维那利酮的诱变试验研究

作者应用鼠伤寒沙门氏菌回复突变试验,小鼠骨髓红细胞微核试验及CHL细胞染色体畸变试验,对维那利酮(OPC-8212)的诱变性进行了试验研究,其结果均为阴性。说明 OPC-8212不诱发原核细胞基因突变,也不会导致体内、体外染色体畸变,是一种安全可靠的强心剂。     

3，4－二甲氧基苯甲酰哌嗪衍生物的合成及其正性肌力作用初探

作者对新型正性肌力药维司力农（Ｖａｓｎａｒｉｎｏｎｅ，即ＯＰＣ－８２１２）结构进行改造，合成了十二个３，４－二甲氧基苯甲酰哌嗪新衍生物（ＴＭ－１～ＴＭ－１２），其结构经红外光谱、质谱、核磁共振氢谱及元素分析确证。将目标化合物ＴＭ－１、ＴＭ－２及中间体（３）（ＶＰＡ）作药理试验，结果显示它们对豚鼠离体心房均有正性肌力作用，其中ＯＰＣ－８２１２及ＶＰＡ与二甲亚砜对照有显著性差异（Ｐ＜０．０５）。进一步的药理试验正在进行中。     

新型正性肌力药物维纳利酮对离体犬心室乳头肌细胞...

This study adopted intracellular microelectrode technic to observe the effect of OPC-8212 (Vesnarinone) on intracellular potential of isolated canine ventricular papillary muscle. The record and data processing were completed by computerized intellective instrument designed by ourselves. The results of intracellular record in 14 canine ventricular papillary muscle showed no significant change in the resting potential (RP), amplitude of action potential (APA) and maximum depolarize velocity of 0 phase (Vmax). But significantly increased whole duration of action potential (APT). The duration of repolarization to 1/3 (APD 1/3) and to 2/3 (APD 2/3) significantly increased too. The plateau phase raised. These results suggest that K+ permeability at resting myocardiac cell membrane may have not been effected by OPC-8212. Activation of the fast sodium channel may have not been effected too. The results of our studies also suggest that inward flow of Ca2+ increased. The delayed outward K+ (Ik) and the inward, rectifying K+ current (Ik1) possible decreased. Thus, the OPC-8212 might become a nonglucoside and noncatecholamine new positive inotropic drug.     

新型正性肌力药物维那利酮对犬的循环呼吸功能的影响

作者探讨了我校合成的新型强心药维那利酮(OPC-8212)对犬循环和呼吸的效应。实验结果:OPC-8212使犬颈总动脉流量显著增加;对血压、心率和呼吸三项指标均无明显影响。表明OPC-8212在整体动物心脏具有正性肌力效应而不具频率效应。有可能成为一种理想的新型强心剂。     

新型正性肌力药牧维那利酮对犬的循环呼吸功能的影响

The purpose of this study was to investigate the influences of vesnarinone, newly synthesized in the School of Pharmacy, West China University of Medical Sciences in 1985, on the circulatory and respiratory functions of dogs. Eight dogs were anesthetized with 3% sodium pentobarbital. Vesnarinone (2 mg/kg), dimethyl sulphoxide (the solvent which was needed to prepare solution of OPC-8212), and 0.9% NaCl (normal control) was given separately according to the arrangement of Latin square. The ECG, blood flow, blood pressure and respiration were measured and recorded for 1-15 minutes. Vesnarinone increased the blood flow in the common carotid artery with no significant changes in blood pressure, heart rate, or respiration. These results suggest that OPC-8212 has positive inotropic effect but no effect on the heart rate in anesthetized dogs.     

新型正性肌力药物维纳利酮对离体犬心室乳头肌细胞内电位的影响

作者采用微机化的智能仪记录及处理资料,研究了我校新合成药维纳利酮(又名OPC—8212)对14例犬心肌细胞内电位的影响。结果:静息电位(RP)、动作电位振幅(APA)和0期去极最大速度(V_(max))在维纳利酮作用前后均无显著差异,而动作电位全程(APT)、动作电位复极至1/3时程(APD1/3)及复极至2/3时程(APD 2/3)均有明显增加。平台期有所抬高。提示维纳利酮并不影响心肌细胞膜静息时的K~+通透性,也不影响快Na~+通道的激活和开放数目。而有可能增加Ca~(2+)通道的开放时间、增加Ca~(2+)内流;也可能同时具有减弱延迟外向钾电流(Ik)和内向整流钾电流(Ik_1)的作用。因此维纳利酮有可能成为一种很有希望的非甙、非儿茶酚胺类的新型正性肌力药物。     

实验室室间质评染色体检测水平效果分析

目的：分析参加美国病理学会（CAP）室间质评的能力比对检验（PT）后,染色体检测水平的变化。方法分析2011～2014参加CAPPT的结果,并根据CAP评审结果,得出该实验室细胞遗传学染色体质控测试的准确率,并通过分析该实验室参加CAP前后的染色体条带水平、异常检出率及染色体检测失败率,评估CAP室间质评项目对提高该实验室染色体检测水平的作用。结果2011～2014年该实验室参加CAPPT测试10次,共分析病例59例,判断染色体核型正确率为100％,核型描述正确率为95．1％。该实验室临床病例染色体检测结果显示：外周血染色体的异常检出率为18．9％,骨髓染色体的异常检出率为25．9％,初诊白血病异常率为66．8％;外周血染色体及骨髓染色体检测的失败率分别为0．5％、5．0％;参加CAP后,外周血及骨髓染色体检测失败率均下降,染色体条带平均水平均提高,与参加CAP前比较差异均有统计学意义（P＜0．01）。结论参加高水平的室间质评项目可以提高细胞遗传学染色体检测的临床分析水平。     

普鲁兰多糖对小鼠的致突变性实验研究

目的研究普鲁兰多糖的潜在致突变性。方法采用小鼠骨髓细胞微核试验、小鼠骨髓细胞染色体畸变试验、小鼠精子畸形试验进行观察。结果骨髓细胞微核试验、骨髓细胞染色体畸变、精子畸形试验均为阴性结果。结论普鲁兰多糖在所试条件下无潜在的致突变作用。     

氨利酮与甲腈吡酮的诱变性试验研究

The mutagenicity of domestic new drugs amrinone and milrinone were studied by Ames test, micronucleus test of mouse bone marrow and chromosome aberration assay in CHO cells. The results were as follows: neither amrinone nor milrinone was mutagenic in the Ames test; in chromosome aberration assay, both gave positive results; in mouse micronucleus test, amrinone gave a positive result when mice were exposed to 0.8 LD50 dose, but milrinone gave a negative result. These results suggested that amrinone and milrinone did not induce gene mutation, but amrinone induced chromosome damage both in vitro and in vivo, while the chromosome-damaging activity of milrinone in vitro may be minimized by biodetoxication in vivo.     

文蛤肉水解液的致突变性研究

目的 评价文蛤肉水解液的致突变性，为文蛤的开发利用提供实验数据。方法 采用Ames试验、小鼠嗜多染红细胞骨髓微核试验和CHL细胞体外染色体畸变试验3项致突变性试验，检测文蛤肉水解液有无致突变作用。结果 Ames试验中文蛤肉水解液各剂量组回变菌落数均在正常范围内，均未超过自发回变菌落数的2倍，在加与不加S9时5株试验菌株结果为阴性。CHL细胞体外染色体畸变试验，文蛤肉水解液各剂量组的染色体畸变率与阴性对照组比较，差异无统计学意义（P>0.05），结果为阴性。小鼠骨髓微核试验，各剂量组的微核率与阴性对照组比较，差异无统计学意义（P>0.05），结果为阴性。结论 在本试验条件和范围下，文蛤肉水解液未见潜在的致突变作用。