丁苯酞序贯治疗大脑中动脉供血区急性梗死疗效观察

摘 要 目的：观察丁苯酞注射液及软胶囊对急性大脑中动脉供血区脑梗死患者序贯治疗的有效性和安全性。方法: 61例起病72 h内,美国国立卫生研究院卒中量表（NIHSS）评分5～25分的左侧大脑中动脉供血区急性脑梗死患者随机分为观察组（n＝31）和对照组（n＝30）。对照组仅予常规治疗,观察组在常规治疗基础上序贯给予丁苯酞注射液及丁苯酞软胶囊治疗。疗程均为90 d。治疗前行NIHSS评分比较两组神经功能缺损程度,治疗后比较两组随访日常生活自理能力评定[Barthel指数（BI）和改良Rankin量表（mRS）],并记录两组药品不良反应。结果: 治疗前,两组患者NIHSS评分差异无统计学意义（P＞0.05）.治疗后观察组和对照组BI分别为（88.55+16.74）和（70.67+26.18）,mRS分别为（1.87+1.02）和（2.53+1.40）,观察组优于对照组（P＜0.05）,两组药品不良反应发生率相似。结论:丁苯酞序贯治疗急性脑梗死有效且安全,能改患者善日常生活能力,改善90 d远期预后。     

丁苯酞抑制趋化因子样因子1表达对大鼠局灶性脑缺血后脑水肿的影响

摘 要 目的：探究丁苯酞对大鼠局灶性脑缺血后脑水肿的影响,并初步探讨相关分子机制。方法: 建立大鼠局灶性脑缺血模型,再灌注6 h后,假手术组和模型组右侧脑室注射生理盐水（均为5 μl）,阳性对照组注射抗趋化因子样因子1（CKLF1）抗体（5 μl）,丁苯酞组注射丁苯酞（5 μl）。再灌注24 h后检测脑组织含水量;免疫组织化学染色法观察缺血右侧半球中性粒细胞浸润情况;采用ELISA、蛋白免疫印迹、实时定量PCR检测缺血半球肿瘤坏死因子（TNF α）、白细胞介素1（IL 1β）、趋化素样因子1（CKLF1）、细胞间黏附分子 1（ICAM 1）、血管细胞黏附分子 1（VCAM 1）表达。结果: 与左侧脑组织相比,模型组、阳性对照组、丁苯酞组大鼠右侧脑组织含水量显著增加（P＜0.05）,阳性对照组与丁苯酞组大鼠右侧脑组织含水量比较差异无统计学意义（P＞0.05）。与假手术组相比,模型组大鼠右侧脑组织含水量、CKLF1表达、TNF α和IL 1β含量、ICAM 1和VCAM 1表达、嗜中性粒细胞数目、MPO活性均显著增加（P＜0.05）。与模型组相比,阳性对照组和丁苯酞组大鼠右侧脑组织含水量、CKLF1表达、TNF α和IL 1β含量、ICAM 1和VCAM 1表达、嗜中性粒细胞数目、MPO活性均显著降低（P＜0.05）。与阳性对照组相比,丁苯酞组大鼠TNF α、IL 1β含量、嗜中性粒细胞数目、MPO活性均显著降低（P＜0.05）;而阳性对照组和丁苯酞组大鼠ICAM 1和VCAM 1 表达比较差异无统计学意义（P＞0.05）。结论: 丁苯酞可能通过抑制脑缺血大鼠脑组织中趋化因子CKLF1表达,降低脑缺血炎性损伤,改善缺血后脑水肿,从而发挥脑保护作用。     

丁苯酞联合脑循环治疗仪对急性脑梗死患者神经功能及脑循环状态的影响

摘 要 目的：探讨丁苯酞注射液联合脑循环治疗仪对急性脑梗死患者神经功能及脑循环状态的影响。方法: 120例急性脑梗死患者随机分为3组,每组40例。C组给予常规治疗;A组给予常规治疗＋丁苯酞注射液治疗;B组给予常规治疗＋丁苯酞注射液＋小脑电刺激治疗。3组均连续治疗21d。评估3组的临床疗效,比较3组治疗前后的NIHSS评分、改良Rankin量表（mRS）评分、双侧大脑中动脉峰值流速（Vp）、平均血流速度（Vm）、双侧差值(Dvp、Dvm)等脑血流动力学参数及血管搏动指数、脑循环储备功能的变化。结果: 治疗后,B组总有效率为92.5%,明显高于C组的72.5%（P＜0.05）。3组治疗后NIHSS、mRS评分均较治疗前明显下降(P＜0.05),且B组两项评分明显低于C组(P＜0.05)。3组治疗后Vp、Vm 均较前明显升高,DVp、DVm及血管搏动指数较前明显下降,脑循环储备功能明显改善(P＜0.05);A、B组各项参数均优于C组（P＜0.05）,且B组优于A组（P＜0.05）。结论: 丁苯酞注射液联合脑循环功能仪治疗可显著改善急性脑梗死患者的神经功能,纠正脑循环状态异常。     

丁苯酞辅助治疗对进展性脑梗死患者内皮祖细胞、碱性成纤维细胞生长因子及侧支循环影响的回顾性分析

摘 要 目的：探讨丁苯酞辅助治疗对进展性脑梗死患者内皮祖细胞(EPCs)、碱性成纤维细胞生长因子(bFGF)及侧支循环的影响。 方法：回顾性分析2015年1月～2017年7月我院住院治疗的进展性脑梗死患者89例的临床资料。根据用药方法分为对照组(n=40)和丁苯酞组(n=49)，对照组采用常规方法治疗，丁苯酞组在对照组基础上加用丁苯酞注射液25 mg，ivd，qd。两组患者均治疗14 d。比较两组治疗前后NIHSS评分、Barthel指数、梗死灶容积、临床疗效以及外周血 EPCs 数量、bFGF含量和侧支循环开放率。结果：丁苯酞组总有效率为83.7%，侧支循环开放率为79.6%，均显著高于对照组（P＜0.05）。治疗后，两组NIHSS 评分均较治疗前明显下降（P＜0.05），Barthel指数则较前明显增高（P＜0.05），梗死灶面积较前明显缩小（P＜0.05）；且丁苯酞组上述指标均优于对照组（P＜0.05）。治疗后，两组EPCs 数量、bFGF含量均较前明显升高（P＜0.05），且丁苯酞组EPCs数量及bFGF含量治疗前后变化值均显著大于对照组（P＜0.05）。结论：丁苯酞辅助治疗进展性脑梗死的疗效显著，可明显增加患者外周血EPCs 数量和bFGF含量，有利于侧支循环的建立和神经功能的改善。     

丁苯酞对急性进展性脑梗死患者血同型半胱氨酸、C反应蛋白及神经功能的影响

摘 要 目的： 探讨丁苯酞对急性进展性脑梗死患者血同型半胱氨酸（Hcy）、C反应蛋白（CRP）及神经功能的影响。方法: 122例急性进展性脑梗死患者随机分为观察组（n=60）和对照组（n=62）。对照组采用常规对症治疗,观察组在对照组基础上加用丁苯酞治疗。两组疗程均为2周。比较两组临床总有效率,以及两组患者治疗前后血Hcy、血浆CRP水平及神经功能缺损评分变化。结果: 观察组总有效率为81.67%,显著高于对照组的64.52%（P<0.05）。治疗后两组血Hcy、CRP均较治疗前显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）。两组神经功能缺损评分治疗后均较前显著降低（P<0.05）,且观察组显著低于同期对照组（P<0.05）。两组治疗期间均未发生明显不良反应。结论:丁苯酞对急性进展性脑梗死患者效果明显,可明显降低血Hcy、CRP水平,减少神经功能缺损评分,改善神经功能,且无明显不良反应。     

丁苯酞联合较高剂量阿托伐他汀治疗急性脑梗死临床观察

摘 要 目的：观察丁苯酞联合较高剂量阿托伐他汀治疗急性脑梗死的疗效,及对患者炎性反应、氧化应激和动脉粥样斑块的影响。 方法: 146例急性脑梗死患者随机分为观察组和对照组各73例。对照组给予丁苯酞联合常规剂量阿托伐他汀治疗,观察组给予丁苯酞联合较高剂量阿托伐他汀治疗。评价两组治疗总有效率,比较两组患者治疗前后血浆同型半胱氨酸(Hcy)、C 反应蛋白(CRP)、丙二醛（MDA）、超氧化物歧化酶(SOD)、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇(LDL C)、 氧化修饰低密度脂蛋白 （oxLDL）、基质金属蛋白酶 9(MMP 9)水平,和颈动脉内膜中层厚度(cIMT)、颈动脉粥样斑块面积、不稳定斑块数量变化情况。对Hey、MDA、斑块面积、不稳定斑块变化幅度与年龄、入院NHSS评分、脑梗死体积及丁苯酞联合降脂、联合一般降脂、联合强化降脂等指标的相关性进行分析。出院后进行3个月的预后随访。结果: 治疗后观察组总有效率为81.2%,明显高于对照组的61.4%（P＜0.05）。治疗后两组患者的Hcy、CRP、MDA、TC、TG、LDL、oxLDL、MMP 9、cIMT及颈动脉斑块面积、不稳定斑块数量等指标均较治疗前明显降低(P＜0.05),SOD则较治疗前升高(P＜0.05),且观察组各项指标均优于对照组(P＜0.05)。Hcy、MDA、斑块面积、不稳定斑块变化值与丁苯酞联合降脂呈正相关,而与强化降脂的相关性更高（P＜0.05）。观察组预后良好率明显优于对照组（P＜0.05）。结论: 丁苯酞联合阿托伐他汀强化降脂治疗急性脑梗死的效果明显,可有效改善患者炎性反应和氧化应激状态,有利于促进神经功能恢复和抑制动脉斑块形成。     

丁苯酞联合奥拉西坦治疗急性脑梗死后认知障碍的疗效观察

摘 要 目的：探讨丁苯酞联合奥拉西坦治疗急性脑梗死后认知障碍患者的疗效及对事件相关电位P300和侧支循环的影响。方法: 急性脑梗死后认知功能障碍患者108例随机分为两组,每组54例。在常规治疗基础上,对照组加用奥拉西坦胶囊治疗,观察组加用奥拉西坦胶囊和丁苯酞软胶囊治疗。两组患者均连续治疗14 d。比较两组治疗后总有效率和侧支循环开放率,以及两组治疗前后中国脑卒中临床神经功能缺损程度评分量表（CSS）评分、血清神经元特异性烯醇化酶水平、蒙特利尔认知评估量表（MoCA）评分、事件相关电位P300潜伏期和波幅变化。结果: 观察组治疗后总有效率为88.9%,显著高于对照组的70.4%(P＜0.05)。与治疗前比较,两组治疗后CSS评分均降低（P＜0.05）,而观察组降低幅度明显大于对照组（P＜0.05）;观察组治疗后MoCA总分和记忆力得分均明显高于本组治疗前和对照组治疗后(P＜0.05),而对照组治疗前后MoCA总分和各单项得分无明显变化(P＞0.05)。观察组治疗后事件相关电位P300潜伏期明显缩短,波幅明显升高,与本组治疗前及对照组治疗后比较,差异有统计学意义(P＜0.05),而对照组治疗前后无明显变化(P＞0.05)。观察组治疗后侧支循环开放率明显高于对照组(P＜0.05)。结论: 丁苯酞联合奥拉西坦对于急性脑梗死后认知功能障碍的疗效确切,可有效改善患者神经功能缺损和纠正事件相关电位P300异常,有利于侧支循环的建立。     

阿替普酶联合丁苯酞治疗急性缺血性脑卒中疗效观察

摘 要 目的：观察阿替普酶联合丁苯酞治疗急性缺血性脑卒中的临床疗效和安全性。方法: 急性缺血性脑卒中患者108例随机分为观察组和对照组各54例。两组均给予控制血糖、血脂、血压等常规治疗,在此基础上对照组给予阿替普酶溶栓治疗,观察组在对照组基础上再加用丁苯酞氯化钠注射液治疗。疗程均为14 d。比较两组的临床疗效、美国国立卫生院卒中量表 (NIHSS) 评分、日常生活能力得分及药品不良反应发生情况。结果: 观察组治疗总有效率为94.4%,明显高于对照组的81.5%(P<0.05)。治疗7 d,14 d后,两组NIHSS评分均较前明显降低(P<0.05),生活能力Barthel指数得分则较前明显升高(P<0.05);且观察组两项评分均优于对照组同时点 (P<0.05)。两组脑出血及总不良反应发生率比较,差异均无统计学意义（P＞0.05）。结论: 阿替普酶联合丁苯酞治疗急性缺血性脑卒中,能有效改善患者的神经功能,提高日常生活能力,安全有效,值得临床推广。     

一种中草药组方对裸鼠皮肤衰老的影响研究

摘 要 目的：考察一种中草药组方对D 半乳糖联合紫外线（UV）光照诱导衰老模型裸鼠皮肤的影响。方法: 每日皮下注射D 半乳糖1 000 mg·kg-1·d-1联合350 ~ 400 nm UV持续照射40 min,连续40 d,诱导亚急性衰老模型。雄性裸鼠随机分为正常对照组,模型组,中草药组方制剂低剂量组（4.16 ml·kg-1）、中剂量组（8.33 ml·kg-1）、高剂量组（16.66 ml·kg-1）,阳性对照组（纽崔莱润妍饮品8.33 ml·kg-1）,每组10只。于造模第11天分别灌胃给药30 d。检测血清中透明质酸,皮肤中透明质酸、羟脯氨酸、总胶原蛋白、Ⅲ型胶原蛋白、弹性蛋白的含量以及皮肤含水量;HE染色观察皮肤形态学改变。结果: 与模型组比较,中草药组方制剂中剂量组皮肤透明质酸含量显著增加（P <0.05）,高剂量组各项生化指标指标均有显著改善（P <0.05或P<0.01）;中、高剂量组各项指标与阳性对照组基本相当（P＞0.05,且低、中、高剂量组间无明显差异（P＞0.05））。中草药组方制剂中、高剂量组皮肤含水量显著增加（P <0.01）,与阳性对照组相当（P＞0.05）;低剂量组含水量明显低于高剂量组与阳性对照组（P＞0.05）。中草药组方制剂中、高剂量组与阳性对照组裸鼠。衰老皮肤的形态明显改善。结论: 该中草药组方具有一定的体内抗皮肤衰老作用。     

核桃健脑片对东莨菪碱诱导记忆障碍小鼠的作用及其机制考察

摘 要 目的：考察核桃健脑片对东莨菪碱诱导记忆障碍小鼠的作用及机制。方法: 小鼠随机分为正常组,模型组,磷脂酰丝氨酸组（40 mg·kg-1）,核桃酶解提取物（66.7 mg·kg-1）组,核桃健脑片低（333 mg·kg-1）、中（667 mg·kg-1）、高（1 333 mg·kg-1）剂量组,连续给药30 d后注射东莨菪碱进行跳台测试,观察潜伏期和错误次数。各组小鼠连续给药第26~30天注射东莨菪碱进行水迷宫测试,观察定位航行测试的逃避潜伏期和空间探索测试穿越原平台次数、到达原平台的时间和在原平台象限游泳的时间;然后取脑组织测定乙酰胆碱酯酶（AChE）、乙酰胆碱转移酶（ChAT）、Na+/K+ ATP酶（Na+/K+ ATPase）的活性,试剂盒测定乙酰胆碱（ACh）、谷氨酸（Glu）、γ 氨基丁酸（GABA）的含量。结果: 核桃健脑片中、高剂量可减少跳台测试中小鼠错误次数（P<0.05）;缩短水迷宫定位航行测试的逃避潜伏期和空间探索测试的到达原平台时间（P<0.05）,增加在原平台象限游泳的时间（P<0.05）和穿越原平台次数。核桃健脑片中、高剂量可降低脑组织的AChE活性和GABA含量（P<0.05）,增加脑组织的ChAT和Na+/K+ ATPase的活性,增加ACh、Glu的含量（P<0.05）。结论: 核桃健脑片中、高剂量可改善东莨菪碱诱导记忆障碍小鼠的学习记忆,其作用机制与调节ACh的代谢,调节Glu与GABA的比例,增加Na+/K+ ATPase的活性有关。     

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.     

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.     

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.