苦物质引起去甲肾上腺素预收缩的大鼠主动脉平滑肌舒张的作用机理研究

为研究苦物质舒张预收缩的大鼠胸主动脉平滑肌的作用机制,以测定肌张力为主要手段,结合多种细胞信号通路阻断剂研究了苦物质的作用通路.结果表明:苦物质对于去甲肾上腺素介导的大鼠胸主动脉的收缩具有高效、快速的舒张作用,此舒张作用与IP3受体和L型钙通道的阻断密切相关.故以氯喹和苦精为代表的苦物质因对血管平滑肌具有良好的舒张作用,有望成为针对高血压等血管相关疾病的新的治疗药物.     

酮替酚和氯喹合并作用对约氏疟原虫抗性株红内期超微结构的研究

酮替酚作用下约氏疟原虫抗性株的超微结构变化与约氏敏感株相似,都表现为有髓鞘状的多层膜结构;而酮替酚和氯喹合并作用下的抗性株有明显不同于单独酮替酚和氯喹作用下的变化:大量类似粗面内质网结构的同心圆排列。     

酮替酚和氯喹合并作用对约氏疟原虫抗性株红内期超微结构的研究

酮替酚作用下约氏疟原虫抗性株的超微结构变化与约氏敏感株相似,都表现为有髓鞘状的多层膜结构;而酮替酚和氯喹合并作用下的抗性株有明显不同于单独酮替酚和氯喹作用下的变化:大量类似粗面内质网结构的同心圆排列。     

The effect of monensin and chloroquine on the endocytosis and toxicity of chimeric toxins

The toxicity of two conjugates containing ribosome-inactivating proteins (RIPs, i.e. saporin and ricin-A chain x-linked to transferrin) has been measured on a prostatic cancer line (PC3) naturally overexpressing the transferrin receptor, in the presence of monensin and chloroquine. This paper investigates whether the increased toxicity of Tf-RIPs induced by monensin and chloroquine may be due to alterations of the normal endocytotic pathway of the complexes mediated by the transferrin receptor. Monensin, besides inducing alkalinization of normally acid intracellular compartments, causes an accumulation of the receptor-bound Tf-RIP in a perinuclear region contiguous to the cisternae of the trans-Golgi network. Chloroquine, though increasing the intracellular pH, seems not to modify the endocytotic pathway of these chimeric molecules. We believe that the enhanced toxicity of the Tf-RIPs may be related to intracellular alkalinization (i.e. endosomal or lysosomal pH) rather than to the effects on the recycling of transferrin receptor-bound toxins. We conclude that the efficacy of chimeric toxins may be modulated not only by the carrier used for their engineering but also by addition of drugs able to influence the stability and activation of the toxins inside the cell. Received 22 December 1997; received after revision 30 March 1998; accepted 15 May 1998     

食蟹猴疟原虫和猪尾猴疟原虫红外期的比较研究

用大量食蟹猴疟原虫子孢子(2.1×10~6)和猪尾猴疟虫子孢子(9.53×10~6)各经股静脉接种一猕猴。前者在接种子孢子后第7天,后者在第8天分别出现首次原虫血症。两猴皆用氯喹(10mg/kg)连续5天作胃管灌服,以清除血中原虫。食蟹猴疟原虫经氯喹治疗后出现3次复发,时间分别为子孢子接种后30,56和155天。每次复发均用上述剂量的氯喹作同样的治疗。在猪尾猴疟原虫则在第1次氯喹治疗后一直无复发出现。用间接荧光抗体染色(IFAT)和吉氏染色法在食蟹猴疟原虫子孢子感染后第7天和62天的猴肝切片中均找到典型的休眠体,而在感染猪尾猴疟原虫第8天的肝切片中,只查到发育成熟的裂殖体而无休眠体。实验结果进一步证实,疟疾“复发”是“休眠体”经过一段时间蛰伏后发育成裂殖子所引起的。     

硫酸氯喹的精制工艺改进

研究了乙醇、异丙醇和丙酮等溶剂对硫酸氯喹成品性能（色泽、澄清度、熔点、晶形）和收率的影响，发现单独以乙醇或异丙醇为重结晶溶剂时，所得成品的晶形和澄清度良好，收率也高，但色泽泛绿，熔点不稳定；单独以丙酮为重结晶溶剂时，所得成品的色泽良好、熔点稳定，但晶形和澄清度差，收率低。为克服单一溶剂的缺点，采用乙醇-丙酮混合溶剂重结晶硫酸氯喹，发现用V(乙醇)：V（丙酮）=1：4的混合溶剂重结晶硫酸氯喹，所得成品色泽、澄清度和晶形良好，熔点稳定，符合BP93要求，收率也很理想。