依达拉奉防治缺血性脑损伤研究的新进展

近年来,依达拉奉脑保护作用的研究取得了很大进展,尤以对缺血性脑卒中和新生儿缺血缺氧性脑病的防治研究最为深入,而联合治疗策略也得到了广泛的重视.本文就近5年这些热点研究的新进展进行综述.     

氨乙基异硫脲对大鼠离体心脏冠脉结扎后再灌期心律失常与细胞动作电位的作用

用Langendorff方法与微电极技术研究自由基清除剂氨乙基异硫脲(AET)对离体大鼠心脏冠脉结扎后再灌期心律失常与细胞动作电位的作用。AET(0.001～1mmol/L)使室颤和室速发生率明显下降,使正常窦性心律时间增加。浓度为0.01～1mmol/L的AET可使不可逆室颤发生率下降为零。冠脉阻塞再灌损伤使缺血中心区心肌动作电位波形异常,APA,RP,V_(max)各参数下降。AET(0.1mmol/L)可使异常波形动作电位显著减少。     

Cholesterol and atherosc lerosis

Cholesterol is an essential component of cellular membranes, but when present in excess in the circulation, can be deposited in the arterial wall, leading to the formation of atherosclerotic lesions. The principal plasma carrier of cholesterol, low density lipoprotein (LDL), is removed from the circulation by LDL receptors in the liver. This process plays a critical role in regulating plasma LDL levels. The unique structure and composition of the LDL particle makes it particularly susceptible to modification by oxidative reactions. Current evidence suggests that the production of oxidised LDL in the intima, and the removal of oxidised LDL particles by scavenger receptors on macrophages, play a central role in the development and progression of atherosclerotic lesions.     

The protective effect of vitamin E on cerebral ischemia

Using the "canine model of the completely ischemic brain regulated with a perfusion method," the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia.     

人SR-AI转基因小鼠模型的主要形态学特性、血液学指标和血脂水平的研究

目的明确人SR-AI转基因小鼠的一些形态、脏器、血液学和血浆脂质参数,为人SR-AI转基因小鼠模型的应用提供相关依据.方法用游标卡尺和电子称量天平测量人SR-AI转基因小鼠的吻长、眶间距、体长、尾长及12个脏器系数并与C57BL/6J小鼠进行比较分析;用SysmexK-4500型全血自动多参数血液分析仪检测其血液学指标;并用酶法分别测定血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇含量.结果人SR-AI转基因小鼠外部形态指标和脏器系数与C57BL/6J小鼠比较差异没有显著意义(P>0.05);转基因小鼠的各项血液学指标无明显改变,血脂蛋白成分的改变亦未显示统计学意义(P>0.05),甘油三酯的浓度略有增高(P<0.05).结论人SR-AI转基因小鼠的外部形态指标、脏器系数及各项血液学指标均无明显改变,适合用作动脉粥样硬化模型的研究.     

Charge-based interactions of mammalian sperm with oocytes: inhibition of fertilization of mouse oocytes by ligands of macrophage scavenger receptor(s)

Objective: To determine whether anionic ligands for the macrophage scavenger receptor inhibit the fertilization of mouse oocytes by mouse spermatozoa.

Design: In vitro study of sperm binding and two-cell embryo formation in the presence of scavenger receptor ligands. Sperm-oocyte interaction may be mediated by sulfated sugars. In this study, we tested other nonsulfated anionic ligands for the scavenger receptor for their ability to affect fertilization. The only common feature of these ligands is their anionic nature.

Setting: Oocytes and sperm from mice were used.

Main Outcome Measure(s): Binding of sperm to oocytes and subsequent formation of two cell embryos were determined.

Result(s): Fucoidin, polyinosinic acid, oxidized low-density lipoprotein, acetyl low-density lipoprotein, and malondialdehyde-modified LDL inhibited the binding and fertilization of mouse sperm to mouse oocytes. Addition of fresh sperm to oocytes previously treated with sperm in the presence of these agents restored the binding and fertilization.

Conclusion(s): These results show that charge-based interactions analogous to the interactions of the scavenger receptor with its ligands may play an important role in mammalian fertilization.     

富勒烯和富勒醇的生物学和生物医学应用研究

介绍富勒烯C60和富勒醇C60(OH)n(n=6-24)的生物学和生物医学应用。C60可抑制半胱氨酸蛋白酶和丝氨酸蛋白酶的活性，它以强憎水作用结合于HIVP(人体免疫缺损病毒蛋白酶)的空穴，可抑制HIVP的活性，可使氧分子转化为活性氧和超氧自由基，切割DNA。富勒醇可抑制小鼠大动脉平滑肌细胞生长，但促进HL-60细胞的生长代谢。C60能清除自由基，在光照和避光条件下具有诱导癌细胞凋亡的能力。     

依达拉奉的合成

用苯肼和乙酰乙酸乙酯在亚硫酸氢钠参与下于水中回流反应2h制得自由基清除剂依达拉奉,收率83%.方法操作简单,成本低.     

The Effect of Inert Atmospheric Packaging on Oxidative Degradation in Formulated Granules

No HeadingPurpose. Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation.Methods. Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40°C. The oxidative degradation was quantified as a function of time.Results. The results clearly show dependence of oxidative degradation on headspace oxygen concen-tration, relative humidity, drug loading and time.Conclusions. The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.     

依达拉奉治疗急性脑梗死的临床观察

目的：探讨依达拉奉对急性脑梗死治疗的临床疗效。方法：将130例急性脑梗死患者分为依达拉奉治疗组和对照组（常规治疗）,每组65例,两组均给予血小板聚集抑制剂、改善微循环药物和神经营养药物等基础治疗。将两组患者治疗前后神经功能缺损评分（NIHSS）之差和血液动力学指标进行对比分析。结果：治疗前与治疗后神经功能缺损评分之差两组差异有统计学意义（P〈0.05）,血流动力学指标中除纤维蛋白原外差异无统计学意义（P〉0.05）。结论：在脑梗死急性期依达拉奉对缺血大脑组织具有保护作用,对血流动力学无明显影响,合并出血的风险小。