用大肠杆菌CM89菌株对三种化学物抗突变作用的研究

本文以 E.coli CM891为靶细胞,用细菌内抗突变作用模式研究了肉桂醛,鞣酸,二烯丙三硫的抗4NQO 突变性及其作用机制。含质粒 pKM101的 CM891的高抗株(抗50μg/ml 氨苄青霉素)能提高该菌株的自发突变率和4NQO 诱发的突变率以及对鞣酸的杀伤抗性。肉桂醛的抗突变性不依赖质粒 pKM101效应,但与暂时性生长延搁有关。鞣酸及二烯丙三硫的抗突变机制可能包括质粒 pKM101介导的易误修复。上述三种化学物中每二种联合应用均显示抗4NQO 突变性的协同效应及对靶细胞的毒性杀伤作用。     

强化婴幼儿奶粉中叶酸的测定

强化叶酸的奶粉在0.05M K_2HPO_4缓冲液中,经均质,调pH4.5,15000g离心20分钟,其清液调pH4.0,进行CGS树脂离子交换层析,用10ml KClK_2HPO_4洗脱,调pH7.0,进行HPLC测定,采用300x3.9mm ODS反相柱,移动相0.05M K_2HPO+MeOH(91+9),流速1ml/分,紫外检测器波长285nm,灵敏度0.0050D。方法相对标准偏差为±3.3％,回收率为87％,最小检测量为0.02μg/ml。     

氨甲环酸中顺式异构体的高效液相色谱法测定

本文采用高效液相色谱法测定氨甲环酸中的顺式异构体含量。先用衍生化试剂３，５－二硝基苯酰氯预处理氨甲环酸，然后通过ＨＰＬＣ，以喹啉为内标，ＹＭＣ－ＰａｃｋＡＭ－３０２ＯＤＳ为色谱柱，甲醇－０．０２ｍｏｌ／Ｌ醋酸铵溶液（４：７）为流动相，在２５４ｎｍ波长处检测，顺式异构体在１～２．５μｇ／ｍｌ范围内线性关系良好（ｒ＝０．９９６１），最低检测限为０．０２％。     

Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats

The effects of glycyrrhetinic acid (GA), an aglycon of glycyrrhizin extracted from the roots of Glycyrrhizae radix, on puromycin aminonucleoside (PA) nephrosis were studied in rats. Urine protein excretion in female rats (130g–150g) receiving PA (50 mg/kg) alone was significantly elevated on the 2nd day after injection of PA and reached a peak on the 14th day. Urinary protein on the 14th day was reduced to 74% in animals treated with GA (20 mg/kg) starting on the 2nd day after injection of PA. The increase in serum cholesterol and the decrease in serum protein were also suppressed by GA. Observation by electron microscopy revealed that the degree of abnormality in glomerular epithelial cells, i.e. loss or fusion of foot processes, was lower in the rats treated with GA after PA injection than in the rat treated with PA alone. Moreover, pretreatment with GA did not suppress urinary protein excretion but when it was given at the same time as PA and after PA a significant decrease in urinary protein excretion was observed. Correspondence to: H. Abe at the above address     

Inhibition of GABA-gated chloride channel function by arachidonic acid

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.     

Sialic acid concentrations in the urine of men with and without renal stones

Summary It has been suggested that urinary sialidase may play a role in the formation of renal stones. The present study was therefore undertaken to compare spectrophotometrically the different types of sialic acid concentrations and sialidase activities in fresh first morning urine specimens of men (21–65 years) with (13) and without (9) calcium oxalate renal stones. Although the free urinary sialic acid concentrations of the two groups of men were statistically about the same (P=0.0614), the total (P=0.003) and bound (P=0.0012) urinary sialic acid concentrations differed significantly. Both the total and bound sialic acid concentrations were lower in the urine specimens of the stone patients than in their healthy counterparts. This decrease in urinary sialic acid concentrations was firstly thought to be the result of elevated breakdown enzymes of sialic acid, which would favour the production of pyruvate. However, spectrophotometric determinations of the endogenous pyruvate concentrations of the two types of urine specimens did not differ significantly (P=0.0708). Secondly, the decrease in total urinary total sialic acid concentration of stone patients, could be attributed to less sialic acid synthesis or less renal excretion. Therefore, the same experiments were repeated using serum of 13 patients and 9 healthy men. Conversely, the total (P=0.4425) and bound (P=0.2850) serum sialic acid concentrations were found to be similar in the two types of subjects. However, the free serum sialic acid concentration of stone patients was significantly lower than in the healthy subjects (P=0.0062). This phenomenon is also reflected in the average ratio for serum free: bound sialic acid in healthy and stone patients, 1:7.9 and 1:18.7 respectively (P=0.0009). The lower free serum sialic acid concentration may lead to lower renal excretions of sialic acid. This may explain the decrease in total urinary sialic acid concentration in stone patients. The lower bound urinary sialic acid concentrations in patients was also reflected in the urinary free: bound sialic acid ratio for healthy (1:2.3) and stone patients (1:1.3). The difference between these two groups of men was highly significant (P=0.0001). This phenomenon might be explained by the urinary sialidase activities, which was spectrophotometrically determined at 334 nm at 37°C of 11 patients with stones and 17 healthy men. The ages of both groups of men were the same (P=0.326). An increase in urinary sialidase activity was observed with the stone patients (P=0.00001) when compared to specimens of healthy men. This might explain the decrease in urinary bound sialic acid concentration of the stone group. It seems from these results that the urinary concentration of sialic acid and the activity of urinary sialidase, may play a role in the pathogenesis of the multifactorial disease, urolithiasis.     

胎盘组织液氨基酸的含量测定及层析鉴别

本文采用层析法进行鉴定,用氨基酸分析仪测氨基酸的含量,为胎盘组织液的质量标准提供可靠依据。本法准确率为99%。     

Pharmacokinetics of a valpromide isomer,valnoctamide, in healthy subjects

Summary The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.     

Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers

Summary In order to investigate possible effects of smoking and drinking on the metabolism of toluence in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift-end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits.