mg/mL）的注射用丹参多酚酸、丹参多酚酸B、丹参多酚酸D组,孵育30 min后,通过中性红染色试验观察脱颗粒现象,化学荧光法测定组胺释放率,酶联免疫吸附（ELISA）法测定β-氨基己糖苷酶释放率、类胰蛋白酶释放量。结果 与对照组比较,阳性药C48/80组、质量浓度≥0.2 mg/mL的丹参多酚酸B组、质量浓度≥0.4 mg/mL的丹参多酚酸D组、质量浓度为0.8 mg/mL的注射用丹参多酚酸组的细胞脱颗粒度显著升高（P<0.01、0.05）;注射用丹参多酚酸没有引起RBL-2H3细胞组胺释放率增加,C48/80组、质量浓度≥0.025 mg/mL的丹参多酚酸D组、0.8 mg/mL的丹参多酚酸B组组胺释放率即显著升高（P<0.001、0.05）;注射用丹参多酚酸和丹参多酚酸B组类胰蛋白酶释放量无显著性差异,质量浓度≥0.025 mg/mL的丹参多酚酸D组类胰蛋白酶释放量显著增加（P<0.001）;注射用丹参多酚酸没有引起β-氨基己糖苷酶释放率增加,0.8 mg/mL的丹参多酚酸D组、质量浓度≥0.1 mg/mL的丹参多酚酸B组的β-氨基己糖苷酶释放率显著增加（P<0.001）。结论 注射用丹参多酚酸在致敏性方面有较好的安全性。     

注射用丹参多酚酸联合疏血通治疗脑梗死的疗效观察

目的 观察注射用丹参多酚酸联合疏血通治疗脑梗死的临床疗效。方法 将68例急性脑梗死患者随机分为两组,各34例。对照组用疏血通6 mL加0.9%氯化钠250 mL,静脉滴注,1次/d;观察组在对照组基础上加用注射用丹参多酚酸0.13 g加0.9%氯化钠250 mL,静脉滴注,1次/d,两组均治疗14 d,比较两组的临床有效率以及血液流变学指标。结果 治疗后,观察组临床总有效率79.41%,高于对照组的55.88%,观察组的临床疗效优于对照组的（P<0.05）;两组血液黏度、血浆黏度和血浆纤维蛋白原较治疗前均有改善（P<0.05）,且观察组改善程度较对照组更为显著（P<0.05）。结论 注射用丹参多酚酸联合疏血通治疗脑梗死能有效控制病情发展,疗效显著,值得临床推广。     

注射用丹参多酚酸治疗急性脑梗死患者的疗效评价

目的 观察注射用丹参多酚酸治疗急性脑梗死患者的临床疗效。方法 选择2017年11月-2018年6月在齐齐哈尔医学院附属第三医院进行诊治的急性脑梗死患者64例,随机分为对照组与观察组,各32例。对照组给予常规治疗,观察组在对照组基础上加用注射用丹参多酚酸,每次0.13 g加入250 mL 0.9%氯化钠中静滴,1次/d,疗程均为14 d。根据美国国立卫生研究院卒中量表（NIHSS）判定临床疗效,以改良Rankin量表（mRS）评价神经功能恢复情况。结果 治疗后,对照组与观察组的有效率分别为75%和91%,观察组的治疗有效率明显高于对照组（P<0.05）;观察组神经功能恢复明显高于对照组（P<0.05）。结论 注射用丹参多酚酸治疗急性脑梗死患者疗效明显,能促进神经功能改善,无明显副作用,值得临床推广。     

注射用丹参多酚酸对脑梗死患者的临床疗效观察

目的 分析注射用丹参多酚酸对脑梗死患者的临床疗效。方法 选取黑龙江省第二医院40例脑梗死患者,随机分为观察组和对照组,对照组给予常规治疗,观察组在对照组治疗基础上加用注射用丹参多酚酸100 mg,1次/d静滴,疗程14d。比较两组患者神经功能改善情况及两组患者治疗有效率。结果 观察组及对照组治疗前NIHSS评分比较无明显差异;治疗后,观察组及对照组NIHSS评分均低于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后观察组NIHSS评分低于对照组,两者比较有显著差异（P<0.05）。观察组治疗总有效率高于对照组,差异具有统计学意义（P<0.05）。结论 脑梗死患者早期应用丹参多酚酸可有效改善神经功能,具有良好疗效。     

注射用丹参多酚酸治疗急性缺血性脑卒中疗效与血清TLR4/NF-κB信号通路因子水平相关性临床研究

目的 探讨血清Toll样受体4（TLR4）/核转录因子-κB（NF-κB）信号通路因子水平与注射用丹参多酚酸治疗急性缺血性脑卒中疗效的关系,并探讨TLR4和NF-κB预测注射用丹参多酚酸治疗效果的应用价值。方法 前瞻性纳入2017年5月—2020年4月安阳市第六人民医院收治的急性缺血性脑卒中患者500例为研究对象,所有患者入院后予以吸氧、抗感染、降颅压等常规对症治疗,同时给予注射用丹参多酚酸0.13 g溶于0.9%氯化钠注射液250 mL中静脉滴注,滴速应≤40滴/min,1次/d;连续治疗2周。治疗结束,参照相关标准评估患者疗效,根据疗效将患者分为有效组（n=452）和无效组（n=48）;检测患者治疗前、治疗2周后血清TLR4、NF-κB水平,采集患者基线资料,采用Logistic回归分析血清TLR4、NF-κB水平与注射用丹参多酚酸治疗急性缺血性脑卒中疗效的关系,绘制受试者工作曲线（ROC）,并计算曲线下面积（AUC）值,以检验血清TLR4、NF-κB水平预测注射用丹参多酚酸治疗缺血性脑卒中无效风险价值。结果 500例急性缺血性脑卒中患者经注射用丹参多酚酸治疗2周后血清TLR4、NF-κB水平较治疗前显著降低（P<0.05）;疗效评估结果显示,500例急性缺血性脑卒中患者经注射用丹参多酚酸治疗后有效452例,总有效率为90.4%,无效48例,无效率为9.6%;无效组治疗后血清抑素C（Cys C）、TLR4、NF-κB水平均高于有效组（P<0.05）;经Logistic回归结果显示,Cys C、TLR4、NF-κB异常表达可能与急性缺血性脑卒中患者应用注射用丹参多酚酸治疗无效有关,3者过表达可能是急性缺血性脑卒中患者应用注射用丹参多酚酸治疗无效的风险因子（OR>1,P<0.05）;绘制ROC曲线发现,血清TLR4、NF-κB单一及联合预测注射用丹参多酚酸治疗急性缺血性脑卒中无效风险的AUC>0.80,有一定预测价值,且在二者cut-off值分别取3.955、121.103 ng/mL时,预测价值最佳。结论 部分急性缺血性脑卒中患者经注射用丹参多酚酸治疗无效,可能与患者血清TLR4、NF-κB过表达有关,考虑可将TLR4、NF-κB作为辅助评估急性缺血性脑卒中患者应用注射用丹参多酚酸治疗无效风险的重要指标。     

注射用丹参多酚酸对急性缺血性脑卒中的疗效分析研究

目的 研究注射用丹参多酚酸对急性缺血性脑卒中的临床疗效。方法 选取急性缺血性脑卒中患者200例,随机分为观察组和对照组,各100例。纳入研究的200例患者均给予常规抗凝[阿司匹林（100~300）mg/d]、降脂（阿托伐他汀20 mg/d）及非丹参类中成药进行治疗,观察组在此基础上再给予注射用丹参多酚酸100 mg/d静脉滴注。两组均以14 d为1个疗程,评价患者的临床疗效、神经功能缺损情况（NIHSS评分）、日常生活能力（ADL评分）。结果 观察组总有效率为91%,显著高于对照组的75%（P<0.05）。两组治疗前后比较,NIHSS评分明显降低,ADL评分明显升高,差异具有统计学意义（P<0.05）;治疗后观察组的NIHSS评分和ADL评分改善程度显著优于对照组（P<0.05）。结论 注射用丹参多酚酸对急性缺血性脑卒中神经功能的恢复有一定的促进作用。     

注射用丹参多酚酸对前循环急性脑梗死患者血清MMP-9的影响

目的 观察注射用丹参多酚酸治疗前循环急性脑梗死对患者血清基质金属蛋白酶-9（MMP-9）水平的影响。方法选取2017年1月—2018年12月郑州市第一人民医院治疗的112例前循环急性脑梗死患者,按照1∶1的比例随机分配到对照组和观察组。对照组给予缺血性脑血管病基础治疗,观察组在对照组治疗的基础上静脉滴注注射用丹参多酚酸,将0.13 g注射用丹参多酚酸溶于250 mL 0.9%氯化钠注射液中,1次/d。两组均以14 d为1个疗程。比较两组患者治疗前、治疗7 d及治疗14 d后血清MMP-9水平变化情况。结果 治疗7、14 d后,两组患者血清MMP-9水平均显著低于治疗前,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组患者血清MMP-9水平显著低于对照组,两组比较差异有统计学意义（P<0.05）。观察组患者治疗14 d后,血清MMP-9水平较治疗7 d后有显著降低（P<0.05）。结论 注射用丹参多酚酸治疗前循环急性脑梗死患者能够持久、有效的降低患者血清MMP-9水平,疗效确切。     

HPLC同时测定丹酚酸B和阿魏酸的含量

目的 建立HPLC同时测定丹酚酸B和阿魏酸的方法。方法 色谱柱ODS-C₁₈(4.6 mm×250 mm,5 μm)柱,流动相：甲醇-乙腈-甲酸-水,检测波长为286 nm,流速0.8 mL·min^-1。结果 丹酚酸B浓度在5.40~43.25 μg·mL^-1,阿魏酸浓度在3.37~27.00 μg·mL^-1内线性关系良好。丹酚酸B和阿魏酸的线性方程分别为：Y=0.971 1X-2.215 4,r=0.999 8,Y=0.415 9X-0.450 7,r=0.999 9;平均回收率分别为98.4%,98.7%;RSD分别为3.39%,1.49%。结论 本法在检测丹酚酸B和阿魏酸时有较好的专属性,灵敏度高,重复性好,且样品处理简单、容易操作,可以作为丹参和当归复方制剂的质量检测方法。     

注射用丹参多酚酸治疗急性脑梗死的临床疗效观察

目的 观察注射用丹参多酚酸治疗急性脑梗死的临床疗效。方法 选择发病时间在72 h内的急性脑梗死住院患者100例,随机分为观察组和对照组,每组50例。对照组给予抗血小板聚集、清除自由基等常规治疗,观察组在对照组治疗基础上给予注射用丹参多酚酸130 mg,溶于0.9%氯化钠注射液250 mL中静脉滴注,1次/d,两组均治疗14 d。治疗前后分别采用欧洲卒中分量表神经功能评分（ESS）和日常生活能力评分（Barthel ADL指数）进行判定,对两组的临床疗效进行比较。结果 治疗2周后,观察组总有效率90.0%,高于对照组的76.0%,两组比较差异有统计学意义（P<0.05）;观察组与对照组的ESS评分和Barthel ADL指数较治疗前均有改善,差异有统计学意义（P<0.05）,且观察组的优于对照组的（P<0.05）。结论 注射用丹参多酚酸对改善急性脑梗死患者的行为障碍和神经症状有较好的疗效。     

定量核磁共振技术测定注射用丹参多酚酸中咖啡酸、丹参素、原儿茶酸和阿魏酸

目的 建立定量核磁共振技术(qNMR)同时测定注射用丹参多酚酸中咖啡酸、丹参素、原儿茶酸和阿魏酸。方法 通过qNMR测定4种单体酚酸，脉冲序列^zg30抑制水峰，谱宽设定8 012.8 Hz，温度为25℃，采样点数为131 072，采集时间为4.09 s，弛豫延迟时间为8.26 s，纵向弛豫时间为1.25 s；采样次数为16，接收器增益值为35.6，数字化仪分辨率值为18，空扫次数为4，发射机频率偏移为6.0×10^-6。以三氟乙酸-d为内标，根据峰面积比与质量比计算4种单体酚酸的含量。结果 咖啡酸、丹参素、原儿茶酸、阿魏酸分别选取9.47×10^-6(s，H-7)、8.02×10^-6(s，H-8)、5.86×10^-6(s，H-8)、12.79×10^-6(s，H-8)处的信号为定量峰；分析物在12 h后稳定性较差，所有样品在制备后12 h内完成测定；咖啡酸在0.103～1.625 μg·mL^-1(r²=0.999 3)，丹参素在2.256～3.194 μg·mL^-1(r²=0.999 5)，原儿茶酸在9.699～13.584 μg·mL^-1(r²=0.999 8)，阿魏酸在1.566～2.649 μg·mL^-1(r²=0.999 6)均呈良好的线性关系；加样回收率分别为104.9%、101.5%、104.1%、101.4%，RSD值分别为1.6%、2.1%、2.3%、1.5%；精密度、准确性、重复性均良好。结论 建立的qNMR可同时测定注射用丹参多酚酸中咖啡酸、丹参素、原儿茶酸和阿魏酸。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.